Pterygium, Tissue Glue, and the Future
of Wound Closure
Sadeer B. Hannush
14
Key Points
Surgical Indications
• Pterygium and other surface surgery with con- junctival or amniotic membrane graft ing Instrumentation
• Fibrin sealant Surgical Technique
• Excision of pterygium
• Harvesting of conjunctival graft
• Securing graft (or amniotic membrane) in po- sition with fi brin sealant
Complications
• Rapid setting of fi brin sealant
• Conjunctival graft retraction
14.1
Introduction
Pterygium represents fi broelastic degeneration of the conjunctiva with encroachment onto the cornea, caus- ing chronic infl ammation and frequently interfering with vision. It usually occurs nasally but can occur elsewhere. It is more common in hot, dry, windy envi- ronments with increased exposure to ultraviolet radia- tion [1]. Some have speculated damage to limbal epi- thelial stem cells as an etiology, though this has not been proven. A hereditary component has been con- sidered as an etiology as well [2].
When chronic infl ammation is present, signifi cant corneal astigmatism is induced, or vision is threatened, surgical removal of the pterygium is indicated. More than a hundred techniques have been described over the past several centuries because of concern over re- currence.
Cornea specialists favor one of two approaches for surgical removal, simple excision with primary closure aft er controlled application of mitomycin C intraop- eratively [3] or excision followed by free conjunctival autograft or amniotic membrane transplantation (with or without mitomycin C application). Th e conjunctival or amniotic membrane graft s are traditionally secured in position with 10-0 monofi lament nylon or 7-0 to
10-0 absorbable Vicryl™ suture [3–6]. Suturing adds signifi cantly to operative time and contributes to post- operative infl ammation and discomfort.
14.2
Surgical Indications
Th e historical indications for pterygium surgery have included (1) visual disturbance either through en- croachment over the pupillary aperture or by signifi - cantly aff ecting corneal toricity and inducing corneal astigmatism, (2) documented enlargement over time in the direction of the center of the cornea, (3) chronic symptomatic infl ammation, (4) motility disturbance limiting abduction (more common with recurrent pte- rygium), and (5) cosmesis.
Recurrence is the major complication of pterygium surgery, therefore various techniques have been advo- cated, including the use of β-radiation, 5-fl uorouracil, thiotepa, and mitomycin C. Th e technique favored by many cornea specialists includes intraoperative appli- cation of mitomycin C, as well as conjunctival or am- niotic membrane transplantation aft er simple excision.
Recent concerns over potential long-term eff ects of mitomycin use have increased the popularity of con- junctival or amniotic membrane transplantation.
14.3
Instrumentation and Equipment
Th e use of an operating microscope is all but manda- tory in pterygium surgery, in addition to standard mi- crosurgical instruments and fi brin sealant or tissue glue ( Tisseel). Standard microsurgical instruments re- quired include calipers, 0.12-mm forceps, smooth conjunctival forceps, Wescott scissors, cautery, mi- croneedle driver (when sutures are used), nylon or Vicryl™ suture material, no. 64 beaver blade, diamond dusted burr, and amniotic membrane if a conjunctival autograft is not used.
Historically, a free conjunctival autograft or amni- otic membrane has been secured in place with either 10-0 monofi lament nylon or with 7-0 to 10-0 absorb-
able Vicryl™ sutures. Suture placement may add sig- nifi cantly to the operative time. Sutures are usually as- sociated with signifi cant postoperative discomfort and infl ammation. Nylon sutures have to be removed, whereas Vicryl™, although absorbable, may last several weeks and may be associated with increased postop- erative infl ammation.
At this time there are limited choices for tissue clo- sure with a fi brin sealant or tissue adhesive. Tisseel VH fi brin sealant (Baxter, Vienna, Austria) is a two-compo- nent tissue adhesive, which mimics natural fi brin for- mation by utilizing the last step of the blood coagulation cascade, where fi brinogen is converted by thrombin to form a solid-phase fi brin clot. Fibrin sealants have been used over the past two decades in general surgery for repair of hepatic and splenic ruptures as well as for bow- el anastomoses, in orthopedic and gynecologic surgery, as well as in dermatologic surgery for skin graft s in burn patients [7, 8]. In ophthalmology, fi brin sealants have found applications in oculoplastic and cosmetic surgery, for conjunctival closure in strabismus surgery [9–11], for repair of bleb leaks aft er glaucoma fi ltering surgery [12–16], and for repair of conjunctival lacerations and corneal perforations [17–20]. Recent reports have advo- cated the use of fi brin sealants for lamellar keratoplasty [21, 22] and for management of recurrent epithelial in- growth aft er LASIK [23]. A recent application of fi brin sealants is the fi xation of conjunctival autograft s at the time of pterygium surgery [24–28]. However, at the time of this writing ocular use of Tisseel fi brin sealant remains an off label use as Food and Drug Administra- tion (FDA) approval has not been obtained for this indi- cation.
