Filtering Surgery in the Management of Glaucoma
Mahmoud A. Khaimi, MD and Marcos Reyes, MD
Glaucoma filtration surgery is performed to provide an alternative route for aqueous humor efflux from the anterior chamber and past the diseased trabecular meshwork to a space external to the eye. Aqueous then collects underneath the conjunctiva and Tenon’s capsule, an area known as the bleb, to be carried away by blood vessels and transudation past the bleb wall. The desired result is to decrease the intraocular pressure (IOP) to a lower level that would slow down or halt the progression of axonal loss that is characteristic of glaucomatous optic neuropathy.
Embarking on incisional surgery for the treatment of glaucoma is a major decision made between patient and physician (Table 60-1). Typically, this becomes a viable management alternative after medical and laser treatment have failed to reduce IOP to the desired level. Indications for advancing therapy are progressive glaucomatous optic nerve with characteristic cupping of the nerve and/or visual field loss or uncontrolled elevation of IOP that has a high likelihood of producing optic nerve damage. Many techniques and procedural variations have been developed to bypass the diseased trabecular meshwork. In the past, unguarded or full-thickness surgery was primarily used.1 However, the incidence of postoperative hypotony, with its associated complications, was extremely high. Since that time, our understanding of surgical approaches has evolved, and our techniques have improved to include partial-thickness surgery with the use of adjunctive antimetabolites. Today, guarded filtration surgery, also commonly referred to as partial-thickness trabeculectomy, is the primary operation performed for the surgical management of glaucoma. What follows is a discussion of the various concerns that must be taken into account when deciding on and performing filtration surgery.
PREOPERATIVE ASSESSMENT
Many factors contribute to the final outcome of filtration surgery. In some cases, the risk factors for failure can be modified or reduced by taking specific courses of action before and during filtration surgery.
With the exception of highly myopic patients, younger patients are at increased risk for filtration failure. The younger the patient, the greater the risk.2 Other risk factors for filtration failure include diabetes,2 higher preoperative IOP,2 Black ancestry,3 neovascularization,3 uveitis,3 and prior failed surgery.3 A concerted effort to reduce pre- and postoperative scarring and inflammation is imperative. Intra- and/or postoperative antimetabolite therapy increases the success rate of all filtration surgery and especially in those with the above risks.4–7 Older patients with memory difficulties or physical handicaps require additional attention and education. Discussing the perioperative process with family or other support people or occasionally consulting with social services may be necessary. It is crucial to establish that the patient will be able to care for him- or herself or be cared for before surgery is undertaken. The patient and appropriate family members must understand that the postoperative care is just as important as the surgery itself and that, without adequate care, the surgery can ultimately end in failure and perhaps potentially lead to adverse postoperative issues such as prolonged uveitis, posterior synechiae, and cystoid macular edema.
Other considerations relate to the preoperative ocular status (Table 60-2). Hyperopic eyes, particularly those that are very small (axial length < 21 mm) frequently have an axially shallow anterior chamber. There may be a history of chronic angle closure. These eyes are prone to postoperative shallow or flat chambers or, more rarely, malignant glaucoma. Such complications can be reduced by using tighter scleral flap closure to guard against postoperative hypotony and by minimizing intraoperative hypotony by use of anterior chamber maintainers or viscoelastics. Preoperatively, every eye should be evaluated for conjunctival mobility, especially with a history of prior surgery. Special care should be taken in the vicinity of scleral incisions or where vitreous may be present near the planned sclerectomy site. A scleral flap may be difficult to create and at risk for amputation in eyes that have undergone previous surgery. Proper preoperative planning for placement of the scleral flap will allow the careful surgeon to mitigate these issues.
Progressive visual field loss or optic nerve cupping despite maximally tolerated medical and/or laser therapy |
Uncontrolled IOP that could lead to progressive visual field loss or optic nerve cupping |
Inability to achieve IOP (usually low teens) in patients with visual field loss approaching fixation (unable to follow for progression) |
TOPICAL AND SYSTEMIC MEDICATIONS
Factors that increase pre- and postoperative inflammation should be reduced. One of these factors is the use of preoperative glaucoma medications. Generally speaking, topical and oral glaucoma medications may be continued until the day of surgery. Topical medications, such as beta-blockers, may be stopped 24 to 48 hours before filtration surgery. In patients taking timolol, it has been shown that aqueous humor production begins to increase to baseline levels only after 3 to 4 days.8 Though currently this may not be performed routinely, historically, surgeons found it to be advantageous to try to promote aqueous humor production in patients undergoing filtration surgery to reduce the incidence of postoperative hypotony.
