Albert & Jakobiec's Principles & Practice of Ophthalmology, 3rd Edition

CHAPTER 220 - Glaucoma Filtration Surgery: Indications, Techniques, and Complications

Peng Tee Khaw,
Mark Chiang,
Peter Shah

INTRODUCTION

Current treatments of glaucoma are directed toward lowering the intraocular pressure (IOP), the major modifiable risk factor associated with the disease. Despite recent advances in glaucoma detection and medical therapy, a percentage of patients with severe potentially blinding glaucoma still require surgical intervention for IOP control. Surgery may also be the most practical glaucoma therapy in many underdeveloped countries.

The field of glaucoma filtration surgery (GFS) is constantly changing. Trabeculectomy, introduced by Cairns in 1968, revolutionized glaucoma surgery and still remains today as the 'gold standard' GFS for many types of glaucoma.[1] The operation of trabeculectomy aims to create a permanent drainage outflow channel for aqueous humor, connecting the anterior chamber to the sub-Tenon's space. Trabeculectomy differs from most surgical procedures in that the inhibition of postoperative wound healing can greatly enhance its success. Failure of trabeculectomy can occur as a result of scarring at the site of the new drainage channel with subconjunctival/Tenon's fibrosis and fibrosis at either the level of the scleral flap or ostium. Traditional trabeculectomy surgery also has a substantial risk profile including postoperative hypotony, bleb-related problems and endophthalmitis, all of which may lead to permanent visual loss.

Driven by the need to achieve lower target IOPs whilst minimizing complications, significant modifications to the original trabeculectomy technique have evolved.

The following key areas will be addressed:

1.

The evolution of trabeculectomy including the rationale for new developments

2.

The pre-, intra-, and postoperative strategies for trabeculectomy

3.

Complications of trabeculectomy

4.

Emerging techniques in GFS

Although in this chapter we have focused on trabeculectomy many of the discussions are relevant to other types of filtration surgery.

PREOPERATIVE MANAGEMENT IN GFS

DECISION TO OPERATE

GFS was previously performed when patients had uncontrolled IOP on maximally tolerated medical treatment, or after failed laser trabeculoplasty. The main reasons for delaying surgery were the risk of postoperative complications associated with traditional trabeculectomy and the high failure rates seen in high-risk subgroups. However, with new GFS developments leading to increased safety profile and surgical success, early GFS may be performed in patients with:

1.

Advanced visual-field defect (including central scotomas) at presentation

2.

Rapidly progressive visual-field loss

3.

Intolerance to medical therapy

4.

Noncompliance

5.

Low target IOP unlikely to be achieved with medical and/or laser therapy - There is established evidence that lowering IOP to the range of 10-15 mmHg has a protective effect in advanced glaucoma and normal tension glaucoma (NTG).[2-4]

Success of GFS is highly dependent on patient motivation and cooperation. Therefore it is essential that the implications of failed or complicated surgery are carefully considered on an individual basis and factored into the surgical plan. This is particularly relevant in only eye surgery, advanced disease and young patients. Several issues must be addressed, including:

1.

Tolerance of anesthesia

2.

Life expectancy

3.

Occupation

4.

Cultural, religious and social deprivation issues

5.

Educational status

6.

Ability to attend frequent postoperative clinic appointments

7.

Family/work/school commitments

8.

Pregnancy and lactation status

It is essential that the surgeon and patient have common goals and realistic achievable expectations.

CHOICE OF TECHNIQUE

The choice of GFS technique with or without adjuvant antifi-brotic agents should be determined by balancing the target IOP and risk factors for GFS failure against the risk factors for complications (Fig. 220.1). This is particularly important as antifibrotic agents including MMC have been associated with increased complications.[5-9] The titrated use of antifibrotic agents allows modulation of the postoperative scarring response, the degree of subconjunctival and sub-Tenon's fibrosis, and hence the ability of GFS to allow adequate aqueous drainage and then reabsorption into the episcleral vasculature. Current antifibrotic modalities include MMC, 5-fluorouracil (5-FU) and beta radiation. Extensive investigation using animal models has provided helpful guidance on appropriate titration of individual treatments.[10,11]However, there is no universally accepted regime in human populations. This may reflect the fact that significant variations exist between surgeons in terms of surgical technique, glaucoma case-mix, ethnicity, personal experience and training, and availability of treatment options. The regimen we use called Moorfields Florida More Flow regime is an example of this and is presented later in the chapter.

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FIGURE 220.1 Risk stratification model.

CHOICE OF ANESTHESIA

The various operations described in this chapter can be carried out under local anesthesia (LA) or general anesthesia (GA). The essential intraoperative requirements of trabeculectomy are an immobile and anaesthetized eye, minimal bleeding, low vitreous pressure and a comfortable patient.[12] There are specific anesthetic points to take into account when performing glaucoma surgery.

General Anesthesia

GFS is an effective method of lowering IOP in potential blinding disease. GA has potential advantages in GFS:

1.

Many patients including the young, the anxious and those with altered mental status or language barrier tolerate local anesthesia poorly.

2.

