17553768, 2013, 5, Downloaded from https://onlinelibrary.wiley.com/doi/10.1111/j.1755-3768.2012.02436.x by CAPES, Wiley Online Library on [04/11/2022].

See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License
Acta Ophthalmologica 2013

Use of a fibrin adhesive for

conjunctival closure in
trabeculectomy
José M. Martinez-de-la-Casa, Omar Rayward, Federico
Saenz-Frances, Carmen Mendez, Enrique Santos Bueso and
Julián Garcia-Feijoo
Ophthalmology Department, Clinico San Carlos Hospital, Ophthalmology
Department of Medicine School, Complutense University of Madrid, Health
Investigative Institute of Clinico San Carlos Hospital (IdISSC), Madrid, Spain

ABSTRACT. reduced (Heijl et al. 2002; Leske et al.

Purpose: To assess the safety and efficacy of a fibrin tissue adhesive (Tissucol 2003; Folgar et al. 2010). Among the
Duo) used to close the conjunctiva in trabeculectomy. different surgical techniques, trabecu-
Methods: A nonrandomized prospective study including 57 patients with lectomy with or without antimetabo-
chronic simple glaucoma who underwent trabeculectomy surgery. All the trabe- lites is the most widely used procedure
culectomies were conducted by the same surgeon using the same surgical tech- to surgically treat glaucoma. Despite
nique with the exception that conjunctival closure was achieved by either numerous variants of this surgical
technique, the basic procedure is simi-
running Nylon 10 ⁄ 0 suture (n = 29) or using the fibrin glue (n = 28). Preop-
lar and consists of opening the con-
erative and postoperative data were obtained on intraocular pressure (IOP),
junctiva to create a superficial scleral
number of hypotensive medications used, self-reported discomfort and compli- flap, resection of part of the trabecu-
cations arising during and after surgery. lar meshwork and closure of the
Results: No differences were detected between the two patient groups regard- superficial scleral flap and conjunctiva
ing the intraocular pressure reduction achieved during follow-up. In the first (Papaconstantinou et al. 2010).
2 weeks of follow-up, reported discomfort assessed using a visual analogue The most frequent cause of trabecu-
scale was significantly lower in the Tissucol Duo group. Two patients in the lectomy failure is episcleral fibrosis
Tissucol Duo group suffered conjunctival dehiscence and suturing was and thickening of the conjunctiva
required at 24 hours postsurgery. Remaining complications were similar in the directly overlying the filtering zone
two groups. (Cvenkel et al. 2010). This process of
Conclusion: The use of Tissucol Duo seems to be a safe and efficient option scarring and tissue remodelling contin-
for conjunctival closure in trabeculectomy that simplifies the surgical proce- ues indefinitely following surgery and
dure and reduces patient discomfort in the immediate postoperative period. leads to an increase in the failure rate
as the duration of patient follow-up
Key words: conjunctiva – tisseel – Tissucol Duo – trabeculectomy.
increases (Van Buskirk 1996). The tis-
sue adhesives currently available may
be classified into the two types: syn-
Acta Ophthalmol. 2013: 91: 425–428 thetic (cyanoacrylate) and biological
ª 2012 The Authors
Acta Ophthalmologica ª 2012 Acta Ophthalmologica Scandinavica Foundation (fibrin) (Forseth et al. 1992).
Synthetic adhesives have been tradi-
doi: 10.1111/j.1755-3768.2012.02436.x tionally the most commonly used in
ophthalmology practice. However,
main risk factor for the appearance they can only be used externally
and progression of chronic simple because they cause inflammation.
Introduction glaucoma (Sommer et al. 1991; Weih Thus, after the use of a synthetic
In patients with glaucoma, the surgi- et al. 2001) and several studies have adhesive, it compacts down to form a
cal procedure of trabeculectomy shown that by reducing IOP, whether solid mass that may produce a foreign
achieves a reduction in intraocular pharmacologically or surgically, the body sensation and induce inflam-
pressure (IOP). An elevated IOP is the risk of disease progression is also matory reactions such as papillary