Preoperative steroids may be useful in those patients with uveitic glaucoma where inflammation poses an increased risk for surgical failure. This approach needs to be individualized for each patient. The use of topical steroids such as prednisolone acetate 1% every 2 hours 24 to 48 hours before filtration surgery may be useful. Some surgeons find a short course of perioperative oral corticosteroids to be of benefit in those patients with a history of severe uveitis or in those with active inflammation needing urgent surgery. Preoperative systemic steroids can produce a wide variety of serious adverse effects and should only be used in selected cases and after consultation with an internist or uveitis specialist.
Hyperopic Eyes |
More prone to shallow or flat anterior chambers postoperatively |
In chronic angle-closure eyes, there is an increased risk of malignant glaucoma |
Consider tighter scleral flap closure to avoid postoperative hypotony and shallow/flat anterior chamber |
Pseudophakic (Postoperative) Eyes |
Check conjunctival mobility prior to choosing a filter site |
Use caution when creating scleral flap through old cataract wound incision (risk of avulsion of scleral flap) |
Perform anterior vitrectomy for vitreous in the anterior chamber |
Use antimetabolites (mitomycin C or 5-fluorouracil) |
Systemic medications may also influence the outcome of filtration surgery. Anticoagulants and antiplatelet agents can add significantly to complications during and after filtration surgery. Excessive bleeding encountered during surgery may produce increased postoperative bleeding and scarring, which will make laser suture lysis of the trabeculectomy flap increasingly difficult and, at times, depending on the severity, impossible. These medications also increase the risk of suprachoroidal hemorrhage.9 Stopping all use of aspirin, aspirin-containing compounds, and nonsteroidal anti-inflammatory agents just before surgery is desirable, if medically safe. It may be helpful to instruct the patient to use only acetaminophen compounds only for the time prior to and immediately after surgery. In cases where blood-thinning agents are used long term for prophylaxis of specific medical conditions, it is advisable to consult with the patient’s internist before changing or withholding these medications. In many cases, it is possible to stop these for 1 to 2 weeks.
Coumadin is another commonly encountered anticoagulant. This medication has also been associated with increased risk of bleeding during and after surgery, and in general we recommend discontinuation of Coumadin (warfarin) 3 days prior to surgery and resuming it after surgery.10
These interventions described should always be considered within their clinical context. Adjusting systemic medications should only be entertained after consultation with the patient’s internist. In patients with far advanced optic nerve disease, where even short-term elevations of IOP may be hazardous to the patient, caution should be used when altering the medical regimen. On the other hand, reducing intraoperative and postoperative bleeding, inflammation, and scarring are important to long-term surgical success.
BASIC SURGICAL TECHNIQUE
Glaucoma filtration surgery is typically performed in either the superonasal quadrant or directly superior. This approach leaves a relatively undisturbed superotemporal quadrant if additional glaucoma surgery is required, such as a repeat filtration surgery or the use of a glaucoma drainage device.
What follows is a view of the step-by-step approach to modern guarded filtration surgery. It should become apparent that each step in the process of performing this surgery must be carefully considered.
Anesthesia
Retrobulbar anesthesia with lidocaine, bupivacaine, and hyaluronidase is effective for the majority of cases. Additional blocks that are used for lid akinesia, such as the modified van Lint or O’Brian, are often not necessary for filtering surgery. Retrobulbar anesthesia is preferred over peribulbar anesthesia that inflates the conjunctiva, rendering surgical dissection more difficult.
In cases in which extensive and/or numerous previous surgeries have been performed, obtaining satisfactory local anesthesia may prove problematic, and carefully monitored conscious sedation or general anesthesia maybe required. This is particularly true where prior scleral buckling surgery has been performed. In these cases, peribulbar scarring may prevent adequate anesthesia despite multiple injections. In such complex cases, good communication between the surgeon and the anesthesiologist is key to achieving a good anesthetic outcome.
Traction Sutures
Retracting the eye inferiorly is useful because surgery is usually performed in a superior quadrant.
The traditional approach is to use a superior corneal bridle suture. In this case, a 6-0 or 7-0 Vicryl (Ethicon, Inc) or silk suture on a spatulated needle is passed through clear, midstromal cornea approximately 1 mm from the limbus for approximately 2 to 2.5 mm. Gentle traction on the suture ensures its integrity prior to taping or clamping the suture to the inferior drape or having an assistant hold during the case. An alternative approach is to place an inferior corneal bridle suture. In this instance, the midstromal corneal suture is placed 1 mm above the inferior limbal margin. The suture is then placed beneath the inferior lid speculum. Gentle traction on the suture depresses the eye. In either case, it is essential that the suture does not pass into the anterior chamber, which produces a persistent aqueous leak at the suture site, hypotony, and a shallow anterior chamber during surgery, increasing the difficulty of the procedure and making mitomycin C (MMC) application hazardous.