General anesthesia allows maximal control of the operative conditions - optimal systemic blood pressure control can be achieved to assist hemostasis and maneuvers such as hyperventilation can be performed to minimize choroidal expansion (e.g., young patients, Sturge-Weber syndrome). LA may increase the tension on the conjunctiva and Tenon's capsule leading to posterior tissue retraction. This can make the subsequent wound closure difficult.

3.

There is an increased risk of globe perforation using sharp needle techniques in large eyes. Fluid in the retrobulbar space may compromise the nerve, particularly one with advanced glaucomatous neuropathy.

4.

LA techniques which involve the violation of conjunctiva/Tenon's may increase the risk of postoperative bleb fibrosis - there is some evidence that subconjunctival anesthesia increases trabeculectomy failure.[13]

However, the risks of GA must be weighed against patient's general medical condition, as patients with glaucoma often have multiple systemic co-morbidities.

Local Anesthesia

When performing GFS under LA it is important to avoid unnecessary elevation of IOP. It may be necessary to paralyze orbicularis oculi in patients with significant eyelid squeezing.

Peribulbar anesthesia and retrobulbar anesthesia

Peribulbar anesthesia (PBA) is the most commonly used LA technique for GFS. Both PBA and retrobulbar anesthesia (RBA) are associated with elevated IOP and reduced ocular blood flow which is potentially blinding for patients with end-stage glaucoma.[12,14] In these cases, reduced volumes of LA agents with hyaluronidase can be used, and orbital compressive devices (e.g., mercury balloons) are best avoided. In eyes with increased axial length (e.g., myopes, buphthalmos and eyes with posterior staphyloma), there is an increased risk of ocular perforation. Patients should be warned about a transient enlargement of their scotoma with RBA. In an only eye, this may render the patient effectively blind for many hours - G A may be preferable in these cases and has the additional benefit of increased intraoperative control.

Sub-Tenon's anesthesia

Sub-Tenon's anesthesia (STA) is considered safer than PBA/RBA because a sharp needle is not used. The development of akinesia using STA relates to the direct spread of LA agents into the Tenon's sheaths surrounding the extraocular muscles. STA may cause less discomfort during injection compared to PBA/RBA. Potential disadvantages of STA include unreliable akinesia, discomfort during iridectomy, diathermy and conjunctival closure and very rarely, globe perforation.[12] STA is also associated with chemosis and subconjunctival hemorrhage. Chemosis can cause posterior retraction of the Tenon's capsule and make conjunctival closure difficult. Subconjunctival hemorrhage may promote fibrosis and increase the risk of GFS failure.

Subconjunctival anesthesia

Subconjunctival anesthesia is less commonly used in GFS and has been associated with increased GFS failure.[13] Subconjunctival injection may cause scarring due to hemorrhage and tissue damage. One study reported eye movements in 47% of patients, intraoperative pain in 20% and subconjunctival hemorrhage in 7% when subconjunctival anesthesia was used in GFS.[15]

Topical and intracameral anesthesia

Topical plus intracameral anesthesia is being adopted for GFS as it avoids injection pain, conjunctival damage, chemosis, subconjunctival hemorrhage and the increased IOP seen in PBA/RBA. However, topical anesthesia may be unsuitable in prolonged procedures due to inadequate tissue concentration and intraocular penetration. Therefore additional intravenous sedation or change of anesthesia method during GFS may be necessary. The supplemental use of intracameral anesthesia allows intraocular structures such as the iris to be anesthetized, but the injection carries the risk of damaging the lens and causing pupil dilatation. The main limitation with topical anesthesia with/without intracameral supplementation is the lack of akinesia.

PREOPERATIVE CONSULTATION AND CONSENT

The risks of any form of surgery should be explained to the patient in advance. It is vital to explain that the aim of GFS is to preserve vision, not to improve it. The possibility of blurred vision in the early postoperative period and the rare complication of losing the remaining visual field ('wipeout') should be discussed. Contact lens users should be advised that contact lens use may not be possible after GFS. Other potential blinding complications such as suprachroidal hemorrhage and endophthalmitis should also be mentioned. The patient must understand the need for frequent postoperative follow-up and the lifestyle changes required in the first few months after GFS. The use of medications which predispose to bleeding such as aspirin, clopidogrel, warfarin and herbal remedies such as Gingko Biloba should be established. They should be ceased preoperatively if medically feasible. A-scan ultrasonographic measurement should be made to identify eyes with short or long axial length and thin or thick sclera if possible. One of the key components of a patient's perception of a successful operation is good management of patient expectation. It is vital elicit a patients expectation of the operation and manage this proactively.

PREOPERATIVE STRATEGIES

Preoperative Medical Treatment

Steroids

It has been shown that chronic preoperative topical treatment jeopardizes filtration surgery by increasing the number of fibroblasts and inflammatory cells in the conjunctiva.[16] This is particularly marked in association with the long-term use of adrenergic agents which cause conjunctival inflammation such as adrenaline and dipivefrin. Topical steroids such as fluo-romethalone 0.1% 4 times daily for 30 days preoperatively reversed the histological changes in the conjunctiva, although whether this conclusively increases the success rate has not been proven.[17,18] In uveitic glaucoma, additional immuno-suppression using oral and/or intravenous steroid and sometimes nonsteroidal systemic immunosuppression may be required to ensure optimum control of ocular inflammation prior to surgery.

