83  Trabeculectomy-Related
Corneal Complications
MAGDY A NOFAL and FATHI F EL SAYYAD
Summary
Corneal complications after trabeculectomy operations may
include:
■ Corneal epitheliopathy due to anti-metabolites use.
■ Corneal endotheliopathy and corneal decompensation.
■ Corneal topographic changes and corneal astigmatism.
■ Intracorneal bleb dissecting.
■ Descemet’s membrane detachment.
■ Corneal epitheliopathy due to releasable suture techniques.
■ Dellen formation.
■ Corneal ectasia and interface fluid syndrome in laser in situ
keratomileusis.
■ Corneal graft rejection after trabeculectomy.
■ Descemet’s stripping automated endothelial keratoplasty
(DSAEK) and trabeculectomy.
■ Corneal complications after trabeculectomy with anti-VEGF.
■ Corneal blood staining.
The key to surgical success is for the surgeon to be alert and to
be able to identify and address any problem promptly.
Introduction
The characteristics of clarity and curvature of the cornea
are the most important principal requirements for its physi-
ologic function. The highly specialized structure of the
cornea can be altered as a result of performing trabeculec-
tomy, especially if antimetabolites are being used. Nonethe-
less, a successful final outcome of trabeculectomy may
often be achieved in spite of the occurrence of corneal
complications.
Persistent corneal edema significantly predicted vision
loss in an analysis of long-term complications of trab-
eculectomy though this was more common after aqueous
shunts.1 Trabeculectomy-related corneal complications can
also be adversely affected by the presence of a pre-existing
corneal disease, severity and chronicity of intraocular pres-
sure and prior intraocular procedures.
In this chapter we will review the corneal complications
associated with trabeculectomy operations. Some of these
complications have been recognized only recently, such as
complications related to the use of antivascular endothelial
growth factor (anti-VEGF) and those related to Descemet’s
stripping automated endothelial keratoplasty (DSAEK) and
intracorneal bleb dissection.
Post-Trabeculectomy Corneal
Epitheliopathy and
Endotheliopathy
The healthy and intact corneal epithelium and tear film
play a crucial role in the maintenance of the cornea’s
smooth surface. The corneal endothelium does not prolifer-
ate in humans; its most important physiological function is
to regulate the water content of the corneal stroma by the
ion transport system. Corneal endothelial complications
are commonest in patients with aqueous shunts (8–29% of
patients). With the exception of aqueous shunts, glaucoma
procedures are not known to result in progressive endothe-
lial cell loss.2
The use of antimetabolite agents both during and after
trabeculectomy has greatly increased the success rate of the
operation. The two agents commonly used in current glau-
coma filtration surgery are 5-fluorouracil (5-FU) and mito-
mycin C (MMC). 5-Fluorouracil appears to be toxic to
fibroblasts while sparing vascular endothelial cells, whereas
mitomycin C is cytotoxic for both cell types. The efficacy
of mitomycin C in reducing the intraocular pressure
appears to be greater than that of 5-fluorouracil. There is
also an increase in both the frequency and magnitude of
complications associated with mitomycin C. Corneal and
conjunctival epithelial toxicity, manifested as punctate epi-
thelial erosions, corneal epithelial defects, and/or abra-
sions, and primary conjunctival wound leaks, are the most
common complications of postoperative subconjunctival
5-fluorouracil injection3 (Fig. 83-1).
Methods for mitomycin C application during glaucoma
filtering surgery have varied considerably. A greater IOP
reduction after trabeculectomy can be achieved when
adjunctive mitomycin C is applied simultaneously under
both scleral and conjunctival flaps. Subscleral application
should be abandoned in cases where a micro-perforation is
suspected, as it may lead to irreversible endothelial damage.4
Application time, method of application, and the concen-
tration of the drug are important factors that can signifi-
cantly affect the amount of the drug applied.