Th e source of the thrombin and fi brinogen in Tis- seel VH fi brin sealant is pooled human sera. Donors are tested, and retested aft er a three-month interval, for viral infections including hepatitis B and C, HIV, and human parvovirus. Th e source of the aprotinin in Tisseel is bovine, from closed herds in areas of the world with no history of bovine spongiform encepha- litis (BSE or mad cow disease). Vapor heating adds an- other measure of safety to the product. In more than 10 million uses of Tisseel, there have been no reports of infection with hepatitis, HIV, or BSE, and only two reports (more with other fi brin glues [29]) of trans- mission of human parvovirus B19 (HPV B19) before 1999, when polymerase chain reaction testing was in- stituted for HPV.
14.4
Surgical Technique
Under topical, subconjunctival, or peribulbar anesthe- sia, the pterygium is excised with the individual sur- geon’s preferred technique (Fig. 14.1). Removal of a
limited amount of adjacent conjunctiva and Tenon’s capsule is recommended. Depending on the severity of the pterygium, excision of surrounding subconjuncti- val Tenon’s capsule may be indicated if excessive scar- ring is present. Limited cautery is applied as necessary.
A diamond-dusted burr on a high-speed drill or a no.
64 beaver blade is used to smooth the peripheral cor- nea and limbus [27]. Th e excised specimen is submit- ted for pathologic examination to confi rm the diagno- sis. Placement of the specimen fl at on fi lter paper allows the pathologist the ability to examine the lesion in the clinical orientation, without excessive curling or folding of the tissue. An appropriately sized conjuncti- val graft (equal or slightly larger than the conjunctival defect), with or without adjacent limbal epithelium (surgeon’s preference) is harvested in the usual man- ner from the superotemporal quadrant (if the pterygi- um is nasal) and slid nasally, keeping the limbal edge facing the limbus, to cover the exposed scleral bed cre- ated by the pterygium excision. If tissue adhesive is not available, the conjunctival graft is secured into posi- tion with sutures. Th e limbal aspect of the conjunctival graft is secured with two interrupted 10-0 nylon su- tures at the limbus. Each interrupted suture includes episcleral tissue and is tied with a slipknot. Th e ends are cut short, and the knots are buried in the cornea.
Th ese sutures are removed 2 to 6 weeks postoperative- ly. Th e remaining conjunctival graft is secured with 9-0 Vicryl™ sutures. Interrupted sutures may be used with inclusion of episcleral tissue to stabilize the graft , or a running suture of the same material may be used. Ei- ther way the corners of the graft need to be anchored to the episcleral tissue to prevent dislocation or slip- page of the graft during the healing process. Th e Vic- ryl™ suture is secured with a surgeon’s knot and the ends are cut short. Th e knots are not buried, as they quickly soft en and cause little irritation.
Tissue adhesive allows a more rapid closure of the conjunctival graft without the issue of discomfort and infl ammation that may result from sutures. In this technique, the surgical assistant prepares the two com- ponents of the Tisseel VH fi brin sealant using the manufacturer’s instructions while the surgeon removes the pterygium. Th e product may be delivered to the ocular surface in either of two ways to form the fi brin clot. Th e fi rst technique involves application through the Duploject syringe supplied in the Tisseel VH kit:
aft er combining the two components in the Y-connec- tor, ten drops are wasted before injecting one drop un- der the conjunctival graft . Th e graft is then rapidly po- sitioned by smoothing out (pasting) the graft over the scleral bed with a smooth instrument. Th e coagulum (fi brin clot) starts forming in 5 to 7 s, achieves 70% of its fi nal tensile strength in 10 min, and full strength in 2 h. Th e second technique is a more controlled joining of the two components and may be achieved by fl ip-
ping the conjunctival autograft epithelial side down onto the cornea adjacent to its fi nal resting place ([25];
Fig. 14.2). One drop of the thrombin solution is placed on the scleral bed and one drop of the protein solution on the underside of the conjunctival graft (now facing up) (Fig. 14.3) before the graft is fl ipped over and glued into position (Fig. 14.4). Th e graft is smoothed into position. Any excess product that comes out from un- der the graft may be trimmed aft er it clots, with a pair of 0.12-mm forceps and Wescott scissors. Th e product does not adhere to epithelialized conjunctival or cor- neal surfaces. Aft er 2 to 3 minof observation, the spec- ulum is removed, and a spontaneous or forced-blink test is performed (depending on the type of anesthetic) to confi rm that the graft is securely in place. An antibi- otic–steroid ointment is applied over the ocular sur- face, and the case terminated. Postoperative antibiotics and steroids are used per the surgeon’s preference.
