This document discusses ideal properties of glues for wound closure and different types of glues used in ophthalmic surgery. It focuses on fibrin glue and cyanoacrylate glues, comparing their mechanisms of action, preparation methods, application techniques, advantages, and disadvantages. Fibrin glue mimics the body's natural coagulation cascade and is absorbable, while cyanoacrylate glue forms a solid impermeable mass that can cause inflammation. Both glues have important applications in ophthalmic procedures when used appropriately.
2. ideal glue properties
• 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
3. TYPES
• synthetic (commonest is n-butyl-2-cyanoacrylate).
• biological (fibrin glue).
in addition:
• Gelatin and thrombin products
• Albumin and glutaraldehyde products
• Polyethylene glycol polymers
4. CYANOACRYLATE
• Cyanoacrylate-based glues have traditionally been the most widely
used glues for ophthalmic surgery.
• Cyanoacrylates require minimal hydration to polymerise and set. They
can only be used externally because they induce inflammation.
• The tensile strength of the bonding is one of the highest of all glues.
The major draw back of cyanoacrylate glue is that they form a solid,
impermeable mass in situ .
5. • This persists as a foreign body causing inflammatory reactions like
giant papillary conjunctivitis and corneal neovascularization.
• They are also impermeable to fluids and metabolites. Though these
disadvantages preclude its intraocular use, they are not very
significant if the glue is applied superficially
6. FIBRIN GLUE
• Fibrin glue is a blood-derived product that is absorbable, relatively
easy to use, and can be kept at room temperature or in a refrigerator
• Fibrin glue is a biological tissue adhesive which imitates the final
stages of the coagulation cascade when a solution of human
fibrinogen is activated by thrombin (the two components of fibrin
glue).
• Fibrin glue includes a fibrinogen component and a thrombin
component, both prepared by processing plasma. It can be prepared
at a blood transfusion center or from patients own blood or obtained
as a commercially available preparation.
7. • When it is derived from individual volunteer donations, it may have a
low concentration of fibrinogen.
• The commercially availableproducts are produced from pools of
plasma, usually contain high yields of fibrinogen and,
consequently, produce firm coagulums.
• Unlike cyanoacrylate glue, fibrin glue forms a smooth seal along the
entire length of the wound edge and thereby provides greater
postoperative comfort to the patient with fewer complications.
8. MECHANISM OF ACTION
• Fibrin glue mimics the final coagulation cascade resulting in its adhesive
capability.
prothrombin
factor X fibrinogen
thrombin
fibrin
factor XIII ca+ (stabilizes the clot by promoting polymerization n
crosslinking of fibrin chains to form long strands.)
9. 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.
10. METHODS OF PREPERATION
• The autologous source avoids any possible risk of viral transmission.
• Homologous fibrin glue is prepared from donors screened like other blood
products, followed by inactivation of viruses by solvent / detergent treatment.
• The plasma is centrifuged to produce:precipitate containing fibrinogen
supernatant containing thrombin.
• The precipitate is resuspended in a small volume of the supernatant and used as
the fibrinogen component.
• The supernatant is further treated by clotting to convert residual fibrinogen to
fibrin followed by its filtration to isolate the fibrin.
• The resulting serum is used as the thrombin component.
11. The various methods of preparation are:
• Fibrinogen: Modified Hartman's Procedure
• Thrombin: Armand J Quick method
• Fibrinogen rich concentrate
• Preparation during emergency need
12. Commercial available fibrin glue
1. Large Blue Bottle: Sealer protein concentrate (Human), Freeze dried, vapour treated, 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 mg (microgram)
2. Small Blue Bottle: Aprotinin solution, bovine 3000 KIU /ml
3. White Bottle: Thrombin 4 (bovine), freeze dried reconstituted contains 4IU/ml
4. Large Black Bottle: Thrombin 500 (bovine), freeze dried reconstituted contains 500 IU/ml
5. Small Black Bottle: Calcium chloride solution, 40mmol/L 1+2 (Fibrin component)
13. • 3+5 (Thrombin component)- Used for slow release
4+5 (Thrombin component)- Used for rapid release
• Before use, the syringes containing two components of fibrin glue,
namely, Thrombin (Black) and Fibrinogen (Blue) are taken out from
the deep freeze and thawed to room temperature.