The corneal epithelium plays a very important role in
maintaining the health of the corneal surface. A cornea
with chronic epithelial loss resists collagenolysis poorly,
which may lead to corneal melting and perforation. Corneal
complications can be minimized by decreasing the
contact between the antimetabolite agent and the ocular
surface either by using the subconjunctival injection
829
830 SECTION 11  •  Trabeculectomy
Figure 83-1  Large corneal epithelial defect stained with fluorescein
following multiple postoperative subconjunctival 5-FU injections.
technique or by administering a low dose of 5-fluorouracil
or mitomycin C.5,6
The frequent application of topical corticosteroids is a
common practice after glaucoma filtering surgery. Corticos-
teroids are known to enhance serious complications such
as persistent epithelial defects, corneal melting, bacterial
ulceration, corneal perforation, and keratinized corneal
plaque with underlying sterile stromal infiltrate.7 Therefore,
the combination of 5-fluorouracil and topical corticoster-
oids in patients with pre-existing corneal epithelial disease
creates a great potential for these complications to occur. If
corneal epitheliopathy develops, consideration should be
given to cessation or reduction of either the 5-fluorouracil
or the topical corticosteroid therapy, or both. A broad-
spectrum topical antibiotic should be initiated.
Eyes with limited limbal stem cell populations, such as in
Stevens–Johnson syndrome, ocular pemphigoid, and alkali
injury, are vulnerable to this toxic effect and should not
receive subconjunctival 5-fluorouracil, or perhaps any
antimetabolite therapy, for fear of permanently reducing
the limbal stem cell pool.
Pre-existing corneal epithelial edema also has been asso-
ciated with serious bacterial corneal infections, thinning,
and corneal melting in eyes that received 5-fluorouracil
after filtration surgery. Limbal stem cell deficiency can occur
as a late complication for patients receiving 5-fluorouracil
after glaucoma filtering surgeries. Partial limbal stem cell
deficiency can be treated with amniotic membrane trans-
plantation alone, whereas limbal transplantation can be
considered for total limbal stem cell deficiency to restore the
corneal surface integrity and vision.
Infectious crystalline keratopathy is a condition usually
associated with bacterial or fungal organisms. Infectious
crystalline keratopathy has also been reported subsequent
to glaucoma filtering surgery with and without using post-
operative 5-fluorouracil8 as well as in eyes maintained on
long-term use of low doses of topical steroids after
trabeculectomy.9
Noninfectious transient crystalline keratopathy has also
been reported following trabeculectomy without the use of
subconjunctival 5-fluorouracil. This condition may present
with intrastromal corneal crystalline deposits a few
days after postoperative subconjunctival injection of
5-fluorouracil. The deposits disappear a few days later
without treatment. Subconjunctival 5-fluorouracil injec-
tion should be included in the differential diagnosis of non-
infectious crystalline keratopathy.10
Corneal and conjunctival epithelial erosions due to
5-fluorouracil can be minimized by using a long injection
track and a viscoelastic to tamponade the 5-fluorouracil
and prevent tear film leakage as well as reducing the dose
and increasing contact time between the eye surface and
the antimetabolite agent. Additionally, care should be taken
during subconjunctival injection of antimetabolites or nee-
dling with antimetabolites for encysted blebs, particularly
in soft eyes, as intraocular penetration can cause irreversi-
ble damage if the antimetabolite agent is injected inadvert-
ently into the eye.