An alternative approach is to use a superior rectus bridle suture for surgical exposure. The assistant gently sweeps the superior conjunctiva toward the limbus as the surgeon grasps the superior rectus muscle with 0.5-mm forceps. Using a 4-0 silk suture on a tapered needle, the surgeon places the suture beneath the superior rectus tendon. The suture is drawn superiorly and is clamped to the drape.
Corneal bridle sutures produce wide exposure of the superior conjunctiva. Additionally, inflammation or bleeding from manipulating the superior rectus and tenting of the conjunctiva in this region is avoided, making closure of the conjunctival flap easier. A potential disadvantage is the small area of corneal epithelial disruption at the suture site; however, this area is usually reepithelialized within 24 to 48 hours after surgery in the vast majority of patients.
Paracentesis
Placement of a paracentesis during filtration surgery just before the sclerotomy is essential. Most surgeons also wait until after application and rinsing of antifibrotic agent before making the paracentesis, thereby avoiding the risk, however small, of the medication entering the anterior chamber. A paracentesis permits the surgeon to gain access to the anterior chamber throughout the procedure. The paracentesis also allows the surgeon to reform the anterior chamber, test the function of the sclerectomy, check the relative seal of the scleral flap, and fill the conjunctival bleb to test for leaks at the end of the procedure. In cases where the IOP is very high, the paracentesis can be used early in the case to bring the IOP down gently, which prevents the eye pressure from rapidly plummeting when the sclerectomy is performed later in the procedure. Avoiding rapid decompression of the eye may help prevent the development of intraoperative suprachoroidal hemorrhage.
The paracentesis is typically placed temporally. It should be beveled, which makes the wound self-sealing. A side-port blade of the surgeon’s preference can be used. The blade is oriented tangential to the pupil to reduce the chance of lens injury. The orientation of the paracentesis and location should be carefully kept in mind by the surgeon for future access. A frustrating and not infrequent occurrence is the inability of the surgeon to locate the entrance. This problem can be easily alleviated by having the scrub technician paint the blade used for paracentesis with a marking pen. When the paracentesis is then performed, the epithelial entrance to the paracentesis is marked for the duration of the case and usually for the next 24 hours. Another frequent problem is successfully cannulating the paracentesis. This problem is compounded in the presence of a soft eye. The inclination to force a cannula through the paracentesis is tempting but futile. Suffice it to say, this approach does not work. Gently cannulating the paracentesis site in the correct orientation is essential to gain access to the anterior chamber. Additionally, it is important that the internal opening (endothelial side) is of adequate size. It is wise to cannulate the paracentesis immediately after it is made to ensure its patency rather than discover later that it is nonfunctional when it is needed and the eye is hypotonous. Although the paracentesis wound is usually self-sealing, it is important to check for a leak at the end of the case. If the paracentesis wound is leaking at the end of the case, then gentle hydration of the wound is recommended to obtain a watertight seal. Placement of a 10-0 nylon suture will be required if there is a persistent leak.
Creation of the Conjunctival Flap
The surgical management of the conjunctiva in filtering surgery is crucial to the long-term surgical outcome. This tissue will ultimately function as a fluid flow resistor. If IOP is to be in the normal range postoperatively, subconjunctival fibrosis,11 the most common cause of filtration failure, must be minimized. Therefore, excessive tissue manipulation should be avoided. Only nontoothed forceps should be used on this tissue.
The conjunctival flap may be either limbal or fornix based. Glaucoma surgeons have been divided as to which technique (fornix vs limbal based) they have adopted into their practice. There are strong advocates on either side, and in fact, some surgeons perform both techniques. We have found that both techniques have their advantages and disadvantages, and both have been found to be successful.12 Some advocate that limbal-based flaps tend to leak less and provide a lower postoperative IOP, where others suggest that fornix-based procedures are easier to perform and are less assistant dependent. Fornix-based flaps may also be necessary in cases where there is significant perilimbal scarring from previous surgical procedures. However, in our experience, careful conjunctival dissection and advancement during limbal-based surgery can still be successfully performed in an eye with conjunctival scarring.
Limbal-Based Flap
Limbal-based conjunctival flaps are less likely to leak postoperatively and, therefore, may be less likely to flatten and scar down. Usually, the postoperative posterior limit of the filtering bleb is demarcated by the conjunctival closure site. (However, with diffuse application of an antimetabolite such as MMC, the posterior limit of the bleb can often be the conjunctival closure site.) Therefore, it is necessary to make the initial incision through the conjunctiva as posterior as possible. A minimum of 8 mm is advisable (Figure 60-1). A Castroviejo caliper can be used to ensure that one does not enter the conjunctiva too anteriorly, because once done, the surgeon is committed. Once the conjunctiva is incised, Tenon’s fascia in turn is grasped and incised. This process continues until the episclera is visualized. The conjunctival wound should be lengthened to approximately 2 clock hours. The conjunctiva and Tenon’s tissue should only be incised when in the grasp of a forceps and while they are raised over the episclera. This precaution reduces the likelihood of accidentally incorporating a rectus muscle with these tissues, which is more likely to occur in cases where scarring from previous surgery is present or in some older individuals in which the superior rectus muscle has become more floppy and less apposed to the sclera.