Non steroidal antiinflammatory drugs

The use of preoperative non steroidal antiinflammatory drugs (NSAIDs) such as indomethacin or flurbiprofen has not been proven to alter the long-term results of glaucoma filtration surgery. However, in patients who may require iris manipulation and at risk of fibrinous uveitis (especially dark irides), preoperative topical steroids and nonsteroidal drops for as short as 24 hours may be beneficial.

Medical Treatment at the Time of Surgery

Sympathetic agonists

Topical apraclonidine hydrochloride (Iopidine) 1%, a relatively selective ?2-agonist, can be used ?30 min before the operation.[19] It has a potent vasoconstrictive activity in the anterior segment tissues of the eye. Blood contains many growth factors that promote wound healing and increase the chance of filtration surgery failure. Excellent hemostasis during conjunctival and sub-Tenon's dissection, scleral flap construction and peripheral iridectomy can be achieved. Additional benefits of topical apraclonidine 1% instead of adrenaline include the avoidance of mydriasis and the potential to prevent early postoperative IOP spikes.

Topical epinephrine 0.01% can also be used at the beginning of the operation. This produces conjunctival vasoconstriction and a reduction in bleeding during the course of the procedure. The disadvantages of using epinephrine include pupillary dilatation and rebound hyperemia.

Povidone-iodine

Povidone-Iodine has a broad spectrum of antimicrobial action. It can be used to prepare the skin, and drops can be applied to the superior and inferior fornix. This is particularly important if the patient has preexisting conjunctival or lid disease, which predisposes to bacterial colonization.

Parasympathetic agonists

Pilocarpine eye drops are rarely used now for miosis. This theoretically protects the cornea from lens-corneal touch and may reduce the chance of inadvertently cutting an excessively large iridectomy. The disadvantages include shallowing of the anterior chamber (AC) and increasing the risk of malignant glaucoma, and a theoretical possibility that the blood/aqueous barrier may be further compromised. Preoperative long acting anticholinesterase agents should be discontinued if possible to reduce blood vessel congestion and leakage.

INTRAOPERATIVE MANAGEMENT IN TRABECULECTOMY

EVOLUTION OF TRABECULECTOMY

The introduction of trabeculectomy by Cairns in 1968[1] revolutionized GFS. The original description of trabeculectomy involved the use of a superior rectus suture, a limbal-based conjunctival flap and either a limbal-based or fornix-based scleral flap with preplaced sutures. The aim of the operation was to excise a block of Schlemm's canal and trabeculum allowing free aqueous drainage into the exposed ends of the canal of Schlemm, hence the name trabeculectomy. It was originally never intended to make a fistula to result in a drainage bleb. The presence of a drainage bleb, although resulting in lowered intraocular pressure, was in fact regarded as a surgical failure in the original series. Over the next few years after the initial description, it was found that the presence of a drainage bleb tended to be associated with an increased success rate.[20-23] As a result, trabeculectomy began to be regarded as filtration surgery and more attention was focused on surgical techniques which facilitated the creation of diffuse drainage blebs. However, the diversion of aqueous from the intraocular to the extraocular compartment brought many complex technical difficulties.

The driving force behind the subsequent advances in trabeculectomy can be divided into two broad categories:

1.

Prevention of trabeculectomy failure - the management of postoperative fibrosis.

2.

Prevention of complications including postoperative hypotony, infection and bleeding - developments to prevent over-drainage, postoperative wound leaks and poor bleb morphology.

SURGICAL TECHNIQUES

Position of Filtration Area

Glaucoma filtration surgery (GFS) is most commonly performed at a superior site, so that the upper lid protects the drainage area. A peripheral iridectomy placed at 12 o'clock is also covered by the lid, and does not give rise to diplopia. Drainage blebs that are not covered by the upper lid, particularly those in the interpalpebral aperture or the lower fornix, have up to a 10 times greater incidence of inflammation and endophthalmitis especially with the use of antifibrotics.[24] Surgically-induced scleritis may also be more common when the bleb is not placed superiorly. Recurrent subconjunctival hemorrhage has been reported with the drainage bleb extending beyond the lid margin.[25] and significant bleb discomfort and pain is much more common with interpalpebral blebs. Therefore it is important to position the bleb with maximal upper lid coverage. Other surgical procedures should be considered if this is not possible.

Traction Suture

Superior rectus traction sutures have been used for many years to provide infraduction in ophthalmic surgery, however, they may cause retinal and globe perforation,[26,27] retrobulbar hemorrhage,[28]postoperative ptosis,[29,30] superior rectus hematoma, subconjunctival hemorrhage and patient pain and discomfort.[31] Subconjunctival hemorrhage or superior rectus hematoma may induce the release of growth factors which in turn trigger the unwanted wound healing response in trabeculectomy. The use of superior rectus traction sutures had been associated with reduced trabeculectomy success.[13] The corneal traction suture technique in this chapter was described by Conklin et al in 1991 in an attempt to prevent the potential conjunctival damage and bleeding caused by superior rectus traction sutures.[32]The vector force of the corneal suture is superior to that achieved with a superior rectus suture. The disadvantages of the corneal traction suture include the small risk of placing the suture too deeply and penetrating the AC (particularly buphthalmic and highly myopic eyes), and the chance of placing the suture too superficially with subsequent 'cheese-wiring' and loss of traction. A variety of sutures can be used, but the authors use a 7-0 black silk suture on a semicircular needle (Fig. 220.2).