14. TECHINQUES OF APPLICATION
• 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
• the more dilute thrombin solution, thrombin 4 ,results in a clot in
about 60 seconds after glue application to the surgical field.
15. • For 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.
16. ADVANTAGE
• Fibrin glue reduces the total surgical time because time required to
place sutures is saved. The use of glue has been found to lower the
risk of post-operative wound infection, contrary to conventional
suturing.
• Mixtures of fibrin glue and antibiotics are being used for local delivery
of antimicrobial activity.It is well tolerated, non-toxic to the tissue.
• 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.
17. DISADVANTAGES
• The major drawback to its use is the risk of transmitted disease from
pooled and single-donor blood donors.
• The safest preparation is by using the patient's own blood to prepare
fibrin glue.
• 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. • Refractive surgery
treating epithelial in growth
as a temporary basement membrane
in flap tear
• Glaucoma surgery
conjunctival closure
management of post operative leaking bleb
GDD surgery
• Lens surgery
• Vitreoretinal sugery
• Lid n adnexal surgery
lid surgery
lacrimal surgery
20. conclusion
• It reduces surgical time
• Adequate bond strength, good sealent, safe, minimal allergic or toxic
reactions and minimizes bleeding
• Easy to undo
• Disappears eventually
• Can plug perforations
• Excess amount can be trimmed
• Does not produce inflammation
25. Antibiotic therapy
Combination therapy
• A combination therapy consists of a cephalosporin, which acts against
the gram-positive cocci and some of the gram-negative rods and an
aminoglycoside which acts against the gram negative organisms.
• Alternatively one of newer generation fluoroquinolonesmay also be
combined with fortified cefazolin.
• Combined fortified 5% cefazolin sodium and 1.3% tobramycin
sulphate are given in hourly dosage for the initial 48 hours.
26. Monotherapy
• Ciprofloxacin 0.3%, ofloxacin 0.3 %,Gatifloxacin 0.3% or moxifloxacin
0.5 % can be given as monotherapy and is effective against most
corneal pathogens.Additionally they are also effective against most
strains of aminoglycoside resistant Pseudomonas, methicillin resistant
Staphylococcus.
28. Specific drugs
• For Nocardia keratitis trimethoprim (16 mg/ml) and sulfametoxazole (
80 mg/ml) is the treatment of choice.Alternatively,
sulfonamides,tetracyclines,erythromycin or amikacin may be used.
• In cases of acid fast-stained positive corneal scrapings topical
amikacin 10 to 20 mg/ml one drop every hour is indicated.systemic
amikacin used in cases of corneal perforation or scleral involvement.
• More recently, the fluroquinolones have found to be effective against
mycobacteria and can be used as a first line of treatment combination
29. Systemic therapy
• Systemic antibiotics are started along with the topical antibiotics in
cases of severe keratitis with scleral melting, impending perforation,
frank perforations.
• which have a propensity for intraocular spread and also when the
infection occurs in children due to H. influenza and P. aeruginosa.
30. Signs of healing
• The signs and symptoms decrease and visual acuity continues to
improve.
• The stromal infiltrates consolidate
• anterior chamber reaction decreases.
• Epithelialization is complete
• necrotic stroma is replaced by scar tissue laid down by fibroblasts.
• Vascularisation occurs and following complete healing the vessels
regress completely but sometimes leave “ghost vessels” which are
visible through indirect illumination.
32. Signs of progression
• increase in the size of the infiltrate,
• epithelial defect,
• height of hypopyon,
• Corneal thinning
• eventually perforation
33. Surgical therapy
• Tissue adhesives:Cyanoacrylate glue to treat small perforations (less
than 2mm), progressive stromal keratolysis and thinned descemetoceles.