The conjunctival-Tenon’s fascia flap is bluntly dissected to the limbus (Figure 60-2). If only a conjunctival flap is used, the bleb may subsequently become too thin. Meticulous hemostasis using tapered tip cautery is essential to prevent blood from collecting in the subconjunctival space where it can create adhesions between conjunctiva and episclera postoperatively. Caution to avoid too much cautery that could lead to burning of tissue and promotion of postoperative scarring should guide the surgeon as to the extent of cautery needed. Hydrodissection can be employed in cases where postoperative scarring is present from prior surgery. Hydrodissection helps define regions of conjunctival adhesion to the episclera. These sites are particularly prone to the development of buttonholes during blunt dissection and require gentle, deliberate sharp dissection. Blunt-tipped Westcott scissors are used to carry the dissection through the insertion of Tenon’s fascia (approximately 0.5 to 0.75 mm posterior to the limbus) to the insertion of the conjunctiva, which is about 0.5 mm onto clear cornea.
Fornix-Based Flap
Fornix-based conjunctival flaps are initiated with a 1.5 to 2 clock hour limbal peritomy. Blunt dissection is carried posteriorly using blunt-tipped Westcott scissors through the insertion of Tenon’s fascia (Figure 60-3). Hydrodissection may be useful to define areas of subconjunctival scarring when present. Blunt dissection is then carried posteriorly and laterally as far as the Westcott scissors can reach to obtain the most diffuse bleb possible. A common mistake during this step is to limit dissection to the area immediately posterior to the limbus. Success in achieving a shallow and diffuse bleb is enhanced with meticulous care in reaching a far nasal, temporal, and posterior dissection plane.
Tenon’s Capsule
The utility of performing a tenonectomy is still debated. Some surgeons find it aids in visualization of the sutures for lysis postoperatively; however, studies13,14 comparing a partial tenonectomy to no tenonectomy have shown comparable IOP reduction with either technique. If a tenonectomy is performed, it is generally easier using a limbal-based technique; however, with the fornix-based approach, it may be useful to remove at least the leading edge of Tenon’s fascia prior to suturing the flap to the limbus postoperatively. This helps to prevent wicking of aqueous through the flap and aids the conjunctival epithelium in healing and anchoring to the limbal stroma.
Creating a Scleral Flap
The sclera is an excellent barrier to fluid flow, and therefore, the scleral flap should not be considered a porous tissue that will function as a fluid filter in the mature bleb. Rather, the scleral flap, if adequately sutured, is a temporary resistor to the flow of aqueous through the sclerotomy site in the early postoperative period that reduces the incidence of hypotony. The shape of the scleral flap is of little consequence as long as the flap completely covers the sclerectomy. Our preference is to make a triangular flap 3.5 mm × 3.5 mm × 3.5 mm. A 15-degree blade can be used to create the margins of the flap as the globe is held in place with a 0.12-mm forceps. The flap is dissected anteriorly in a lamellar fashion with the same 15-degree blade, although some surgeons prefer a No. 57 or No. 69 Beaver blade.
The flap thickness should be at least one-half to two-thirds of the scleral thickness. Otherwise, the flap may be difficult to close or may avulse or tear during manipulation. The dissection is carried forward well beyond the gray line and into clear cornea, if possible (Figure 60-4). It is important to create a flap that is hinged as far forward as possible to ensure that the entry site for the sclerectomy is well anterior of the scleral spur and ciliary body. A paracentesis is then made, and the anterior chamber is filled with viscoelastic or balanced salt solution prior to creating the sclerectomy to prevent shallowing of the anterior chamber.
Sclerectomy
The sclerectomy is created by excising a block of tissue at the corneoscleral junction with the tissue punch or with scissors; each approach has its advocates. In either case, the anterior chamber is entered at the anterior-most point adjacent to the scleral flap with a 15-degree blade or other suitable sharp knife. If a block of tissue is to be excised, 2 radial incisions are made approximately 1.5 to 2 mm apart using Vannas scissors centered under the scleral flap. The block, now hinged posteriorly, is retracted posteriorly and excised with Vannas scissors. Frequently, the trabecular meshwork can be viewed directly while employing this procedure, which reduces the likelihood of bleeding as a result of inadvertent cutting into the ciliary body. Alternatively, a sclerectomy can be made with a Kelly-Descemet punch. Two to 3 punches may be required to make a sclerectomy of adequate size (Figure 60-5). The punch is technically easier to use. However, bleeding from small vessels in the angle is more common. Gentle cautery of small bleeders can be performed under direct visualization and preferably prior to making the iridectomy. In order to stop persistent bleeding, epinephrine 1:100,000 solution (sterile and unpreserved) can be used. If the iris balloons forward through the surgical opening at any time during the construction of the sclerectomy, a small radial snip of the iris with Vannas scissors can deflate the ballooning by allowing aqueous to escape and the iris to fall back into the anterior chamber. Completion of the sclerectomy with less concern of iris incarceration in the tissue punch can then be performed.