In cases of inadvertent administration of antimetabolites
in the anterior chamber, anterior chamber wash-out can be
performed to prevent endothelial damage. However, severe
corneal edema may develop. The corneal edema may resolve
completely after 6 months. However, increased endothelial
cell pleomorphism may be noticed permanently.11,12
Punctal occlusion using collagen punctal plugs optimizes
the tear film and corneal wetting. The use of preservative-
free artificial tears is also helpful. Beckman et al. also
reported that bandage contact lens application increased
comfort and decreased inflammation.13
Trabeculectomy-related corneal complications are not
limited to the corneal epithelium only. Corneal endothelial
changes have been reported after uncomplicated trab-
eculectomy with and without antimetabolites. Specular
microscopic studies showed that there is a significant differ-
ence in the central corneal endothelium count after uncom-
plicated trabeculectomy with no antimetabolites when
compared with similar patients who have no surgical treat-
ment. Some studies reported a 6.35% decrease in the central
corneal endothelium density in 65 to 75-year-old patients
with chronic open-angle glaucoma 3 months after uncom-
plicated trabeculectomy with no antimetabolites.14
Using absolute alcohol to re-epithelialize the bleb epithe-
lium is a newly described technique for the management of
leaking blebs. This technique has the advantage of leaving
the original bleb in place while resurfacing it with the
alcohol, thus minimizing the potential for contraction.
Acute corneal decompensation has also been reported fol-
lowing surgical bleb revision using a large amount of abso-
lute alcohol. Surgeons should be aware of the potential
risks of inadvertent administration of alcohol in the ante-
rior chamber during this procedure.15
Loss of corneal endothelial cells may also occur after
trabeculectomy with adjunctive mitomycin C. In one study,
mitomycin C 0.4 mg/mL produced a central endothelial cell
loss of around 14% within the first 3 months. Severe
damage to the corneal endothelium after a trabeculectomy
with mitomycin C has also been reported in middle-aged
patients. The corneal endothelial cell loss may be caused by
a pre-existing cornea guttata, postoperative flat anterior
chamber, and possibly the accidental intracameral penetra-
tion of mitomycin C. The use of tight sutures on the scleral
flap or nonpenetrating glaucoma surgery may be effective
in preventing a shallow to flat anterior chamber
postoperatively.16
Bullous keratopathy following uncomplicated trabeculec-
tomy with mitomycin C has also been reported. Surgeons

should be aware of these complications and take extra pre-
cautions if the corneal endothelium is compromised before
surgery. In these cases, application of mitomycin C may
have an additional toxic effect on the endothelium and may
result in severe damage to the corneal endothelium, result-
ing in bullous keratopathy.17,18
Postoperative bleb needling with antiproliferative agents
for failed filtering blebs may also be associated with corneal
complications.19 In a recent prospective observational study
of 81 consecutive patients undergoing bleb needling, Roach-
ford and King20 reported one case of corneal decompensa-
tion in a pseudophakic eye after five needlings, and corneal
transplantation was subsequently required. The authors did
not comment on why this complication occurred.
Patients undergoing combined surgical management of
cataract and glaucoma can have the two procedures per-
formed via one site or via two separate sites. Buys et al.21
looked at corneal endothelial density loss and IOP reduction
over a 2-year period in a prospective randomized control
study. There was a significantly lower cell count at 3 and 12
months in the two-site versus one-site group, but this was
no longer significant at 24 months. The authors speculated
that the temporal incision in the two-site approach might
be associated with greater endothelial trauma, whereas the
more posterior scleral tunnel incision used in the one-site
approach might result in less endothelial damage.
Corneal Topographic Changes
and Corneal Astigmatism after
Trabeculectomy
After successful trabeculectomy, patients often complain of
blurred vision. Among other factors, this can be due to
changes in the corneal topography and in corneal astigma-
tism, Studies using computer-assisted corneal topography
showed that complex regional changes occur in the corneal
curvature after uncomplicated trabeculectomy operations.
These changes are not readily detected from alterations in
refraction or keratometry.22,23 Irregular astigmatism also
increases significantly after trabeculectomy, but returns to
the preoperative level 12 months after surgery. These
changes can be sufficiently great to have a significant effect
on visual function in some patients.24
Corneal topographic studies showed that some patients
develop a relative superior corneal steepening, superior flat-
tening, or complex regional changes that do not conform to
either of these patterns. Some patients may develop up to
1.50–2.50 diopters of steepening in the 90° meridian. In
some patients, these topographic changes may last for up to
1 year after surgery. Keratometry appears to be less sensitive
than topographic analysis in detecting the changes induced
by trabeculectomy, and changes in corneal curvature may
be undetectable without topographic analysis.
