2. OUTLINE
• Introduction
• History of fibrin glue in ophthalmology
• Properties of an idea tissue adhesives
• Different types of Fibrin & its production
• Mechanism of action of fibrin
• The technique for application
• Advantages and disadvantages
• Use in ophthalmology
• Conclusion
• References
3. INTRODUCTION
• A surgical suturing ,aka a stitch or stitches, is the act of holding
body tissues together or apposing wound edges with the use of
suture.
• Suturing is time consuming and due to nonavailability of an ideal
suture which should be easy to handle, non-allergenic, and should not
promote infection.
• Search for alternatives which is tissue adhesives were sorted and are
being increasingly used.
• Fibrin is a biodegradable biological adhesive, It induced minimal
inflammation
4. INTRODUCTION
• It is the only agent presently approved as a hemostat, sealant, and
adhesive by the Food and Drug Administration (FDA).
• The two basic categories of tissue adhesives are
• synthetic (commonest is n-butyl-2-cyanoacrylate)
• biological (fibrin glue)
• In addition to these two tissue adhesives, newer adhesives available for
surgeons are: •
• Gelatin and thrombin products •
• Albumin and glutaraldehyde products •
• Polyethylene glycol polymers
• The product is now supplied as patches in addition to the original liquid
formulations
5. HISTORY OF FIBRIN SEALANT
• Fibrin was first introduced in 1909, it was not until 1944 that Tidrick et al.
used fibrin for skin graft fixation.
• Fibrin glue was introduced to ophthalmology early forties to fixate
penetrating corneal grafts in rabbits.
• As early as 1986 the glue was used in conjunctival surgery utilizing
pericardium
• A number of authors have tried its efficacy with favorable outcome.
• In strabismus surgery Spierer et al. in 1997 carried out an experimental
study using fibrin glue in strabismus surgery for conjunctival closure.
• Jiang et al. in 2008 evaluated the efficacy and safety of fibrin glue in
conjunctival autograft fixation in primary pterygium compared with that
of suturing
6. HISTORY OF FIBRIN SEALANT
• An experimental study was carried out by Erbil et al. in 1991 where fibrin
glue was used for conjunctival wound closure in place of classical sutures.
• Histopathological study revealed better results with fibrin sealant than
those with sutures.
• Tisseel a commercially available fibrin biosealant has been used in
Europe for more than 25 years in over 9.5 million surgical procedures
• Currently, its use has gained popularity for both conjunctival closure and
transplant.
7. Properties of an idea tissue adhesives
• Must allow sufficient working time before inducing firm adhesion.
• Must have adequate tensile strength to maintain wound integrity.
• Must be biocompatible
• Should be clear enough to permit vision.
• Should be permeable to fluids and metabolites to prevent necrosis.
• Must not induce inflammation.
• Must disappear eventually to permit healing at the interface.
• Should not carry the risk of transferring an infectious agent.
• Accessible and affordable
8. WHAT IS FIBRIN AND HOW TO GET
• Fibrin glue is a blood-derived product
that contains following component
• Sealant protein containing human
fibrinogen, plasminogen, fibronectin,
and factor XIII reconstituted in a bovine
aprotinin solution
• Sealant solution composing of human
thrombin reconstituted in a calcium
chloride solution.
• Available as a
• Commercially(as homologous ) eg Tisseel
and Reliseal
• Autologous produced locally from patients
blood during the surgery
9. Methods of preparation(autologous)
• 10 ml of patient's blood is collected in sterile
0.9% sodium citrate containing vacutainers
• This is first centrifuged at 3000 rpm for 10 min.
• This vacutainer now had a top layer of platelet-
poor plasma, a middle layer of platelet-rich
plasma, and the bottom fraction of red blood
cells (RBCs).
• The platelet-poor and platelet-rich plasma were
aspirated into a sterile syringe and kept in
another test tube without anticoagulant . RBC
fraction was discarded.
• Protamine sulfate 10 mg/ml was added to
platelet-rich and platelet-poor plasma for
precipitation of maximum quantity of fibrinogen
and centrifuged for another centrifuged at 1000
rpm for 5 min.
• The centrifuged tube contained a top layer of
serum with thrombin (autologous) and the
bottom part of fibrinogen precipitate
• The top serum was discarded, retaining 0.5 ml
of it in the test tube to dilute fibrinogen
precipitate.
• Add 0.025 mmol/l of calcium chloride
10. Commercial fibrin glue
• The commercially available fibrin glue are
produced from pools of plasma from donors
blood which are screened like blood products
, followed by inactivation of viruses by solvent
detergent treatment.