Iridectomy
A peripheral iridectomy is performed to prevent obstruction of the sclerectomy by the iris. It should be larger than the sclerectomy in all dimensions. Performing an iridectomy in a deliberate and careful manner is essential to prevent the undesired challenge of revising an inadequate iridectomy, which is difficult to do and can be hazardous. The iridectomy should be wide at its base but should not extend too far anteriorly, because this can result in monocular diplopia. The assistant should gently retract the scleral flap to permit an unobstructed view of the sclerectomy. The surgeon grasps the iris 0.5 mm from its root with 0.12-mm or Calibri forceps in the surgeon’s nondominant hand. The peripheral iris is retracted radially through the sclerectomy. The Vannas or Mini Westcott scissors, in the surgeon’s dominant hand, are opened enough to encompass the retracted iris (Figure 60-6), and in one smooth cut, the iridotomy is made. The iris is reposited with a stream of balanced salt or by closing and gently massaging over the scleral flap. Forceps are never used, as they may cause lens injury or vitreous loss. Upon completion of the iridectomy, the surgeon should have a view of the ciliary processes and, occasionally, the lens equator. If iris remnants or ciliary processes occlude the sclerectomy, these should be excised only with great caution. It is exceedingly easy to damage the lens or hyaloid face. Deepening the anterior chamber adjacent to the sclerectomy with viscoelastic material or balanced salt solution through the paracentesis is a useful maneuver to give the surgeon working space in these situations.
SCLERAL FLAP CLOSURE
The scleral flap should be closed tightly enough to prevent postoperative hypotony. It is generally easier to cut or release sutures when the IOP is higher than desired than to deal with the complications related to prolonged low postoperative IOP. The flap is closed with interrupted 10-0 nylon sutures. A 3-1-1 knot buries well and secures the flap adequately. Usually, 3 to 5 sutures are used to close a triangular flap (Figure 60-7), and 2 to 4 sutures are used for a rectangular flap. Once the flap is secured, it is wise to reform the anterior chamber through the paracentesis with balanced salt solution and bring the eye up to an adequate IOP. In this way, the integrity and function of the scleral flap can be assessed using a Weck-cell sponge. If the IOP and anterior chamber depth are maintained with slow oozing of aqueous humor, then scleral flap closure is usually adequate. However, if aqueous humor flows freely and the anterior chamber shallows, additional sutures are required.
On the other hand, if the IOP is high and aqueous does not flow through the flap, sutures should be loosened or removed and replaced. If aqueous humor still does not flow, it may be necessary to reopen the scleral flap and inspect the sclerectomy to ensure it is not obstructed.
Conjunctival Closure
Watertight conjunctival closure using nontoothed forceps is necessary to create an elevated filtering bleb. Tissues should be brought to apposition only. Tight sutures cheese-wire, or tear through the tissue, postoperatively, creating a leaky, inflamed wound. Meticulous closure of the conjunctiva can save many postoperative hours dealing with the complications related to poorly closed wounds.
Limbal-Based Flap Closure
Limbal-based flaps are closed in a variety of ways. However, most surgeons currently favor the use of running conjunctival closures with 8-0 or 9-0 absorbable suture (eg, Vicryl) on a blood vessel needle. Beginning on the side of the surgeon’s dominant hand, the Tenon’s fascia is closed with a running suture followed by the conjunctiva in the same manner. It is useful to lock the running suture every second to third throw to provide watertight closure. Care should be taken not to take large bites of the anterior Tenon’s or conjunctiva, as this may cause the wound to migrate anteriorly and create unwanted tension on the limbal conjunctiva. After closure of conjunctiva (Figure 60-8), the wound is checked with a Weck-cell for watertight closure. At this point, many surgeons irrigate the anterior chamber until a small bleb forms. This is to ensure adequate flow is established.