Micro-trabeculectomy produces smaller and transient
changes in corneal curvature. In micro-trabeculectomy a
2 × 2 mm scleral flap is fashioned and a 0.75 mm internal
ostium is created using the Kelly-Descemet’s membrane
punch.22 Other studies showed that uncomplicated trab-
eculectomy with mitomycin C can also be associated with
long-lasting changes in the corneal curvature and also a
83  •  Trabeculectomy-Related Corneal Complications 831
significant reduction in the axial length. Eyes with higher
preoperative IOP appear to have a greater decrease in axial
length after trabeculectomy with mitomycin C. Significant
shortening of the axial length can occur after combined
phacoemulsification–trabeculectomy operations as well.
The mean axial length reduction after combined operation
appears to be significantly larger than the reduction after
cataract operation alone and correlated significantly with
the postoperative IOP. However, despite an alteration of the
axial length and corneal curvature, the refractive outcome
after a combined operation does not differ significantly from
the predicted refraction.25
Non-penetrating trabecular filtering surgeries with and
without implant can also produce significant changes in the
corneal topography. However, average induced astigmatism
was lower in nonpenetrating surgeries than the trabeculec-
tomy surgeries at postoperative months 3 and 6 despite
larger flap size and surgical area.26
Dissecting Bleb
Intracorneal dissection and overhanging of the blebs,
causing astigmatism and reduced visual acuity, are late
complications of trabeculectomy. A recent case report27
with histopathological examination of a dissected bleb
demonstrated loose connective tissue between the limbal
corneal epithelium and Bowman’s layer, suggesting that
the bleb was dissecting into cornea. Surgical management
involves blunt dissection of the overhanging bleb from
the cornea followed by limbal excision (Video 83-1). Dis-
secting blebs often requires removal and refashioning of the
whole bleb (Fig. 83-2A,B).
Detachment/Stripping of the
Descemet’s Membrane
Descemet’s membrane detachment may be associated with
anterior chamber reformation through a paracentesis entry
incision, to treat a flat anterior chamber and hypotony after
a trabeculectomy.28 Large detachments are generally associ-
ated with corneal edema which may be permanent with
significant visual loss. However, large Descemet’s mem-
brane detachment may unexpectedly be associated with a
clear cornea in some cases.
Medical treatment including frequent topical steroids
and hypertonic saline that are used to improve the kerat-
opathy seem to be adequate in many cases and may be
appropriate initial therapy. Some cases resolve spontane-
ously within a few months. However, descemetopexy may
be needed in some patients. SF6 gas injection or a sterile
air bubble may also be successful, but not in all cases. Pen-
etrating keratoplasty may be required if medical treatment
fails29 (Fig. 83-3).
Corneal Complications Related to
Releasable Sutures Techniques
Some surgeons use 10-0 nylon releasable sutures to close
the scleral flap. If the loose end of the slip knot is not buried
832 SECTION 11  •  Trabeculectomy

Figure 83-4  Windshield-wiper keratopathy with releasable sutures.

A in the cornea it can cause irritation due to a windshield-

wiper effect with consequent keratopathy and potential
infectious keratitis, especially if an antimetabolite is used.
To avoid such a complication, the releasable suture should
be buried superficially in the cornea. In a retrospective
review of 154 trabeculectomies with releasable sutures
technique, corneal complications included a typical
windshield-wiper keratopathy in 18 eyes, failure to release
the suture in 13 eyes, and epithelial abrasion in 6 eyes30–33
(Fig. 83-4).

B
Figure 83-2  (A) Intracorneal bleb dissection involving the whole
cornea. (B) Corneal opacification following blunt dissection of bleb.