425

Acta Ophthalmologica 2013
conjunctivitis or corneal neovascular-
ization (Carlson & Wilhelmus 1987).
Biological glues based on fibrin
have been used in ophthalmology for
over 20 years, with reported applica-
tions in procedures of conjunctival,
corneal, cataract (Buschmann 1987),
glaucoma, vitreo-retinal (Batman
et al. 2008), refractive (Anderson &
Hardten 2003) and strabismus sur-
gery. Fibrin glues form a soft film
over the applied zone and are gener-
ally better tolerated and related to a
lower incidence of complications than
synthetic glues (Sharma et al. 2003).
This study was designed to compare
the safety and efficacy of the use of a
fibrin glue (Tissucol Duo, Baxter,
Deerfield, IL, USA) for conjunctival
closure during trabeculectomy surgery
to the more conventional closure
method by means of Nylon 10 ⁄ 0
suture. The main outcome measures
recorded were IOP, number of hypo-
tensive medications, postoperative dis-
comfort measured using a visual
analogue scale, surgery time and intra-
operative and postoperative complica-
tions.
Materials and Methods
A prospective nonrandomized study
was conducted on 57 patients with
primary open angle glaucoma man-
aged at our Glaucoma Department
who had been programmed to
undergo trabeculectomy surgery for
IOP control. The patients were
required to not have undergone prior
eye surgery. Candidates for other
types of glaucoma surgery or those
planned to undergo combined cataract
and glaucoma surgery were not
included in this study. Further exclu-
sion criteria were a second trabeculec-
tomy, the presence of another
ophthalmologic pathology or an
inability to understand the explana-
tion of the procedures given to obtain
consent.
Informed consent was obtained
from each patient according to the
tenets of the Declaration of Helsinki.
The study protocol was approved by
our institution’s review board.
Between 7 and 30 days before sur-
gery, all patients were subjected to an
ophthalmologic examination in which
other ocular or poorly-controlled sys-
temic diseases that could interfere
with the surgery outcome were ruled
426
out and each patient’s baseline IOP
was established. Between this preoper-
ative visit and surgery, the patients
were instructed to continue using the
eye drops they were prescribed for
controlling their glaucoma.
The same surgical technique was
conducted in all patients and all the
surgeries were carried out by the same
surgeon (JMC). The only difference in
the surgical technique was the method
used for conjunctival closure. Thus,
patients were divided in two consecu-
tive groups: in group I (n = 29), con-
junctival closure was achieved by
Nylon 10 ⁄ 0 running suture and in
group II (n = 28) using Tissucol
Duo. Fibrin glues such as Tissucol
Duo have biological components
that reproduce the final stages of the
blood coagulation cascade. The com-
ponents fibrinogen and thrombin are
obtained by processing human blood
plasma (Panda et al. 2009).
The surgical technique consisted of
creating a fornix-based conjunctival
flap. Antimetabolites were not used in
any of the operations. Nylon 9 ⁄ 0
suture was used to close the scleral
flap, and conjunctival closure was
achieved in each group as described
previously. When the fibrin sealant
was used, it was applied in a sequen-
tial fashion to prevent fibrin leakage
to the scleral flap. If the fibrin sealant
reaches the scleral flap, this could