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FIGURE 220.2 Corneal traction suture provides better exposure and no secondary subconjuctival hemorrhage.

Conjunctival Incision

Two types of conjunctival incisions can be made to gain access to the operative site:

.

Limbal-based conjunctival flap (LBCF) - incision deep in the fornix with the base at the limbus

.

Fornix-based conjunctival flap (FBCF) - incision at the limbus with the base in the fornix

The LBCF was introduced by Cairns in his original description of trabeculectomy.[1] The FBCF was first described by Luntz in 1980[33] who proposed that this approach was technically easier, offered better visualization during scleral flap construction and resulted in more diffuse and posteriorly draining blebs. In 1984, Shuster et al compared LBCF and FBCF and demonstrated similar surgical success, but with increased early postoperative wound leaks using FBCF. Despite this finding, the use of FBCF may offer advantages particularly important in glaucomas associated with poor surgical success.[34]

More studies in the late 1980s examined the difference between LBCF with FBCF.[35-37] Agbeja and Dutton[35] assessed posttrabeculectomy bleb morphology and found more diffuse drainage blebs without increased wound leaks in the FBCF group. Bleb morphology in the study did not affect IOP control. Grehn et al[37] found no difference in terms of IOP control, bleb morphology, visual-field changes and visual acuity between the two techniques. Another study suggested better IOP control with LBCF but the study suffered from possible sample bias.[36] With the introduction of antiscarring agents especially MMC, fears concerning the tendency for postoperative wound leaks using FBCF arose. Henderson et al[38] found by applying pressure to the drainage bleb, the FBCF group had significantly more leaks than the LBCF group (65% vs 24%). Despite the increased early postoperative leaks with FBCF, the outcome was not adversely affected. Alwitry et al compared the outcomes of augmented trabeculectomy with MMC using LBCFs and FBCFs and found no difference in IOP control, rate of aqueous leakage and the need for intervention or glaucoma medications.[39]

However the advent of antimetabolites accentuated the differences between the two approaches. We proposed, based on clinical observation two phenomena necessary for cystic blebs - anterior aqueous drainage and a ring of scar tissue coined the 'ring of steel.' LBCF was more likely to result in a cystic bleb when the surgical incision was not posterior enough. It was technically easier to achieve a larger area of MMC treatment with a FBCF which prevented the 'ring of steel' (Fig. 220.3) We studied the postoperative bleb morphology in young patients undergoing trabeculectomy with high dose MMC and reported significantly more cystic blebs using LBCFs (90%) compared to FBCFs (29%) with a marked reduction in bleb related complications including leakage, blebitis and endophthalmitis.[40] The advantages and disadvantages of both FBCF and LBCF are summarized in (Table 220.1).

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FIGURE 220.3 Exploration of a cystic bleb showing predisposing factors for cystic bleb formation-'a ring of scar tissue we have named the 'ring of steel' and anteriorly directed aqueous flow.


TABLE 220.1 -- Advantages and Disadvantages of Fornix-Based and Limbal-Based Conjunctival Flaps

Fornix-Based Conjunctival Flap

Limbal-Based Conjunctival Flap

Technical difficulty

Easier and faster to perform

More difficult and takes longer to perform

Exposure of operative field

Good exposure allowing good visualisation of sclerostomy and easier 'releasable' suture placement

Not as good, less visualisation of sclerostomy and reflected conjunctiva may make releasable sutures difficult

Area to be dissected

Smaller

Larger

Antifibrotic application

Need great care on insertion, may need more sponges

Easier antifibrotic application

Re-operation

Easier

More difficult due to extensive scarring

Bleb morphology

More diffuse posteriorly draining blebs

May get more cystic blebs and 'ring of steel' with more anterior drainage

Conjunctival wound leakage

May have higher incidence but published results variable

May have less wound leakages

General principles in conjunctival flap creation

Handling of the conjunctiva must be gentle and kept to the minimum to avoid buttonholing, particularly if antifibrotics are used. If the tissues are particularly thin and prone to tearing, stromal hydration can be performed early by injecting balanced salt solution (BSS) via a Rycroft cannula underneath the conjunctiva and Tenon's into the region of the future bleb to hydrate the tissues, making them thicker and easier to handle. In both LBCF and FBCF, hemostasis is important by using minimal wet-field diathermy (unipolar or bipolar) to the sclera to prevent tissue damage and shrinkage.

Limbal-based conjunctival flap

The incision should be made as posterior as possible into the fornix to avoid restriction of aqueous drainage due to scarring ('ring of steel'). Diffuse blebs can be achieved with a LBCF with very posterior incision. The conjunctiva and Tenon's should be entered in separate layers to minimize the chance of damaging the superior rectus muscle. An incision length of at least 10 mm is needed to provide adequate exposure.