Figure 83-3  Stripping of the Descemet’s membrane. (Courtesy of
Ashraf Amayem, MD.)
Dellen Formation
Large blebs causing tear film abnormalities with dellen for-
mation and superficial punctate keratopathy or chronic
epithelial defect may result in some discomfort. The use of
topical steroids during the postoperative period may con-
tribute to dellen formation by inhibiting corneal epithelial
wound healing. The most important predisposing factor in
dellen formation is poor tear film adjacent to the bleb. Arti-
ficial tears and ocular lubricants can be helpful, especially
in patients with abnormal tear film.34 In most patients, the
corneal changes heal uneventfully with medical treatment.
However, in some patients, the dellen may progress to a
deep corneal ulcer, especially in eyes with large filtering
blebs.
Large blebs can be freed by blunt dissection and excision
of the part of the bleb encroaching on the cornea, with or
without conjunctival flap reinforcement. Anis et al.
described a technique for the treatment of large overhang-
ing circumferential blebs. The technique involves separa-
tion of the bleb from the corneal surface by blunt or sharp
dissection. The overhanging portion of the bleb is excised
and a bandage contact lens inserted. The author concluded
that sutureless surgical revision of overhanging filtering
blebs is a safe and effective technique to reduce bleb-related
dysesthesia and improve cosmesis without compromising
filtration function. However, bleb failure is a possible risk
after postoperative surgical revision.35 A conjunctival com-
pression suture with autologous blood is another effective
and simple technique for remodeling the filtration blebs.
The procedure can be performed under topical anesthesia
and does not hinder further bleb surgery, should this be
required36 (Fig. 83-5).

Figure 83-5  Dellen formation with chronic corneal epithelial defect
related to a trabeculectomy with a large bleb.
Trabeculectomy-Related
Complications after   (DSAEK) is a relatively new type of partial-thickness corneal
Refractive Surgery
It is becoming more frequent to do cataract and glaucoma
surgery on patients who have had refractive surgery previ-
ously. Recently, corneal complications related to glaucoma
filtration surgery have been reported in patients with previ-
ous refractive corneal surgery. Kang et al. described a case
of a 69-year-old man who developed stromal edema and a
pocket of fluid in the laser in situ keratomileusis (LASIK)
interface wound after a trabeculectomy operation compli-
cated with acute endothelial cell loss. The patient received
seven postoperative injections of 5-FU, which could have
had an additional direct toxic effect on the corneal endothe-
lium. The patient eventually required a penetrating kerato-
plasty. It should be known that even though LASIK does not
cause endothelial cell damage, any condition that disturbs
endothelial cell function may precipitate interface fluid
syndrome.37,38
Bilateral superior corneal ectasia has also been reported
in a 45-year-old patient 15 years after an uncomplicated
trabeculectomy with mitomycin C operation. The authors
of the report speculated that the corneal ectasia might have
been induced by bleb compression or might have been
caused by a late toxic complication of mitomycin C, which
penetrated the corneal stroma during the operation and
caused this episode. Prolonged impairment of peripheral
corneal epithelial barrier function after the trabeculectomy
has been reported previously. There is also speculation that
the corneal ectasia may also have been a coincidental
finding.39,40
Corneal Graft Rejection after
Trabeculectomy
Elevation of intraocular pressure following penetrating
keratoplasty is a serious clinical complication. Trabeculec-
tomy with mitomycin C has been used with good results for
glaucoma following keratoplasty when controlling ocular
83  •  Trabeculectomy-Related Corneal Complications 833
pressure following keratoplasty is difficult. However, graft
complications may occur following the trabeculectomy
surgery. In a retrospective study on 34 eyes in 32 patients
who underwent trabeculectomy with and without mitomy-
cin C for glaucoma after penetrating keratoplasty, two eyes
developed corneal endothelial defect after trabeculectomy,
and another two eyes experienced corneal endothelial graft
