Trabeculectomy augmentation (mitomycin C, collagen implant or both)
By
Tamer salem MD
Introduction:
Glaucoma is one of the most common and dangerous eye disorders. It is defined as
a multifactorial optic neuropathy with a characteristic acquired atrophy of the optic nerve
and loss of retinal ganglion cells and their axons; with subsequent characteristic visual
field defects. Many hemodynamic factors (e.g., ocular blood flow and ocular perfusion
pressure), have been reported to be associated with development of glaucoma (Yanagi et
al., 2011). Intraocular pressure remains the only modifiable factor that could be controlled
by different treatment modalities, such as topical eye drops, laser procedure, and surgical
intervention. Surgery is resorted when maximum tolerated medications and laser therapy
fail to control the progression of glaucomatous optic neuropathy (Huang et al., 2013).
Trabeculectomy is the most commonly performed surgical intervention to reduce
intraocular pressure for medically uncontrolled glaucoma since its introduction in 1968
(Cairns, 1968). The most common cause of surgical failure in such cases is the scarring
at the level of the conjunctiva–Tenon’s–episcleral interface, the scleral flap, its overlying
episclera, or the internal ostium (Azuara-Blanco and Katz, 1998); the introduction of the
anti-fibrotic mitomycin C (MMC) and 5-fluorouracil (5-FU) – in early 1990s - have been
used to improve surgical outcome (Rothman et al., 2000). However, antifibrotics had
significant complications (e.g., hypotony, cataract formation, avascular filtering blebs,
thinning of the conjunctiva, subsequent blebitis, and endophthalmitis) (DeBry et al., 2002;
Oyakhire and Moroi, 2004; Reibaldi et al., 2008).
These adverse effects seen with antifibrotic agent’s application have been related
to the dose and exposure times (Sanders et al., 1999; Kim et al., 1998). Different studies
have shown that MMC-related complications, especially hypotony and cataract, are more
common with increased concentration and longer exposure times (Robin et al., 1997;
Chen et al., 1990).
Different modifications of the surgical to reduce the risk of such complications had
been developed. These surgical modifications included use of glaucoma drainage
devices, deep sclerectomy, and viscocanalostomy (Gedde et al., 2007a,b; Wishart et al.,
2008; Gedde et al., 2009 ). In addition, different medications were used to reduce bleb
fibrosis; these included systemic anti-inflammatory fibrosis suppression agents (oral
prednisone, colchicine, and non-steroidal anti-inflammatory agents) for 4 to 6 weeks
during the postoperative period (Fuller et al., 2002; Vote et al., 2004).
As an alternative augmentation in trabeculectomy,- with success rate comparable to
mitomycin C, a biodegradable implants had been recently developed. It included a
combination of a polymer scaffold with a population of stem, progenitor, or precursor cells.
With subsequent development of structures, which are similar to normal tissue (Young et
al., 2005).
A porous collagen–glycosaminoglycan matrix (ologen) has been tested in animal
models and it had been reported to prevent the collapse of the subconjunctival space. A
randomized collagen deposition and microcyst formation after trabeculectomy have been
shown in the ologen group (Chen et al., 2006; Hsu et al., 2008) when compared to
negative controls. The most common advantage of the biodegradable implant is the
decrease of early postoperative scarring (Chen et al., 2006). Thus, it can maintain normal
IOP for a long time after filtering surgery, provided that, it confers a comparable reduction
in IOP. Another prospective preliminary study showed no significant difference in the
postoperative IOP after trabeculectomy in the control group and trabeculectomy with
ologen in the study group (Papaconstantinou et al., 2010).
Idea about this work:
As mitomycin C is associated with significant complications that are associated with
its dose and duration of applications; and as the studies used ologen had contradictory
results; we intended to discover the appropriate augmented method used with
trabeculectomy.
Aim of the work:
The aim of the present study is to investigate results of different augmentation
procedures used with trabeculectomy in treatment of glaucoma.
Subjects and methods:
The present study included 60 patients who presented with primary open angle
glaucoma were included. They were selected from ------- during the period from ----- to ----Inclusion criteria: adult patients with primary open angle glaucoma, age 18 or older,
had intraocular pressure above 21mmHg or progressive visual field deterioration on
maximum-tolerated medical therapy, had visual field defects, had glaucomatous optic disc
with cupping, were included in the present study.