Fornix-Based Flap Closure
Fornix-based flaps can be closed in a watertight manner as well. Closure with winged sutures using nylon or Vicryl at either end of the conjunctival flap may position the leading edge of the flap over the limbus but may not offer a watertight closure in the early postoperative period. This can produce a lower, more circumscribed bleb postoperatively and delay the use of 5-fluorouracil (5-FU) if it is needed. If conjunctival wing sutures prove inadequate for watertight closure of a fornix-based flap, 3 or 4 long mattress sutures are placed at the limbus using 10-0 nylon or 8-0 to 10-0 Vicryl on a spatulated needle. The suture should be placed through midstromal cornea. In order to avoid cheesewiring, the sutures should not be tied too tightly. Typically, the sutures become buried in conjunctival tissues and cause no postoperative discomfort. Exposed nonabsorbable sutures are removed after wound healing has occurred.
Some surgeons have used other techniques that may help to decrease the incidence of early postoperative bleb leaks in fornix-based flaps. Debriding a 1- to 1.5-mm zone of limbal corneal epithelium by gentle abrasion with a knife or by using cautery promotes adhesion of the conjunctival flap to the corneal stroma. Trimming Tenon’s fascia from beneath the leading edge of the conjunctival flap may help to prevent wicking of aqueous humor under the anterior flap edge.
Fluorescein testing for bleb leaks should be performed at the conclusion of fornix-based surgery. This can be done after the anterior chamber has been reformed with balanced salt solution and the bleb has been inflated. Either 2% fluorescein sodium solution or a saturated fluorescein strip is placed on the conjunctival closure covering this region in dense orange. A leak is readily apparent as an area of greenish flow in a sea of orange. If a bleb leak is detected, it should be closed with a single suture or a horizontal mattress suture and the wound rechecked with fluorescein. A beveled paracentesis site rarely leaks; however, if a persistent leak does occur, a single interrupted 10-0 Vicryl or nylon suture should be placed.
Conjunctival Buttonholes
Buttonholes can generally be avoided by meticulous handling of the conjunctiva with nontoothed forceps. Where they are more likely to occur is where there is conjunctival scarring from previous surgery or trauma, or where excessive traction has been used in an attempt to improve exposure of the surgical site. If a large buttonhole is found that overlies the filter site early in the case, the surgeon should consider relocating the filter to the adjacent quadrant.
It is frequently best to repair buttonholes after completing the planned filtration surgery. By delaying it to the end of operation, it is less likely that the conjunctival repair will be weakened. However, where there is a buttonhole, the surgeon must be especially cautious not to extend it during the operative procedure.
The manner of repair depends on the location of the buttonhole. If the edges of the buttonhole are within the conjunctiva, a horizontal mattress suture that includes both conjunctival margins and Tenon’s fascia is effective. Absorbable 10-0 Vicryl suture on a tapered vascular needle is preferred. When closed, the inner conjunctival wound margins should be well apposed.
If the buttonhole is located at the limbus where no conjunctiva is available on the corneal side of the buttonhole, a horizontal mattress suture is placed that includes peripheral cornea and the edges of the conjunctiva. Prior to closing the buttonhole, the peripheral corneal epithelium may be abraded or removed by gentle cautery to promote adhesion of the conjunctiva to the cornea. A 10-0 nylon suture on a tapered needle or an absorbable suture can be used. Tapered needles are fragile and bend easily. However, if the needle is grasped closer to the point, it is usually possible to pass the needle through the superficial cornea.
Once the conjunctival flap closure is complete, the anterior chamber is filled with balanced salt solution, and the bleb is elevated. Watertight closure of the buttonhole repair and the conjunctival wound is tested with fluorescein.
Conclusion
At the conclusion of filtering surgery, subconjunctival dexamethasone phosphate 5 mg may be injected opposite the site of the filtering bleb. Injectable antibiotics can be used, but some surgeons feel it may increase postoperative inflammation. Cycloplegics (eg, atropine 1%, homatropine 5%, or scopolamine 0.25%) are used if the patient is still phakic or has a shallow chamber to begin with. This is followed by a combination steroid/antibiotic ointment (eg, Tobradex or Maxitrol), which is then applied. The eye is then gently patched and an eye shield applied.
IMMEDIATE POSTOPERATIVE MANAGEMENT
The postoperative period following glaucoma filtering surgery is frequently challenging (see Chapter 61). This is largely because surgery is only the initial step in a long process that culminates in an alternative functional drain for aqueous humor. In order to be successful, the surgeon must frustrate the natural healing process while attending to fluctuations of IOP in the operated eye and not infrequently the fellow eye as well. Due to the number of events transpiring in this period, frequent examinations are required.
The Fellow Eye
Postoperatively, there could be changes in the medical regimen that may affect the IOP in the fellow eye. This would be the case if a patient had uncontrolled IOP in both eyes that necessitated the use of an oral carbonic anhydrase inhibitor (CAI) prior to performing surgery in one eye. In this scenario, the benefit of continued oral CAI to protect the nonsurgical eye must be balanced against the risk of hypotony or failure of the newly created filtering site in the surgical eye. It might be beneficial or even necessary to proceed with surgery in the second eye soon after the surgery in the first eye.