become occluded preventing an ade-
quate flow of the aqueous humour to
the subconjuctival space. After both
edges of the conjunctival peritomy
were connected, the fibrinogen was
initially applied and immediately after
this, the thrombin was placed on top
of the former. Moderate pressure was
applied to the edges of the conjuncti-
val peritomy for approximately
30 seconds using a pair of forceps to
achieve satisfactory closure. In the
group I patients, the conjunctival
suture was removed 2 weeks after sur-
gery.
Follow-up visits were planned for
24-hours, 1 week, 2 weeks and 1, 3
and 6 months postsurgery. If compli-
cations were reported in the 24-hr fol-
low-up visit, revision surgery was
performed on this day.
All tests were performed at
9:00 h ± 1 h to reduce diurnal varia-
tion. In each examination, IOP was
determined with an applanation
tonometer. A 0-to-10 visual analogue
17553768, 2013, 5, Downloaded from https://onlinelibrary.wiley.com/doi/10.1111/j.1755-3768.2012.02436.x by CAPES, Wiley Online Library on [04/11/2022]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License
scale (VAS; UPSA Institute) (Bijur
et al. 2001) was used for the patients
to objectively determine the degree of
pain suffered during the first postop-
erative weeks. Patients were asked to
slide a marker along one side of a
scale, which shows a bar that gets
progressively wider such that the
observer, blind to the type of conjunc-
tival closure used, can quantify the
pain according to the numerical scale
on the underside.
Data were statistically treated using
the spss 18.0 program for Windows
(SPSS Inc., Chicago, IL, USA). The
Kolmogorov–Smirnov test was used
to check for the normal distribution
of quantitative data. Data were com-
pared between the two groups using
the Student’s t-test and Pearson’s lin-
ear correlation test. The level of sig-
nificance was set at p < 0.05.
Results
Mean patient ages at the time of sur-
gery were 65 ± 9.5 years in group I
and 67.1 ± 7.5 years in group II. The
mean IOPs recorded at baseline and
1, 3 and 6 months postsurgery were
20.6 ± 6.1, 16.8 ± 6.8, 15.4 ± 4.2
and 15.1 ± 5.2 mmHg, respectively,
in group I (Nylon 10 ⁄ 0 suture) and
22.7 ± 5.9, 15.5 ± 5.6, 15.1 ± 3.7
and 15.3 ± 4.3 mmHg in group II
(fibrin glue) (Fig. 1); with no signifi-
cant differences (p = 0.357) observed
between the groups. The numbers of
hypotensive topical medications used
in each group were 2.4 ± 0.7,
0.2 ± 0.5, 0.3 ± 0.7 and 0.4 ± 0.8
(preoperative and 1, 3 and 6 months
postoperative) in group I and
2.2 ± 0.5, 0.1 ± 0.3, 0.2 ± 0.5 and
0.3 ± 0.5 in group II (Fig. 2); with
no significant differences between
groups (p = 0.952).
Mean duration of surgery was
37.3 ± 4.4 min in group I and
34.0 ± 4.2 min in group II; the differ-
ence being significant (p = 0.006).
Mean visual analogue scale scores of
patient discomfort were 4.7 ± 1.4,
2.6 ± 0.9 and 0.1 ± 0.3 in group I
and 3.5 ± 1.3, 1.5 ± 0.6 and
0.2 ± 0.4 in group II at 1 week
(p = 0.002), 2 weeks (p < 0.001) and
1 month (p = 0.425), respectively,
(Fig. 3).
In two patients in the fibrin sealant
group, conjunctival dehiscence was
detected in the 24-hr follow-up visit.
 17553768, 2013, 5, Downloaded from https://onlinelibrary.wiley.com/doi/10.1111/j.1755-3768.2012.02436.x by CAPES, Wiley Online Library on [04/11/2022]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License
Acta Ophthalmologica 2013