• They are freeze dried and vapour treated.
• It usually contain high yields of fibrinogen
and, consequently, produce firm coagulums.
• Products are maintained in cold chain from
the time after preparation till use.
11. • Large Blue Bottle: Sealer (human) protein
concentrate containing
• Clottable protein - 75 to 115mg
• Fibrinogen - 70 to 110mg
• Plasma fibronectin - 2 to 9 mg
• Factor XIII - 10 to 50 IU
• Plasminogen - 40 to 120 µg
• Small Blue Bottle: Aprotinin solution, bovine
3000 KIU /ml
• White Bottle: Thrombin 4 (bovine), contains
4IU/ml
• Large Black Bottle: Thrombin 500 (bovine),
contains 500 IU/ml
• Small Black Bottle: Calcium chloride solution,
40mmol/L.
12. Fibrin glue Preparation(Homologous)
• The components of fibrin glue are taken out
from the deep freeze and thawed to room
temperature.
• The fibrinolysis inhibitor (Aprotinin) is added to
protein concentrate and stirred, also calcium
chloride is injected into the Thrombin vial
(Thrombin 500 or 4, depending upon whether
an early or a delayed clot is required).
• The two vials are warmed for several minutes in
a patented fibrinotherm device.
• These solutions are filled into two separate
disposable syringes
13. Fibrin glue Preparation(homologous)
• The filled disposable syringes are placed
side by side into the duploject injector
• A mixer nosecone, topped by a blunt
applicator needle, is attached to the 2-
syringe nozzle to facilitate mixing of the two
syringe components.
• When the common plunger is depressed,
the fibrin sealer solution and the thrombin
solution are combined in the nosecone, in
equal volumes, to form the resulting fibrin
sealant that is directly applied to the
designated tissues
14. Mechanism of action of fibrin glue
• The principle is based on wound healing following
injury where the inciting inflammation allows
formation of thrombus (clot) through a series of
events in the coagulation cascade.
• Fibrin glue mimics this coagulation cascade resulting
in its adhesive capability
• Fibrin glue bypass the initial extrinsic and intrinsic
coagulation cascade but replicate the physiological
final common pathway of coagulation cascade.
• Thrombin activate fibrinogen to fibrin monomer,
Factor XIII (present in the fibrinogen component of
the glue) cross links and stabilizes the clot’s fibrin
monomers while aprotinin inhibits fibrinolytic
enzymes, consequently resulting in a stable clot.
• There is subsequent proliferation of fibroblasts and
formation of granulation tissue within hours of clot
polymerization.
• Clot organization is complete two weeks after
application.
• The resultant fibrin clot degrades physiologically
15.
16. The technique for application
SIMULTANEOUSLY
• The two components of fibrin glue are
simultaneous loaded into two syringes
with tips forming a common port
(Duploject syringe).
• When injected, the two components
meet in equal volumes at the point of
delivery.
• The thrombin converts the fibrinogen
to fibrin by enzymatic action at a rate
determined by the concentration of
thrombin.
• The more concentrated thrombin
solution , thrombin 500, produces a
fibrin clot in about 10 seconds and the
more dilute thrombin solution,
thrombin 4 ,results in a clot in about 60
seconds after glue application to the
surgical field.
SEQUENTIAL APPLICATION
• Thrombin is first applied on to the area of
interest, followed by a thin layer of
fibrinogen.
• In a minute or two, coagulation starts and
by two or three minutes, polymerization
is complete.
• Alternatively, when apposition is required
between opposing surfaces, thrombin
solution may be applied to one and
fibrinogen to the other surface.
17. The technique for application
• In all of these cases, prior to application of the glue, the surgical field
must be dried meticulously.
• After application, the tissue is pressed gently over the glue for 3
minutes for firm adhesion.
• At the end of the procedure, pad and bandage is applied after
instillation of antibiotic drops.
• Use of broad spectrum antibiotics
• Use of aqueous suppressant if applicable,
• Preservative free artificial tears
• Use of protective shield , bandage contact lens and glasses always
18. Advantages
• Reduces total surgical time
• Lower the risk of post-operative wound
infection.
• Local delivery of antimicrobial activity
• It is well tolerated, non-toxic to the
tissue
• Low incidence of allergic reaction
• Its absorbable, relatively easy to use,
and can be kept at room temperature or
in a refrigerator
• The smooth seal along the entire length
of the wound edge results in a higher
tensile strength, with the bond being
resistant to greater shearing stress.
• Use as adjunct to control bleeding in
selected surgical patients.
Disadvantages
• Risk of virus transmission, though most but
not all viruses can be inactivated by solvent
/ detergent treatment.