Unintentional noncompliance may occur due to major changes in the patient’s drug regimen. A medication chart is very useful for patients who may be taking half a dozen different drops with varying dosing schedules. Having patients describe how they are actually taking their medication can be illuminating as well. On rare occasion, topical steroids in the operated eye may produce a crossover effect on IOP in the fellow eye.15–17 This is due to ocular venous absorption of topical medications bypassing the first-pass effect of liver enzymes that orally administered medications encounter. This phenomenon via application of ophthalmic steroids is not universally agreed upon,18 but given the possibility of a response, it is essential to monitor postoperative IOP in both eyes following unilateral surgery.
If the IOP reaches unsafe levels in the fellow eye, the surgeon must advance therapy accordingly. The introduction of additional topical medications may be useful. Laser or surgical intervention may ultimately be necessary. Although the prospect of additional surgery is stressful to the patient, it is important to prevent progressive optic nerve damage from occurring in the fellow eye during this time period.
ANTIPROLIFERATIVE THERAPY FOR FILTRATION SURGERY
Mahmoud A. Khaimi, MD; Marcos Reyes, MD; and David Anson Lee, MD, MS, MBA
The purpose of glaucoma filtration surgery is to bypass the pathological obstruction of the outflow channels of the eye in order to decrease the IOP to a level low enough to prevent progressive damage to the optic nerve. Glaucoma filtration surgery does not directly address the causes of the abnormalities in aqueous humor outflow and cure glaucoma. However, it does lower the IOP by a more physiological mechanism than by decreasing the inflow of aqueous humor into the eye as is done by many of the topical and systemic antiglaucoma medications. It is arguable whether glaucoma filtration surgery should be performed early in the treatment of glaucoma, even before the use of antiglaucoma medications. The surgical treatment of glaucoma does have its risks that may be greater than those from medical therapy.
A major risk of glaucoma filtration surgery is failure due to obstruction of drainage of aqueous humor through the surgical site. This obstruction is most commonly due to the normal ocular wound healing response to surgical injury. The end result is formation of scar tissue, which blocks the passage of aqueous humor from the surgical area. Conditions that may increase the risk of failure of glaucoma filtration surgery include previously failed glaucoma surgery, aphakia or pseudophakia, uveitis, neovascularization, youth, or Black ethnic background.
To improve the success of glaucoma filtration surgery and limit scar tissue formation, it is important to understand the basic mechanisms of the wound-healing response. The wound-healing response is essential to the survival of all living organisms and has evolved over millions of years. It is a complex and time-limited series of events that begin when tissue is injured.1 The initial event is coagulation and vasoconstriction to stop the bleeding. This is immediately followed by inflammation with the entry of white blood cells into the injured area and the release of enzymes and cytokines to prevent infection and initiate the wound-healing process. Epithelial cells, macrophages, and fibroblasts migrate into the injured area to begin closure of the wound and tissue repair. Granulation tissue forms and is composed of vascular endothelial cells that deliver a new blood supply to nourish the rapidly dividing fibroblasts. These events occur within the first several days following injury. Over the following weeks, as the inflammatory process subsides, the fibroblasts produce and secrete collagens and other extracellular matrix proteins that are the major components of scar tissue. The collagen becomes cross-linked, and remodeling occurs as the scar tissue matures over the following months and the wound healing process concludes. The remaining scar tissue that is impermeable to aqueous humor causes failure of glaucoma filtration surgery.
Tissue culture and animal models have been used to better understand and control the complex wound-healing process. Tissue culture models can quantitatively study isolated aspects of fibroblastic activity (attachment, migration, proliferation, and extracellular matrix protein synthesis) relatively rapidly and inexpensively. However, the immune and vascular systems important to wound healing cannot be accurately duplicated in tissue culture. The most commonly used animals to model glaucoma filtration surgery and ocular wound healing are monkeys and rabbits because of similarities in ocular size and anatomy to human eyes. However, both of these animal species have a more rapid and aggressive ocular scarring reaction following glaucoma filtration surgery than humans, and the results in an animal model may not be totally applicable to humans. Both tissue culture and animal models have been used to test the efficacy, safety, and proper concentrations of wound healing inhibitory agents before their use in human eyes.
Many attempts have been made to minimize the scarring and improve the success of glaucoma filtration surgery including modifications of surgical technique, drainage devices, and medications. Various medications can affect the different stages of the wound-healing process. Some of the earliest and most commonly used agents were topical corticosteroids that inhibit the initial ocular inflammatory response following surgery. These agents are very efficacious, but are frequently not sufficient to prevent the scar tissue growth that causes surgical failure. Antiproliferative agents that inhibit the growth of living cells have been used for the treatment of cancer for many years and for the prevention of ocular scar formation for more than 15 years. They have been used to treat proliferative vitreoretinopathy as well as to prevent scarring after glaucoma filtration surgery.