Exclusion criteria: patients with closed-angle glaucoma, normal tension glaucoma,
posttraumatic or any form of secondary glaucoma, use of systemic or ocular medications
that might affect vision, acute or chronic disease that could confound the outcomes of the
study (eg, immunodeficiency, connective tissue disease, and diabetes), clinically
significant cataract where combined surgery was indicated, previous operated glaucoma,
and previous vitro-retinal surgery were excluded from the study.
For each patient, only one eye was operated and included in the present study.
Patients were randomly assigned to one of three equal groups: the first group included
20 subjects (eyes) who underwent Trabeculectomy with low dose mitomycin C as an
augmentation; the second group included 20 subjects (eyes) who underwent
Trabeculectomy with ologen (collagen) implant as an augmentation; and finally the third
group included 20 subjects who underwent Trabeculectomy with both low dose mitomycin
C and collagen implant as an augmentation.
Randomization was done by allocation of patient’s number to one of studied
groups, and the allocation paper was enclosed in a closed envelope, that was opened just
before surgical intervention by a nurse (not included in the study).
The preoperative data were age; gender; medical history (presence of any ocular
pathology; number of antiglaucomatous medications; applanation tonometry under
maximum-tolerated topical therapy; biomicroscopy; and computerized Humphrey visual
field testing.
Surgical technique:
All surgeries were done under local peribulbar anesthesia by the same surgeon.
The technique included grasping the superior rectus muscle with a 4-0 silk traction
suture and creating a superior fornix-based conjunctival/tenons flap with a 9-mm limbal
conjunctival incision using Westcott scissors. A rectangular 3.0x3.5mm2-wide, 300-µ thick
scleral flap was dissected at the 12-o’clock position using a bevel-up crescent knife. The
scleral flap 3.0mm side incisions were not completed up to limbus. This should encourage
greater posterior aqueous flow and a more diffuse bleb, according to the ‘Moorfields Safer
Surgery System’ (Stalmans et al., 2006).22
In MMC-augmented group, a Weck-cell sponge was cut into two to three pieces,
4mmx2mmx0.5mm, soaked with MMC at a concentration of 0.1 mg/ml and placed under
the dissected conjunctiva surrounding the scleral flap and on the scleral bed. The sponges
were left in position for 1 min in order to maintain contact with the Tenon’s capsule side of
conjunctiva. Then, the eye was irrigated with 15 ml of normal saline. An ophthalmic
viscoelastic was injected to increase the iris–cornea depth and anterior chamber was
entered at the base of scleral flap with a 3.2 precalibrated knife. Two semicircular
excisions 1.5mm in diameter were created along the same radial line, in order to obtain an
excision of corneoscleral tissue including the trabecular meshwork. A peripheral
iridectomy was then performed, followed by reinjection of viscoelastic into the anterior
chamber. The scleral flap was closed with two 10-0 nylon sutures, one at each corner,
applying minimal tension in MMC cases and with one loose stitch in OLO cases (Dhingra
and Khaw, 2009; Cillino et al., 2005).
In ologen (OLO) group, a cylindrical 2.0±0.3mm in height x 6.0±0.5mm in
diameter implant was centered on the top of scleral flap and under the conjunctiva. The
conjunctival flap was secured to the limbus with two 10-0 nylon single-stitch tensioning
sutures at the extremities of the limbal incision plus a tight 10-0 nylon running suture with
buried knots. The filtration was assessed by injecting balanced salt solution into the
paracentesis.
In combined group, after irrigation by normal saline, a 3.0x1.0mm sclerectomy was
then performed followed by a peripheral iridectomy. The scleral flap was repositioned and
closed with 1 interrupted suture of 10-0 monofilament nylon. Ologen implant (cylindrical
implant with a diameter of 7mm and a height of 4mm) was positioned on top of the scleral
flap without the use of any suture. Finally, the conjunctiva was closed with an 8-0
polyglactin vicryl suture (Dadaet al., 2013).