• It is expensive and autologous donation
requires at least 24 hours for processing.
• Has limited shelf life, not always
available on demand, takes time to
prepare
• The resultant product often has variable
concentrations thereby resulting in an
unpredictable performance.
• Moreover, tensile strength of fibrin glue has
not been adequately determined and
precludes quantification, being dependant
on various extraneous factors also.
19. Disavantages
• Chances of allergic reaction to
bovine protein though rare.
• Difficulty in procuring the materials
for preparation, multiple
components involved (fibrinogen,
thrombin, afibrinolytics, and
calcium chloride)
• Temperature-sensitive preparation
procedures
• Difficult, and time-consuming
chairside preparation methods
20. Use of fibrin
• Fibrin sealant remains useful :
• Hemostat(as intraoperative and postoperative)
• sealant
• Adhesive.
21. Lid and adnexal surgery
• a) Lid surgery
• for fixing the free autologous skin transplants to cover defects
• advantageous
• Allows early fibrovascular ingrowth into the graft
•
• In lower eyelid trichiasis,
• used for fixation of free autologous conjunctival transplants from the upper fornix
after separation of the lashes from the posterior lamella with a lid split technique.
• In blepharoplasty
• Advantage:
• 52% reduction in bruising and 83% decrease in hematoma formation
• Few stitches and better cosmesis
22. Lacrimal surgery
• Indications
• Fibrin glue is used for reconstructing lacerated canaliculi
• Canaliculocystotomy
• Canaliculodacryocystorhinostomy
• Endonasal endoscopic dacryocystorhinostomy.
• Microanastomosis between canaliculi and lacrimal sac
• For attaching lacrimal and nasal mucosal flaps.
• Dacryocystectomy to distend and delineate the lacrimal sac and fistula to aid
complete dissection
23. Fibrin Glue Application Enhances Surgical Success Rate in Endonasal Endoscopic
Dacryocystorhinostomy With Lacrimal Sac Preservation
The surgical success rate was significantly higher in the
fibrin glue anastomosis group (95.5%) than in the non
fibrin glue group (84.8%; P = .041)
24. Periocular cystic lesions
• Injection of fibrin glue mixed with
either indocyanine green or trypan
blue into periocular cystic lesions
will delineate the wall thus
simplified the surgery and
prevented complications such as
injury to surrounding vital
structures and reduced the
likelihood of recurrence.
• ICG may be superior to trypan blue
but a comparative controlled study
is needed to assess the difference.
25. Conjunctival tissue
• Pterygium:
• conjunctival autografts for wound closure
• amniotic membrane graft fixation
• Disadvantage:
• recurrent eye rubbing can cause graft
dehiscence
• In case of refractory conjunctivochalasis
• amniotic membrane transplantation can
achieve a complete smooth conjunctival
surface
26. Conjunctival
• In glaucoma surgery
• Conjunctival wound closure in
glaucoma surgery has been
described by O'Sullivan et al. in
1996.
• Management of post
trabeculectomy
hypotony(postoperative bleb leak)
• In glaucoma drainage device:
• Fibrin glue help reduce peribulbar
filtration and preventing immediate
post operative hypotony after GDD
surgery.
Post trabeculectomy bleb leak
27. Conjunctival
• In strabismus surgery
• use of fibrin glue for conjunctival
wound closure in place of classical
sutures
(A) Commercial fibrin glue (Greenplast®). (B)
Application of Greenplast® on scleral corners
along the free edges of the conjunctival flap. (C)
Using two forceps, opposing edges of the
conjunctiva are pressed and attached to each
other. (D) Conjunctival wound closed using fibrin.
28. Stabismus surgery
• Fibrin glue can be use to fix
recessed horizontal extraocular
muscle
• Advantage
• Fast, safe and effective with
postoperative results similar to
SFR.
• it eliminating the complication of
retinal perforation that can occur
with SFR especially in thin sclera
• Avoid under- or overcorrection that
can occur with traditional hang-
back recession.
29. CORNEAL
Indications
• Corneal ulcer perforation < 2mm
• Cornea melt/ descemetocele
• Cornea ulcer impending perforation
• Corneal graft in corneal perforation in
trauma
• Leaking corneal wounds post
phacoemulsification
• Perforated hydrops
• In refractory and perforated corneal ulcers ,
amniotic membrane transplantation
Intracameral fibrin glue in corneal
perforation
30. • Whitening of the fibrin glue indicated
a stable perforation closure 10 min
after application.