• The tissue adhesive is known to have anti-bacterial activity. However, since
it is toxic to the corneal endothelium , it should be used with caution.
• It restores the integrity of the cornea, till the antimicrobial therapy can
reduce the ulceration size.
• The edges and the bed of the site of the perforation is dried completely
before application of the glue following which a therapeutic bandage
contact lens is placed.
34. • PATCH GRAFTS:Patch grafts of upto 5 mm diameter may be used to
debulk the cornea and to remove the clinically visible margin of the infected
area. It is preferable to encompass 1 mm of the normal cornea in the
trephinated area.
35. • THERAPEUTIC KERATOPLASTY:If there are large areas of perforation
or necrotic tissue,a therapeutic keratoplasty is indicated.
• Pre-operatively,maximal antibiotic therapy to eradicate infection and
to reduce inflammation is recommended.
• It is preferable to encompass 1mm of the normal cornea in the
trephinated area.
• Further, the corneal button obtained should be sent for
microbiological culture and histopathological examination.
• Post operatively, systemic antibiotic therapy should also be given
along with the topical antimicrobial agents and topical
corticosteroids.
39. • natamycin 5% suspension is the initial drug of choice for fungal
keratitis.It should be given hourly during the day and two hourly
during night time.
• In addition to the anti-fungal drugs a broad-spectrum antibiotic such
as a fluroquinolone may be given to prevent secondary bacterial
infection.
• Additionally, cycloplegics such as homatropine eye drops may be
given 3 times a day to relieve the component of iridocyclitis.
40. • anti-glaucoma medications in cases where the intraocular
pressure is high on digital tonometry.
• Once the infiltrate started resolving, the frequency of topical
natamycin is reduced to 2-hourly until the completion of
resolution.
• The natamycin should be continued for 2 weeks after the
resolution of infection in all cases.
41. • If worsening of the keratitis is observed on topical natamycin, topical
amphotericin B 0.15% with or without fluconazole 2 percent may be
added as a second agent.
• In cases of proven Candida sp., amphotericin B 0.15 percent or
fluconazole 0.3 percent is the first drugs of choice
42. • The efficacy of Econazole 1% against filamentous fungi has been
found to be equivalent to natamycin 5%.
• Clotrimazole is available in 1%topical drops and ointment form and
has been used in the treatment of fungal keratitis.
• The imidazoles (ketoconazole and miconazole) are used systemically
for the treatment of keratomycosis because of their relatively reduced
systemic toxicity.
• Fluconazole is a fungistatic bitriazole which is used topically and
systemically in the treatment of Candida and Aspergillus keratitis.
• It does not show encouraging results against Fusarium species.
43. • Voriconazole, is derived from Fluconazole and exhibits a wider
spectrum of activity against Candida, Aspergillus and Fusarium
• It exerts its effect from inhibition of cytochrome P450-dependant 14
alpha sterol demethylase, an enzyme involved in the ergosterol
biosynthetic pathway
• The minimal inhibitory concentration of voriconazole(0.5 μg/ml) is
less as compared to other imidazoles.
44. Response to treatment
• diminution of pain,
• decrease in size of infiltrate,
• disappearance of satellite lesions,
• rounding out of the feathery margins of the ulcer and hyperplastic
masses, or fibrous sheets.
46. Duration of treatment
• The duration of the treatment for topical treatment has not been
firmly established clinically or experimentally.
• Problems that can rise from prolonged treatment are due to toxicity.
• The inflammatory response from this toxicity can be confused with
persistent infection.
• If toxicity is suspected and if adequate treatment has been given for
at least 4 to 6 weeks, treatment should be discontinued and the
patient carefully observed for evidence of recurrence.
47. Drug interactions
• Synergistic drugs include a combination of amphotericin B and
flucytosine, (for Candida keratitis)
• A combination of natamycin and ketoconazole (for Aspergillus
keratitis)
48. Systemic therapy
• Treatment with a systemic anti-fungal agent is recommended in cases of very large
ulcers, severe deep keratitis, scleritis and endophthalmitis.