Fornix-based conjunctival flap

A conjunctival incision of ?5-10 mm is needed. A relieving incision is not required and increases tissue trauma and risk of wound leakage. The conjunctival/sub-Tenon's pocket measuring ?10-15 mm posterior and wide is constructed by careful dissection using Westcott scissors. Care is taken to accurately identify and dissect into the suprascleral sub-Tenon's plane. The essential step in this process is to identify and dissect through and posterior to the Tenon's ligamentous insertion. When dissecting over the superior rectus tendon, the conjunctiva is lifted while cutting the attachments to avoid the tendon itself (Fig. 220.4).

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FIGURE 220.4 Dissection over rectus tendon lifting conjunctiva to prevent hemorrhage.

Scleral Flap

Function of scleral flap

The main function of the scleral flap is to provide resistance to aqueous outflow and prevent hypotony. It also acts as a safety valve to minimize IOP fluctuations or spikes.

Technique of flap construction

There are several types of scleral flaps - the most common being rectangular and triangular in shape. There is no evidence that one is superior to the other. The construction of a rectangular partial-thickness scleral flap (?50% thickness) involves outlining a 3.5 ×4.5 mm flap with a blade, followed by lamellar dissection anteriorly just into clear cornea using a scleral pocket knife. Alternatively, a scleral pocket can be made after an initial incision (like a phacoemulsification pocket), before performing the two side incisions (Fig. 220.5). The side incisions are cut ?85-90% to the limbus to reduce anterior aqueous jet and encourage posterior aqueous flow, resulting in a more diffuse noncystic bleb (Fig. 220.6).

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FIGURE 220.5 Scleral pocket being dissected using pocket knife.

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FIGURE 220.6 Limited side cuts to scleral flap to encourage posterior flow and diffuse bleb.

Problems in scleral flap construction

Thin scleral flaps must be avoided because they increase the risk of flap dehiscence, formation of full-thickness scleral blowholes and cheese-wiring of the flap sutures, all of which lead to reduced flap resistance with unprotected aqueous outflow and subsequent hypotony. This is of paramount importance in eyes with low scleral rigidity (e.g., buphthalmos and myopia) and with antifibrotic use because the conjunctival resistance may not rise for several weeks or even months after surgery. If the eye has had multiple previous operations, then it is easy to buttonhole the adherent conjunctiva. Also, the limbal area may be very thin with risk of inadvertent intraocular penetration. Large aqueous veins in the area of the scleral flap should be avoided as these may subsequently act as a full-thickness blowhole.

Intraoperative Antifibrotic Use

The full details of all antiscarring agents are too extensive for this chapter and are covered elsewhere. Many of the potential agents are summarized in Table 220.2.


TABLE 220.2 -- Sequence of Events in Tissue Repair and Possible Types of Modulation After Glaucoma Filtering Surgery (Events and Agents have Overlapping Time Duration and Action)

Event

Possible modulation

Activated conjunctiva 'pre-activated' cells

Stop medical therapy (especially drops causing red eye)

Pre-operative steroids

Conjunctival/episcleral/scleral incisions

Damage to connective tissue

Minimal trauma

Less invasive surgical techniques

Release of plasma proteins and blood cells

Hemostasis (blood can reverse MMC)

Activation of clotting and complement

Agents preventing/removing fibrin, e.g., heparin, tissue plasminogen activator, hirudin

Fibrin/fibronectin/blood cell clot

Release of growth factors from blood

Antagonists to growth factor production, e.g., antibodies to growth factors humanized anti TGF-beta2 antibody (CAT 152 TrabioR) or receptors

Anti-sense oligonucleotides, ribozymes

Less specific antagonists e.g. tranilast, genistein, suramin

Aqueous released from eye

Breakdown of blood aqueous barrier

Release of growth factors into aqueous

Aqueous begins to flow through wound

Blood aqueous barrier stabilising agents e.g., steroids

Non-steroidal anti-inflammatory agents

Migration and proliferation of polymorphonuclear neutrophil cells, macrophages and lymphocytes.

Anti-inflammatory agents e.g., steroids/cyclosporine

Antimetabolites e.g., 5-FU/MMC,

Antibodies to inflammatory mediators

Angiotensin converting enzyme or chymase inhibitors

Activation, migration and proliferation of fibroblasts

Pre-operative steroids to reduce activation

Antimetabolites e.g., MMC/5-FU

Methylxanthine derivatives, Mushroom lectins

Antiproliferative gene p21(WAF-1/Cip-1)

Photodynamic therapy

Wound contraction

Anti-contraction agents e.g., colchicine, taxol lectins, MMP inhibitors

Fibroblast synthesis of tropocollagen, glycosaminoglycans and fibronectin

Interferon alpha, MMP inhibitors, fibrostatin-c

Collagen cross linking and modification

Anti-cross linking agents e.g., beta-aminopropionitrile/penicillamine

Blood vessel endothelial migration and proliferation

Inhibitors of angiogenesis e.g., fumagillin analogs, heparin analogs

Resolution of healing, apoptosis, disappearance of fibroblasts

MMC 5-FU Death receptor ligands

Stimulants of apoptosis pathways

Fibrous subconjunctival scar

Modified from Khaw et al[92]

Antifibrotic choice and treatment duration

The choice of antifibrotic agent and treatment duration should be stratified according to patient risk factors. The Moorfields more flow regimen is an example of such a model (Tables 220.3 to 220.6). The regimen uses 3 min of MMC treatment and titrates the effect of MMC by varying the MMC concentration. Intraoperative 5-FU (50 mg/mL) is used for low-risk patients. Pharmacokinetic experiments have shown a rapid uptake of 5-FU on a sponge over 3 min after which there is a plateau when relatively little effect is seen for extra application. In the period from 1 to 3 min there can be considerable variation in the dose of 5-FU delivered.