Th e above procedure using tissue adhesive may be completed in signifi cantly less time than if sutures are utilized. Moreover, postoperative discomfort is decid- edly less than with any type of suture. Of course, suture removal is obviated. Th e eyes appear quieter aft er Tis- seel VH fi brin sealant is used than with sutures (Fig.
14.5). Th is may be explained by the absence of the ir- ritating sutures themselves, the potential antiinfl am- matory properties of Tisseel, or the prevention of pe- ripheral fi broblast migration under the graft . Th e rate of recurrence of pterygium with this technique appears equal or less [26] than with suture placement.
For those surgeons who prefer to use amniotic membrane ( AmnioGraft ™ or AmbioDry™) instead of conjunctiva for the graft to cover the area exposed af- ter the pterygium is removed, the exact same technique may be utilized. Care must be taken to keep the base- ment membrane side of the amnion up. Also, amnion may be a little more diffi cult to manipulate than con- junctiva. Should the dried version of amnion (Ambio- Dry™) be used, we suggest gluing it in position before hydration.
Th e same technique may be adopted for more ex- tensive ocular surface surgery with amniotic mem- brane transplantation.
14.5
Complications and Future Challenges
As with any surgical procedure, there is a learning curve involved with the use of Tisseel VH fi brin seal- ant for pterygium surgery. Complications arise from using too much product (rarely, too little) and not squeegeeing excess product out from under the graft , which may then be trimmed with scissors once the co- agulum forms. If the product is not distributed evenly
under the graft , the graft may have an edematous ap- Fig. 14.4 Th e conjunctival autograft is fl ipped over and pasted onto the scleral bed
Fig. 14.1 Pterygium is excised using surgeon’s technique of choice. Conjunctival autograft is harvested with or without limbal epithelium
Fig. 14.2 Th e conjunctival autograft is prepared and fl ipped over, epithelial side down on the cornea in preparation for transfer nasally
Fig. 14.3 Th e conjunctival autograft is positioned nasally epithelial side down onto the cornea, limbal side facing the limbus. A drop of thrombin solution (A) is placed on the scleral bed, and a drop of fi brinogen/protein (B) on the auto- graft
pearance in the early postoperative period. Any parts of the underlying sclera not receiving Tisseel will lead to poor adherence and retraction of the graft . Th e sur- geon should pay close attention to the edges of the graft as he or she lays it fl at on the scleral bed avoiding rolling-in of the edges or incomplete coverage of the defect.
Some surgeons have complained that the rapid for- mation of the fi brin clot does not allow adequate time for controlled placement of the graft in the desired manner at the desired location. Th is may be easily ad-
dressed by diluting the thrombin component (500 IU/
ml, original concentration aft er constitution, intended for rapid clot formation in other types of surgery) with stock CaCl2 in a 1:100 concentration, resulting in a thrombin concentration of 5 IU/ml [30]. At this con- centration, the time required for fi brin clot formation may be 30 to 60 s, allowing ample time of proper ma- nipulation of the graft by the surgeon. Some have even advocated doing away altogether with the thrombin component and allowing the patient’s own blood to form the clot with only one Tisseel component (fi brin- ogen/protein).
Of note, Tisseel VH fi brin sealant is used elsewhere in the body at sites subjected to higher shearing forces than the ocular surface, where the only forces are those of the blinking lid or inadvertent eye rubbing. Future challenges include the ability to determine whether Tisseel VH fi brin sealant or other tissue glues (chemi- cal, biodendrimers [31, 32], etc.) may be able to replace suture for other types of ocular wound closure, espe- cially those subjected to higher shearing forces.
As exciting as this technology is for decreasing sur- gical time and postoperative discomfort, a few things are worth mentioning. First, despite the impeccable track record of Tisseel VH fi brin sealant, anytime the product source is pooled human sera and bovine pro- tein, the possibility exists, at least in principle, for transmission of viral [27] and prion disease. Secondly, the cost of a 1-ml vial of Tisseel is three to four times that of one pack of nylon or Vicryl™ suture. However, one vial of Tisseel may be used for four to fi ve cases on the same day if this can be arranged, since only a few drops are needed for each case. Th is makes the use of Tisseel less expensive than suture, even before taking into consideration the amount of savings incurred in reduced operating room time.
In conclusion, Tisseel VH fi brin sealant may be an alternative to suture for securing a conjunctival or am- niotic membrane graft during pterygium surgery. It shortens surgical time, may lead to faster surface reha- bilitation, and is more comfortable for the patient.
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