• Systemic antifungals also may be used as prophylactic treatment after penetrating
keratoplasty for fungal keratitis.
• The drugs, which have been used systemically,include:
ketoconazole (oral),
miconazole (intravenous)
itraconazole (orally 200 mg/day)
fluconazole (orally 200 mg/day).
• More recently oval voriconazole 200 mg bd has shown good results in recalcitrant fungal
keratitis.
• The most frequently used oral anti-fungal is ketoconazole, which is given in the dose of
600 mg per day.
• It is mandatory to assess liver function tests every 2 weeks after starting ketoconazole.
• Systemic therapy is given for a period of 6 to 8 weeks
49. Intracameral therapy
• Intracameral amphotericin B may be a useful modality in the
treatment of severe keratomycosis not responding to topical
natamycin.
• It ensures adequate drug delivery into the anterior chamber and may
be especially useful to avoid surgical intervention in the acute stage of
the disease.
• Patients with deep keratomycosis unresponsive to conventional
medical treatment are candidates for intracameral injections of 5 μg
to 7.5 μg amphotericinB in 0.1 mL 5 percent dextrose.
51. Intrastromal therapy
• intracorneal Amphotericin B injection in 5-7.5 μg dosage, given in the
vicinity of the stromal site of fungal growth.
• This would raise the local concentration of the antifungal agent
enough to be effective in the eradication of the deep corneal
infection.
• This approach proves effective, with total elimination of the infection
• The intrastromal injection can be repeated after a period of 48 to 72
hours
52.
53. Surgical therapy
Debridment:Daily debridement with a spatula or blade is the
simplest form of surgical intervention and is usually performed at the
slit lamp under topical anesthesia.
Debridement is performed every 24 to 48 hours and works by
debulking organisms and necrotic material and by enhancing the
penetration of the topical antifungal.
54. Therapeutic Keratoplasty
• Most retrospective series indicate that keratoplasty was performed
within 4 weeks of presentation,
• Primarily because of medical treatment failures;in some cases it may
be required because of recurrence of infection.
• If the infectious process is allowed to progress until it involves the
limbus or sclera, unfavorable outcomes secondary to
scleritis,endophthalmitis, and recurrence are more common.
• Therapeutic keratoplasty should be performed in cases of impending
perforations, frank perforations > 2 mm or if there is no response to
therapy
55. • The size of the trephination should leave a 1 to 1.5 mm clear zone of
clinically uninvolved cornea to reduce the possibility of residual fungal
organisms peripheral to the trephination.
• Interrupted sutures with slightly longer bites should be used to avoid
cheese wiring of the suture if the edge of the recipient becomes
involved with a persistent organism.
• The specimens removed should be submitted to both the
microbiology and pathology laboratories for culture and fixed section
examination.
56. • Histopathologic examination of corneal buttons can reveal the
presence of fungal elements in 75 %Patients
• It has been shown that 59 %of corneas infected by fungi are still
culture-positive at the time of keratoplasty, with 90 percent of eyes
exhibiting hyphal elements on pathologic examination
• Fungal hyphae usually lie parallel to the corneal surface and lamellae.
• A vertical or perpendicular arrangement of fungal hyphae in the
corneal stroma has been associated with increased virulence and in
patients on topical corticosteroid therapy.
57. • After penetrating keratoplasty, topical antifungal agents should be
continued to prevent recurrence of infection.
• If the pathology laboratory reports that no organisms were seen at
the edge of the corneal specimen, anti-fungals could be stopped after
2 weeks and the patient followed carefully for recurrences.
• Although the main goal of penetrating keratoplasty in fungal keratitis
is to eliminate the infecting organism.
• A secondary goal is the maintenance of a clear corneal transplant for
optical reasons.
58. • Even if graft failure or rejection occurs, the patient can undergo a
second optical keratoplasty once the rejection is controlled.