TABLE 220.3 -- Risk Factors for Failure due to Scarring after Glaucoma Filtration Surgery

Risk Factors

Risk 1-3+

Comments

Ocular

Neovascular glaucoma (active)

+ + +

Previous failed filtration surgery

+ + (+)

Previous conjunctival surgery

+ +

Uncertain

Chronic conjunctival inflammation

+ + (+)

Previous cataract extraction (conj incision)

+ + (+)

Aphakia (intracapsular extraction)

+ + +

Previous intraocular surgery

+ +

Depends on type of surgery

Uveitis (active, persistent)

+ +

A red, injected eye

+ +

Previous topical medications

+ (+)

Particularly if they cause a red eye

(beta-blockers + pilocarpine)

+ + +

(beta-blockers + pilocarpine + adrenaline)

+ (+)

New topical medications

High preoperative intraocular pressure (higher with each 10 mmHg rise)

+ (+)

Time since last surgery

+

(especially if within last 30 days)

+ + (+)

Inferiorly located trabeculectomy

+

Patient

Afro-Caribbean origin

+ +

May vary e.g., West vs East Africans

+ + (+)

+

Indian subcontinent origin

+

Hispanic origin

(+)

Japanese origin

(+)

Elderly (+) vs Young + (+) (particularly children) + +


TABLE 220.4 -- Possible Risk Factors for Antifibrotic Related Complications

Elderly patient

Primary surgery no previous medications

Poorly supportive scleral tissue prone to collapse e.g., Myopia/buphthalmos/Ehlers Danlos syndrome

Thin conjunctiva or sclera

Bleb placed in interpalpebral or inferior position


TABLE 220.5 -- Moorfields Eye Hospital (More Flow) Intra-Ooperative Single Dose Anti-Sscarring Regimen V2006 (Continuously Evolving). Lower Target Pressures Would Suggest a Stronger Agent was Required

Low Risk Patients (Nothing or Intraoperative 5-FU 50 mg/mL *)?

No risk factors

Topical medications (beta-blockers/pilocarpine)

Afro-Caribbean (Eelderly)

Youth <40 with no other risk factors

Intermediate Risk Patients (Intraoperative 5-FU 50 mg/mL * or MMC 0.2 mg/mL)?

Topical medications (adrenaline)

Previous cataract surgery without conjunctival incision (capsule intact)

Several low risk factors

Combined glaucoma filtration surgery/cataract extraction

Previous conjunctival surgery, e.g., squint surgery/detachment surgery/trabeculotomy

High Risk Patients (Intra-operative MMC 0.5 mg/mL)?

Neovascular glaucoma

Chronic persistent uveitis

Previous failed trabeculectomy/tubes

Chronic conjunctival inflammation

Multiple risk factors

Aphakic glaucoma (a tube may be more appropriate in this case)

*

Intraoperative beta-radiation 1000 cGy can also be used.

?

Post operative 5-fluorouracil injections can be given in addition to the intra-operative applications of antifibrotic.


TABLE 220.6 -- Various Intra-operative Anti-scarring Agents Applied Directly to the Bleb Site

5-FU 50 or 25 mg/mL

Beta-radiation 1000 cGy

MMC 0.2-0.5 mg/mL

Delivery

2-5 mins

20s to- 3 mins depending on output rate

2-5 min

Cost

UK£1.50 10 mL vial

Approx

UK£8 2 mg vial makes 5 mL of 0.4 mg/mL

UK£3000 for probe but lasts 10+ years

Availability

Good

Special ordering and licensing required

Good

Storage

Room temperature ready constituted

Lead shielded area

Powder stable at room temp

Unstable once reconstituted

Duration effect on fibroblast proliferation

Several weeks

Several weeks

Months/- permanent

Clinical effects several years

Cell death at higher range concentrations

Growth arrest and Cell death

Primary effect

Growth arrest

Growth arrest

Control over area treated

Moderate

Precise

Moderate

There have been reports of 5-FU given intra-operatively directly into the filtration site during surgery[93-95] However, the risk of intraocular penetration is great and commercial 5FU is alkaline with a pH of almost 9.0. Injected MMC has also been reported[80-83] but one case of combined central retinal artery and vein occlusion has been reported following MMC injection.[84] There are also cases of scleral melting and severe limbal stem-cell deficiency reported.[85] Fifty microlitres of MMC (one drop) can possibly damage the cornea.

Conjunctival/sub-Tenon's pocket

In both LBCF and FBCF, a conjunctival/sub-Tenon's pocket measuring ?10-15 ×10-15 mm is constructed by meticulous dissection with Westcott scissors to allow a large area for antifibrotic treatment. The dissection must be made into the suprascleral sub-Tenon's plane. In cases of extensive scarring or multilayered Tenon's, a Tookes knife can be used to dissect off Tenon's and expose the bare sclera.