25 treatment is reserved for cases in

Nylon group Tissucol Group
which neither medical nor laser treat-
20
ments are sufficient to control IOP
(Parrish et al. 2009).
15
Trabeculectomy is perhaps the fil-
10
tering technique most used for the
surgical treatment of glaucoma.
5 Removing a portion of trabecular
meshwork reduces resistance to aque-
0 ous humour outflow thus reducing
Basal 1 month 3 months 6 months
post-op post-op post-op IOP. Although the mechanisms
whereby aqueous humour drains are
Fig. 1. Mean intraocular pressures (mmHg) recorded during the study (p = 0.357). not yet fully understood, its diffusion
through the walls of the conjunctival
filtration bleb is considered critical
3
Nylon group Tissucol group
(D’Ermo et al. 1979; Levene 1984a,b).
2.5 The failure of a trabeculectomy is
mostly associated with excessive fibro-
2
sis in the subconjunctival space
1.5
(Hitchings & Grierson 1983) because
this impairs adequate aqueous drain-
1 age. Hence, the use of methods or
procedures to minimize subconjuncti-
0.5
val inflammation and scar tissue for-
0 mation in response to trabeculectomy
Basal 1 month 3 months 6 months surgery could help control IOP in
post-op post-op post-op
these patients (Carpineto et al. 2011).
Fig. 2. Mean number of hypotensive medications used by the patients (p = 0.952). The use of biological tissue adhe-
sives was described for the first time
in glaucoma surgery when a leaking
5 bleb was treated with fibrin glue in
Nylon group Tissucol group
4.5 1990. (Kajiwara 1990) Since then,
4 many authors have reported on the
3.5 use of tissue adhesives for different
3
glaucoma surgery manoeuvers such as
2.5
conjunctival and scleral closure in tra-
beculectomy (O’Sullivan et al. 1996;
2
Bahar et al. 2006), or in the different
1.5
steps of valve placement surgery to
1
replace the sutures used to close the
0.5
conjunctiva and fix the pericardial
0
1 week post-op 2 weeks post-op 1 month post-op patch or control leakage (Kahook &
Noecker 2006).
Fig. 3. Mean self-reported scores of ocular discomfort obtained using the visual analogue scale One of the theoretical advantages
at 1 week (p = 0.002), 2 weeks (p < 0.001) and 1 month (p = 0.425). of the use of a tissue adhesive over
suture in conjunctival closure is the
reduced conjunctival inflammation
These patients were surgically treated haemorrhage that cleared up without induced (Kahook & Noecker 2006)
with Nylon 10 ⁄ 0 suture as soon as surgical intervention. and the consequent possible reduction
dehiscence was detected and these in subconjunctival fibrosis that occurs
patients were excluded from the study. at the level of the filtering bleb. Thus,
No patient in the suture group
Discussion the use of Tissucol Duo in conjuncti-
showed conjunctival dehiscence. Fur- Glaucoma filtering surgery aims to val closure could prove to be efficient
ther complications were mild and achieve a reduction in IOP by creating and safe to improve the control of
transient and comparable in both a route for aqueous humour to drain IOP following a trabeculectomy. In
groups. Mild hyphema was the most from the anterior chamber to the sub- the present study, we did not observe
frequent complication (affecting 4 eyes conjunctival space. The final objective improved IOP control nor the need
in group I and 3 in group II). A shal- of surgery is to achieve a stable IOP for fewer hypotensive medications
low anterior chamber was observed in that will prevent the advance of the during the 6 months of follow-up. In
3 and 4 patients in groups I and II, patient’s visual field defects (Spaeth the longer term, we should be able to
respectively. One patient in the suture 1985) and thus maintain his or her determine whether the diminished
group suffered a mild suprachoroidal quality of life. Currently, surgical conjunctival fibrosis induced by the