Postoperative treatment: topical tobramycin 0.3% five times daily for 14 days;
topical dexamethasone drops 0.1% five times daily for 7 days, three times daily for 6
weeks and twice a day for a final 1 week. If corkscrew bleb vessels were present, more
frequent topical steroid administration was allowed, according to the ‘intensified
postoperative care’ (IPC) protocol (Marquardt et al., 2004). In hypotony, 1% atropine
drops were added during the first week.
Post-discharge visits were scheduled at the end of first week, first month, 3 months,
6 months and 12 months.
Primary outcome: IOP was the primary outcome measure and the target level was
considered: <18mmHg. Complete success was defined as a target end point IOP without
antiglaucomatous drugs, while qualified success was defined as a target end point IOP
regardless of medications.
Secondary outcome measures included bleb evaluation; number of glaucoma
medications; and frequency of postoperative adjunctive procedures and complications.
Bleb evaluation was done by bleb classification score consisted of three
parameters: the avascularity, corkscrew vessels, and microcysts of the bleb (Klink et al.,
2008). The classification was done as the following: avascularity and corkscrew vessels:
0, entire bleb; 1, in two-thirds of the bleb; 2, in one-third of the bleb; 3, none. In case of
microcysts: 0, none; 1, over the scleral flap; 2, lateral and medial to the scleral flap; 3,
entire bleb.
Complications were defined as follows: encapsulated filtering bleb (Tenon’s cyst),
shallow anterior chamber, hyphema, ablation of the choroidals (e.g., choroidal effusion),
persistent leakage, hypotony (IOP <6mmHg), macular edema, corneal complications,
allergy, suprachoroidal haemorrhage, and blebitis/endophthalmitis.
Results
Table (): Preoperative data of studied cases
Age (years) (mean±SD)
Gender (male/female)
Side (right/left)
Preoperative IOP (mmHg) (mean±SD)
Number of preop. medications (mean±SD)
Duration of preop. Therapy (y) (mean±SD)
MMC
59.60±10.65
13/7
9/11
27.75±3.01
2.85±0.58
3.20±1.01
Ologen
59.50±8.55
10/10
14/6
27.45±2.23
2.70±0.57
3.30±1.03
Both
60.40±8.26
15/5
11/9
29.35±2.73
2.95±0.39
3.40±1.14
test
0.06
2.72
2.57
2.90
1.15
0.17
p
0.94
0.25
0.27
0.063
0.324
0.842
Table (2): Postoperative IOP and bleb scoring in studied cases (mmHg)
IOP at 1 week
IOP at 1 month
IOP at 3 months
IOP at 6 months
IOP at 12 months
MMC
Ologen
Both
MMC
Ologen
Both
MMC
Ologen
Both
MMC
Ologen
Both
MMC
Ologen
Both
Mean
10.40
10.45
9.90
11.25
12.30
12.95
12.65
13.40
13.30
14.35
14.15
14.30
15.35
14.70
14.55
S. D
1.35
0.99
0.91
1.58
1.65
0.99
1.63
1.27
0.80
1.59
1.13
0.80
1.53
1.12
0.88
Minimum
8.00
9.00
9.00
8.00
10.00
11.00
9.00
11.00
12.00
12.00
12.00
13.00
13.00
12.00
13.00
Maximum
13.00
12.00
12.00
14.00
15.00
15.00
16.00
16.00
15.00
18.00
16.00
16.00
18.00
16.00
16.00
Table (3): Postoperative complications and success rate in studied cases
MMC
n
%
Hyphema
2
10.0%
Shallow anterior chamber
1
5.0%
Leakage
2
10.0%
Tenon’s cyst
1
5.0%
Complete
17
85.0%
Success
Qualified
3
15.0%
NB: no cases reported hypotony, or revision surgery
n
1
2
4
0
12
8
Ologen
%
5.0%
10.0%
20.0%
0.0%
60.0%
40.0%
Both
n
0
2
2
0
17
3
%
0.0%
10.0%
10.0%
0.0%
85.0%
15.0%
Statistics
X2
p
2.10
0.34
5
8.3%
1.15
0.56
2.03
0.36
4.65
0.09
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