Sub-Tenon's/subscleral flap treatment

Antifibrotic agent can be applied onto the bare sclera alone, or in combination with treatment under the scleral flap. The main concern against subscleral flap treatment was the fear of increased intraocular antifibrotic entry causing toxicity. However, there is reasonable pharmacokinetic and clinical data now to suggest that subscleral application is safe.[41] and clinical observation indicating that subscleral fibrosis occurs.

If subscleral flap treatment is planned, antifibrotic is applied after constructing the scleral flap, but before the eye is entered. If there is any problem with the scleral flap, scleral integrity or any sign of aqueous leak, the use of antifibrotics can be withheld safely.

Techniques of application

Variations in the technique used to deliver intraoperative antifibrotics may account for some of the variations in efficacy and complications seen in the literature. It is very important for individual users to maintain a consistent technique and to build up experience with one technique.

Conjunctival clamp

Special noncrushing conjunctival clamps (e.g., Duckworth-and-Kent.com T-clamp No 2-686) may be helpful. These hold back the conjunctiva and maintain the conjunctival pocket (Fig. 220.7). Clamp use may minimize antifibrotic contact with the conjunctival edge and facilitate optimal conjunctival healing to prevent postoperative wound leaks and bleb-related problems.

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FIGURE 220.7 Conjunctival T clamp for holding tissue away from antifibrotic.

Delivering the antifibrotic agent

Many methods exist for delivering antifibrotics into the sub-Tenon's pocket (e.g., sponge or filter paper). Medical grade polyvinyl alcohol (PVA) sponges are preferred to methylcellulose sponges because they maintain integrity and do not fragment.[42] In contrast, methycellulose sponges fragment relatively easily, increasing the chance of leaving residue microdebris, causing foreign body granulomas.[43]

The PVA sponges used as LASIK corneal shields can be cut in half and folded to ?5 × 3 mm before insertion into the pocket without edge contact (up to 6 pieces) (Figs 220.8 and 220.9). Alternatively a series of small 2-3 mm3 sponge can be inserted.

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FIGURE 220.8 Polyvinylalcohol sponges being folded.

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FIGURE 220.9 PVA sponge being inserted avoiding the cut edge of conjunctiva.

Antifibrotic treatment should cover the largest area possible to create a more diffuse noncystic bleb and prevent the develop-ment of a posterior limiting scar ('ring of steel'). Immediately after sponge removal (count sponges in and out), irrigation with 20 mL of BSS is performed.

Scleral Flap Sutures - Fixed, Releasable, and Adjustable

Function and types of scleral flap sutures

The function of the scleral flap sutures is to secure the scleral flap and provide adequate tension so that the flap acts as an aqueous flow restrictor. The tension provided by the flap and sutures is particularly important when antifibrotics are used as the scleral flap is the primary regulator of IOP until resistance builds up at the level of the conjunctiva/Tenon's, which may be many months after GFS. This tension is also important in eyes prone to postoperative AC shallowing, malignant glaucoma and/or hypotony. In these cases the sutures should be tied tight to provide sufficient resistance. Several types of suture can be used, including interrupted sutures which can be lasered (laser suture lysis), releasables which can be removed or a newly developed adjustable suture technique.

Placement of sutures

In a rectangular scleral flap, the initial two sutures are placed at the posterior corners of the scleral flap, using a 10-0 nylon suture. Some sutures (e.g., 10-0 Alcon) are subjectively better for use as releasable or adjustable sutures. Having placed the initial two sutures, the need for further flap sutures can be assessed by inflating the eye through the paracentesis and observing the amount of aqueous outflow. Preplacing the scleral flap sutures is technically easier on a firm globe before intraocular entry and the sutures can be tied rapidly during closure to shorten the duration of intraoperative hypotony.

Principles of scleral flap suture removal

The aim of placing and removing the scleral flap sutures is to control the extent of aqueous filtration (and IOP) through the scleral flap. In general, suture removal/lysis is avoided in the early postoperative period to prevent inadequate flap resistance and aqueous overdrainage leading to hypotony. This is a particular problem with adjuvant antifibrotic therapy. However, early suture removal (leading to an early high aqueous flow) may be required in some circumstances including in young patients, African-Caribbean patients and patients with severe secondary glaucoma where early sub-Tenon's fibrosis with irreversible suboptimal bleb architecture can occur.

Fixed sutures and laser suture lysis

Laser suture lysis (LSL) was introduced in 1983 by Lieberman using an argon laser to lyse excessively tightened scleral flap sutures after trabeculectomy.[44] Since then, there has been much interest in LSL including the use of different lasers and power settings,[45-49] and the introduction of different types of suture lysis device/lenses.[50]

Savage et al studied LSL in nonaugmented trabeculectomy and showed that LSL can provide serial lowering of IOP after initial tight closure of the scleral flap. The most substantial IOP drop after LSL occurred during the first 2 weeks and was usually ineffective after the fourth postoperative week. LSL was however associated with significant complications including hypotony with shallow AC (16.7%), progressive significant cataract (16.7%), conjunctival perforation (4.8%) and conjunctival wound leak (7.1%).[51] Melamed et al[52] also found LSL to be effective and with similar complications. LSL was reported to have no effect on the long-term success rate of trabeculectomy in one study, but the study was confounded by the use of postoperative 5-FU.[53]