427

Acta Ophthalmologica 2013
biological fibrin sealant modifies the
surgical effect.
According to our findings, the use
of a biological tissue sealant to
achieve conjunctival closure does not
lead to significant complications
during surgery and diminishes the
discomfort in the immediate postoper-
ative related to the use of sutures
(until their removal at 7 to 14 days
postsurgery). The technique is also
able to slightly shorten the surgery
time, though this has scarce clinical
implications.
The use of a biological tissue adhe-
sive is not, however, devoid of pitfalls.
In effect, two of our patients suffered
conjunctival dehiscence in the immedi-
ate postoperative. In both cases, this
occurred in the same surgery session
such that it could be attributed to a
defective lot of adhesive or its modifi-
cation during thawing. A further
drawback of the technique is the sur-
gery cost increase. The cost of each
2-ml vial of Tissucol Duo used here
for each conjunctival closure is
roughly 250 USD. However, given
that 0.5 ml of sealant would be suffi-
cient for this particular purpose, an
appropriately reduced-volume presen-
tation of the product would cut the
cost of using Tissucol Duo by 75%
(to around 63 USD). Despite this pos-
sibility, its cost is still significantly
greater than the cost of a Nylon 10 ⁄ 0
suture (around 15 USD).
Tissucol Duo should not be used in
patients who are allergic to bovine-ori-
gin proteins because this could trigger
anaphylactic reactions to aprotinin
(Shirai et al. 2005). A further theoreti-
cal disadvantage of the use of biologi-
cal tissue adhesives is the risk
of transmission of nonencapsulated
viruses such as HIV or hepatitis C, or
of prions. Notwithstanding, to the best
of our knowledge, there are no
described cases of viral or prion infec-
tion associated with the use of a fibrin
glue.
In conclusion, our findings indicate
that the use of a fibrin adhesive for
conjunctival closure in trabeculectomy
is a safe and effective alternative to
the use of sutures. Tissucol Duo
shortens the time of surgery and
improves patient discomfort during
the first weeks after surgery with no
significant effects on the pressure-low-
ering efficiency of treatment. In our
patient series, two cases of conjuncti-
428
val dehiscence were produced such
that this possibility should be kept in
mind when using a tissue adhesive to
close the conjunctiva in glaucoma sur-
gery.
Acknowledgments
Instituto de Salud Carlos III, ‘Red temáti-
ca de Investigación Cooperativa. Proyecto
RD07 ⁄ 0062: Patologı́a ocular del envejec-
imiento, calidad visual y calidad de vida.’
Grupo de Investigación de la Universidad
Complutense de Madrid 920415-GR58 ⁄ 08.
References
Anderson N.J. & Hardten D.R. (2003): Fibrin glue
for the prevention of epithelial ingrowth after
laser in situ keratomileusis. J Cataract Refract
Surg 29: 1425–1429.
Bahar I., Lusky M., Gaton D., Robinson A., Avi-
sar R. & Weinberger D. (2006): The use of fibrin
adhesive in trabeculectomy: a pilot study. Br J
Ophthalmol 90: 1430.
Batman C., Ozdamar Y., Aslan O., Sonmez K.,
Mutevelli S. & Zilelioglu G. (2008): Tissue glue
in sutureless vitreoretinal surgery for the treat-
ment of wound leakage. Ophthalmic Surg Lasers
Imaging 39: 100–106.
Bijur P.E., Silver W. & Gallagher E.J. (2001): Reli-
ability of the visual analog scale for measurement
of acute pain. Acad Emerg Med 8: 1153–1157.
Buschmann W. (1987): Microsurgical treatment of
lens capsule perforations – Part II: clinical appli-
cations and results. Ophthalmic Surg 18: 276–
282.
Carlson A.N. & Wilhelmus K.R. (1987): Giant pap-
illary conjunctivitis associated with cyanoacrylate
glue. Am J Ophthalmol 104: 437–438.
Carpineto P., Agnifili L., Nubile M., Fasanella V.,
Doronzo E., Mastropasqua A. & Ciancaglini M.
(2011): Conjunctival and corneal findings in
bleb-associated endophthalmitis: an in vivo con-
focal microscopy study. Acta Ophthalmol 89:
388–395.
Cvenkel B., Kopitar A.N. & Ihan A. (2010): Inflam-
matory molecules in aqueous humour and on