• Absorption of human fibrin glue
occurs within 2 weeks
• Advantage:
• Reduce risk of corneal transplant
rejection
31. • Liu et al. used fibrin glue to fix a
polymethyl methacrylate ring to
an amniotic membrane patch on
the ocular surface as a
therapeutic contact lens
32. KERATOPLASTY
• Lamellar keratoplasty:
• To fixate the lamellar corneal graft
• Deep anterior lamellar
keratoplasty
• Both recipient bed and donor
buttons are of same size and
thickness
• Top Hat” keratoplasty
• Fibrin glue was mechanically more
stable than suturing
(a) Clinical photograph of left eye showing the
scarred and vascularized graft due to a
bacterial infection. (b) Photograph of the
additional sutures placed in the inferonasal
quadrant (arrow) after repeating the
penetrating keratoplasty. (c) Cobalt-blue light
picture after the injection of fibrin glue in the
anterior chamber at the G–H junction, showing
the arrest of leakage (asterisk).
33. Limbal cell transplantation(vacuum-dried amniotic
membrane and fibrin glue)
• Fibrin glue effectively and safely fix
the donor limbal lenticule on the bed
of the recipient in cases of limbal
deficiency.
• Advantages:
• Eliminate suture related problems
• Tissue apposition due to the thin
lenticule
• suture related inflammation,
vascularization
• Patient discomfort to the exposed
sutures on the ocular surface
34. Epikeratophakia
• Using biological adhesive,
Rostron et al. reduced the
operating time to 50% when
glue was used instead of
sutures.
• Bond strength was 140 gm/cm.
similar with cyanoacrylate glue
36. Refractive surgery
• Treating epithelial ingrowth
• In recalcitrant cases of epithelial
ingrowth fibrin glue forms a
mechanical barrier and prevents
the epithelial cells from growing
underneath the flap, at least until
the flap is healed.
• Also use as bandage contact lens
or as an ocular surface bandage
but has poor optical surface.
37. REFRACTIVE SURGERY
• In flap tear or flap dislocation:
especially post trauma, which
some epithelial defect, fibrin
glue adheres better to the
denuded surface on or around
the flap and prevents epithelial
ingrowth.
• Used as a temporary basement
membrane in photorefractive
keratectomy to reduce corneal
haze
38. LENS SURGERY
• Seal small cataract wound incision to
prevent post operative astigmatism.
• To close both anterior and posterior
capsular perforation
• 1`1 To fix the haptics of IOL to the
scleral tissue in place of sutures.
• Two partial-thickness limbal-based
scleral flaps are made 180 degrees
apart diagonally, and the haptics of the
PC IOL are externalized to place them
beneath the flaps.
• This simple method of PC IOL
implantation requires no
specially designed haptics.
• It provides good flap closure
and IOL centration and stability
without suture-related
• Glued endocapsular hemi-
ring segment for fibrin
glue-assisted sutureless
transscleral fixation of
the capsular bag in
subluxated cataracts and
intraocular lenses
39. Vitreoretinal surgery
INDICATIONS
• Conjunctival wound closure
following retinal detachment
surgery.
• Conjunctival peritomy for
buckle implantation
• In case of persistence conjunctival
wound leak
• 20- 23 guage leaking sclerotomies
• Macular hole surgery
• In an optic pit,
• In subretinal space in a giant
retinal tear(tear (glue-assisted
retinopexy for rhegmatogenous
retinal detachment (GuARD).
• To cover exposed RPE
40. use of fibrin glue to close a
leaking sclerotomy using a
20-gauge cannula
Fixation of conjunctiva after
applying fibrin glue in its
borders for 60 s
fibrin glue in
conjunctival
peritomy fixation
after a successful
retinal detachment
surgery.
Application of fibrin glue
during a retinopexy
procedure using a 20-gauge
cannula and a 3 ml syringe
41. VITREORETINAL SURGERY
ADVANTAGE
• Early visual rehabilitation,
• Lower incidences of
complications as seen with
tamponading agents,
including cataract formation,
elevated intraocular pressure,
• it eliminates the postoperative
face-down position
requirements
DISADVANTAGE
• Epiretinal proliferation.
• Can migrate subfoveally
leading to subnormal visual
recovery.
• Excess contraction of glue
leading to proliferative
vitreoretinopathy (PVR)
42. CONCLUSION
• Fibrin glue is a blood product which can be gotten from patient
making it readily available.
• Fibrin glue is a sealant , reducing surgical time as compared to
suturing.
• It is safe with minimal allergic or toxic reactions and incite mild
inflammation rarely.
• It’s a hemostas, thus minimizes intraoperative and post
operative blood loss.
• Its is an option I will like us to consider.
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