rejection. One cornea cleared with systemic corticosteroid
administration, but the other eye developed graft endothe-
lial decompensation. In this study, the final graft clarity rate
was 69.2% (18/26) in the mitomycin C (+) group and
37.5% (3/8) in the mitomycin C (−) group.41
Trabeculectomy-Related
Complications with Descemet’s
Stripping Automated  
Endothelial Keratoplasty
Descemet’s stripping automated endothelial keratoplasty
graft operation. Previous trabeculectomy operations may be
associated with a significantly increased rate of endothelial
graft dislocation compared with control eyes after Descemet’s
stripping automated endothelial keratoplasty (DSAEK). In a
retrospective, comparative analysis of an interventional
case series of 854 eyes (67 eyes with prior glaucoma surgery
and 787 controls) Jeffrey M. Goshe et al. demonstrated that
previous glaucoma surgery is associated with a significantly
increased rate of graft dislocation compared with control
eyes. In the study, postoperative graft dislocation occurred
significantly more frequently in study eyes compared with
control eyes (9% vs. 2%; p = 0.008). Among eyes in which
dislocation occurred, postoperative hypotony was present in
five study eyes (83%) and no control eyes. The authors con-
cluded that dislocation is related strongly to postoperative
hypotony in eyes with prior glaucoma surgery.42
Corneal Complications Related to
the Use of Anti-VEGF with
Trabeculectomy
Recently, anti-VEGF agents have been shown to be benefi-
cial in treating neovascular glaucoma. Their use leads to
regression of iris and angle neovascularization. In addition,
research on the wound modulatory properties of anti-VEGF
agents has revealed a dose-dependent inhibition of fibro­
blast proliferation.43 However, the use of anti-VEGF agents
can be associated with corneal, retinal and systemic side
effects. In a retrospective chart review on 850 eyes of 850
patients with neovascular eye disease and diabetic macular
edema who had received 1.25 to 2.5 mg bevacizumab dem-
onstrated that bevacizumab caused corneal epithelial
defects. Seven eyes of seven subjects developed corneal epi-
thelial defects the day after bevacizumab injection. All of
these eyes had pre-existing corneal edema. Additionally, in
the experimental arm of the same study, photorefractive
keratectomy was used to create 3 mm corneal epithelial
defects in the right eyes of 18 New Zealand rabbits which
834 SECTION 11  •  Trabeculectomy
were then randomized to three equal groups. All rabbits
received topical antibiotics, additionally those in group A
received topical bevacizumab and animals in group B were
treated with topical corticosteroids. The rate of epithelial
healing was assessed at different time points using slit-lamp
photography. In the experimental study, topical bevacizu-
mab was found to significantly hinder corneal epithelial
healing at 12 and 24 hours.44
Corneal Blood Staining
Hyphema may occur during the operation or within the
first few days afterwards. The hyphema may be associated
with increased IOP, particularly if the filtering site is
obstructed. Persistent rise in IOP in the presence of hyphema
may lead to corneal staining. In most cases of hyphema, no
treatment is necessary. The blood is often absorbed within
a brief period of time. If postoperative hyphema persists,
surgical evacuation is considered depending on the level of
IOP, the size of hyphema, the severity of optic nerve damage,
the presence of sickle cell trait or sickle cell anemia, and the
likelihood of corneal blood staining. Liquid blood can be
easily removed with anterior chamber irrigation. If a clot
has formed, it can be removed by expression with viscoelas-
tic or with a vitrectomy instrument. If necessary, the IOP
should be treated with aqueous suppressants. Injection of
a tissue plasminogen activator may be considered but there
is a risk of possible rebleeding.
Treatment with autologous blood injection into an
over-filtering bleb has also been associated with a rise in
intraocular pressure and hyphema in some patients with
postoperative hypotony. Some surgeons recommend injec-
tion of a viscoelastic into the anterior chamber prior to
blood injection into the bleb to reduce the risk of hyphema.45
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