ocular surface and glaucoma surgery outcome.
Mediators Inflamm 2010: 939602.
D’Ermo F., Bonomi L. & Doro D. (1979): A criti-
cal analysis of the long-term results of trabeculec-
tomy. Am J Ophthalmol 88: 829–835.
Folgar F.A., de Moraes C.G., Prata T.S., Teng
C.C., Tello C., Ritch R. & Liebmann J.M.
(2010): Glaucoma surgery decreases the rates of
localized and global visual field progression. Am
J Ophthalmol 149: 258.e2–264.e2.
Forseth M., O’Grady K. & Toriumi D.M. (1992):
The current status of cyanoacrylate and fibrin tis-
sue adhesives. J Long Term Eff Med Implants 2:
221–233.
Heijl A., Leske M.C., Bengtsson B., Hyman L. &
Hussein M. (2002): Reduction of intraocular
pressure and glaucoma progression: results from
the Early Manifest Glaucoma Trial. Arch Oph-
thalmol 120: 1268–1279.
Hitchings R.A. & Grierson I. (1983): Clinico patho-
logical correlation in eyes with failed fistulizing
surgery. Trans Ophthalmol Soc UK 103: 84–88.
Kahook M.Y. & Noecker R.J. (2006): Fibrin glue-
assisted glaucoma drainage device surgery. Br J
Ophthalmol 90: 1486–1489.
17553768, 2013, 5, Downloaded from https://onlinelibrary.wiley.com/doi/10.1111/j.1755-3768.2012.02436.x by CAPES, Wiley Online Library on [04/11/2022]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License
Kajiwara K. (1990): Repair of a leaking bleb with
fibrin glue. Am J Ophthalmol 109: 599–601.
Leske M.C., Heijl A., Hussein M., Bengtsson B.,
Hyman L. & Komaroff E. (2003): Factors for
glaucoma progression and the effect of treatment:
the early manifest glaucoma trial. Arch Ophthal-
mol 121: 48–56.
Levene R.Z. (1984a): Glaucoma filtering surgery
factors that determine pressure control. Trans
Am Ophthalmol Soc 82: 282–301.
Levene R.Z. (1984b): Glaucoma filtering surgery:
factors that determine pressure control. Ophthal-
mic Surg 15: 475–483.
O’Sullivan F., Dalton R. & Rostron C.K. (1996):
Fibrin glue: an alternative method of wound clo-
sure in glaucoma surgery.
J Glaucoma 5: 367–370.
Panda A., Kumar S., Kumar A., Bansal R. & Bhar-
tiya S. (2009): Fibrin glue in ophthalmology.
Indian J Ophthalmol 57: 371–379.
Papaconstantinou D., Georgalas I., Karmiris E.,
Diagourtas A., Koutsandrea C., Ladas I., Apos-
tolopoulos M. & Georgopoulos G. (2010): Trabe-
culectomy with OloGen versus trabeculectomy
for the treatment of glaucoma: a pilot study.
Acta Ophthalmol 88: 80–85.
Parrish R.K. 2nd, Feuer W.J., Schiffman J.C., Lich-
ter P.R. & Musch D.C. (2009): Five-year follow-
up optic disc findings of the Collaborative Initial
Glaucoma Treatment Study. Am J Ophthalmol
147: 717–724.
Sharma A., Kaur R., Kumar S., Gupta P., Pandav
S., Patnaik B. & Gupta A. (2003): Fibrin glue
versus N-butyl-2-cyanoacrylate in corneal perfo-
rations. Ophthalmology 110: 291–298.
Shirai T., Shimota H., Chida K., Sano S., Takeu-
chi Y. & Yasueda H. (2005): Anaphylaxis to
aprotinin in fibrin sealant. Intern Med 44:
1088–1089.
Sommer A., Tielsch J.M., Katz J., Quigley H.A.,
Gottsch J.D., Javitt J. & Singh K. (1991): Rela-
tionship between intraocular pressure and pri-
mary open angle glaucoma among white and
black Americans. The Baltimore Eye Survey.
Arch Ophthalmol 109: 1090–1095.
Spaeth G.L. (1985): The effect of change in intraoc-
ular pressure on the natural history of glaucoma:
lowering intraocular pressure in glaucoma can
result in improvement of visual fields. Trans
Ophthalmol Soc UK 104(Pt 3): 256–264.
Van Buskirk E.M. (1996): Five-year follow-up of
the Fluorouracil Filtering Surgery Study. Am J
Ophthalmol 122: 751–752.
Weih L.M., Nanjan M., McCarty C.A. & Taylor
H.R. (2001): Prevalence and predictors of open-
angle glaucoma: results from the visual impair-
ment project. Ophthalmology 108: 1966–1972.
Received on November 6th, 2011.
Accepted March 1st, 2012.
Correspondence:
Jose M Martı́nez-de-la-Casa, PhD
Department of Ophthalmology
Hospital Clı́nico San Carlos
Madrid and Instituto de Investigaciones Oft-
almológicas Ramon Castroviejo
Universidad Complutense
28040 Madrid
Spain
Tel: + 34913303977
Fax: + 34913303975
Email: martinezcasa@ya.com