The first antiproliferative agent used following glaucoma filtration surgery was 5-FU.2 It was later used intraoperatively and then followed by weekly injections. This agent acts selectively during the synthesis phase of the cell cycle to inhibit DNA synthesis. The metabolites of 5-FU are even more potent than the original drug in inhibiting cell proliferation. This agent was originally administered as a subconjunctival injection following surgery at a dose of 5 mg in 0.5 mL twice daily in the first postoperative week and once a day in the second postoperative week, for a maximum total dose of 105 mg. The subconjunctival injections were given with a 30-gauge needle 180 degrees from the surgical site after local anesthesia was induced using a cotton pledget soaked with proparacaine or cocaine. This regimen was found to significantly improve the success rate of glaucoma filtration surgery in eyes at high risk for failure from 26% in the standard treatment group to 51% in the 5-FU treatment group after 3 years of follow-up. Complications from this treatment include corneal epithelial defects, conjunctival wound leaks, and bleb ruptures. The frequency and amounts of 5-FU have been titrated according to clinical response, and lower doses (ranging from a total amount of 17.5 to 62.5 mg given in 2 to 12 injections) may be as effective as the original regimen with fewer adverse side effects.
MMC is almost 100 times more potent than 5-FU in inhibiting fibroblast proliferation and is not cell cycle specific, inhibiting DNA-dependent RNA synthesis. It may also have antiangiogenic effects on blood vessels and toxicity to the ciliary epithelium and its nerve supply. These effects may account for the conjunctival avascularity and hypotony seen after MMC is used during glaucoma filtration surgery. This agent is usually administered at the time of surgery using a Weck-cell sponge saturated with 0.2 to 0.4 mg/mL of MMC and placed between the sclera and conjunctival flap for 2 to 5 minutes.3 The sponge is then removed, and the exposed area is irrigated with 15 to 250 mL of balanced salt solution to minimize toxic effects. Alternatively, MMC can be injected in the superior sub-Tenon’s space at a much more dilute concentration (0.05 to 0.1 mg/mL) at the beginning of the case. The injected bolus of MMC is then spread around the superior conjunctiva and Tenon’s layer with a muscle hook. Complications from MMC are similar to 5-FU and also include chronic hypotony and maculopathy.
Other antiproliferative agents are currently under investigation that may be safer, more potent, or more specific for the cells actively involved in the wound-healing process. A key challenge is to find an agent, or more likely a group of agents, that selectively acts on those cells that produce or assist in the production of scar tissue and physiologically regulates their behavior. Perhaps the most promising agents are cytokines or antibodies to cytokine receptors that are able to affect collagen synthesis without interfering with other normal cellular activities.4 After these agents are identified, there is the further challenge of delivering them to their intended site of action at the most effective concentration and at the proper duration. Novel drug delivery systems include liposomal-based delivery systems5,6 and synthetic polymers of various shapes and sizes. An ideal system would provide nontoxic, localized, and sustained delivery of the agent(s) of choice in a properly timed sequence, and it would eventually disappear to avoid any foreign body complications.
Understanding and addressing the basic mechanisms of the ocular wound-healing response are the best ways to improve the success and safety of glaucoma filtration surgery.
REFERENCES
1. Tahery MM, Lee DA. Pharmacologic control of wound healing in glaucoma filtration surgery. J Ocul Pharmacol. 1989;5:155-179.
2. The Fluorouracil Filtering Surgery Study Group. Three-year follow-up of the fluorouracil filtering surgery study. Am J Ophthalmol. 1993;115:82-92.
3. Chen CW, Huang HT, Bair JS, et al. Trabeculectomy with topical application of mitomycin-C in refractory glaucoma. J Ocul Pharmacol. 1990;6:175-182.
4. Nguyen KD, Hoang AT, Lee DA. Transcriptional control of human Tenon’s capsule fibroblast collagen synthesis in vitro by gamma-interferon. Invest Ophthalmol Vis Sci. 1994;35:3064-3070.
5. Maigenen F, Tilleul P, Billardon C, et al. Antiproliferative activity of a liposomal delivery system of mitoxantrone on rabbit subconjunctival fibroblasts in an ex-vivo model. J Ocular Pharmacol Ther. 1996;12(3):289-298.
6. Mietz H, Welsand G, Krieglstein GK, et al. Gene therapy to modulate wound healing following trabeculectomy: transfection of Tenon fibroblasts with oligonucleotides. Invest Ophthalmol Vis Sci. 2003;44.