It was postulated that the delay of healing caused by MMC in trabeculectomy would extend the clinically effective window period for LSL. Many studies demonstrated that LSL was effective beyond 2 months in some cases.[54,55] However, post-LSL hypotony remained significant and led to decreased vision. The safety of LSL was investigated in a large study by Macken et al[56] and found significant flat AC with iridocorneal touch (13.1%) and conjunctival leaks (9%). Kapetansky[57] minimized post-LSL hypotony by delaying LSL after trabeculectomy with MMC by using digital massage to gauge the degree of healing. LSL after the second postoperative month was suggested to prevent LSL-induced hypotony without adversely affecting the final IOP. In contrast, Ralli et al[58] reported an increase in GFS failures in eyes that underwent LSL more than 10 days postoperatively. In eyes that had LSL within 10 days after trabeculectomy with MMC, the long-term IOP control was no different to the non-LSL group. One of the major concerns with LSL has been the effect of laser on the conjunctiva overlying the scleral sutures. Cases of conjunctival perforation resulting in persistent leak have been described.[51,59]

Releasable sutures

Several years after the introduction of LSL, interest in releasable scleral flap sutures increased because of the technical and logistical difficulties of performing LSL.[60] In LSL, the scleral flap sutures can be obscured by subconjunctival hemorrhages, thickened Tenon's capsule or fibrosis.[61] The idea of releasable scleral flap sutures originated from Shaffer et al in 1971 where externalized mattress sutures were used to prevent shallow AC following thermal sclerostomies.[62]

The interest in releasable sutures was revived in the late 1980s when Shin[63] and Cohen and Osher[64] described their releasable suture techniques. In the 1990s, many different methods were described,[65-70] but the method described by Cohen and Osher with a trimmed suture end on peripheral cornea, remained the most popular. Cases of endophthalmitis have been reported following trabeculectomy with MMC using the technique possibly due to the exposed suture end acting as a nidus for infection.[71,72]

Later modifications aimed to bury the externalized suture leaving no exposed free ends.[67,70,73] The technique described in this chapter was reported in 1996,[74] which eliminates the free suture end, and also leaves all sutures buried but still accessible by the use of corneal grooves leaving no exposed portion.

The use of releasable sutures has been found to significantly reduce postoperative hypotony and shallow AC compared to permanent sutures. Reported complications include superior corneal epithelial abrasions and suture breakage on removal. There is no clear evidence that the use of releasable sutures improves GFS success.[60,70]

Technique of releasable suture

Two reverse-stepped clear corneal grooves are made to allow preplacement of 2 releasable 10-0 nylon sutures in the scleral flap before blade entry into the anterior chamber. The suture is placed by passing the needle from just behind the limbus beside the scleral flap to emerge from the corneal groove. The needle is passed back into the corneal groove, through the partial-thickness scleral flap and emerges from the posterior third of the flap. The needle is then passed full-thickness through the corner of the scleral flap into the adjacent scleral bed at an angle of 45°, leaving a loop to be secured with a single triple-throw loop.

Adjustable sutures

A recent development in scleral flap suture technique was an adjustable suture which allows trans-conjunctival adjustment of tension postoperatively using specially designed forceps with smooth edges (Duckworth-and-Kent.com, Khaw adjustable suture forceps No 2-502) (Fig. 220.10). The adjustable suture system allows a gradual titration of IOP - more gradual than that seen with suture removal or massage[75,76] (Fig. 220.11).

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FIGURE 220.10 Adjustable suture forceps with special fine smooth tips for transconjunctival suture adjustment without tearing conjunctiva.

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FIGURE 220.11 Transconjunctival loosening of adjustable sutures without sudden fall in intraocular pressure.

In summary, Changes in area of antifibrotic treatment, conjunctival and scleral flap construction, and scleral flap sutures have led to a dramatic reduction of both short- and long-term complications (Fig. 220.12). This has led to a reduction in cystic areas within the bleb from 90% to 29% as well as the rate for blebitis and endophthalmitis.[40] Falls in complication rate have also been seen in the USA in lower risk populations from ?6% to 0.5% to date (P Palmberg, personal communication) If these figures were extrapolated to an approximate figure of 50 000 trabeculectomies with antifibrotic per year in the United States it is possible that bleb related complications could be avoided in many thousands of patients.

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FIGURE 220.12 Showing diffuse bleb in patient's right eye using large area of treatment vs a smaller area of treatment with mitomycin-c.

Paracentesis

Functions of paracentesis

A paracentesis allows fine control of the AC in several intra- and postoperative situations:

1.

To set the opening pressure of the scleral flap with precision after tying the flap sutures (IOP titration) - BSS is injected via the paracentesis while observing the emergence of fluid from the scleral flap.

2.

Reformation (or decompression) of AC both intra and postoperatively - BSS and/or viscoelastic can be used.

3.

An infusion can be placed to maintain a continuous intraocular pressure particularly in high-risk patients

4.

Control and washout of AC hemorrhage - Viscoelastic can be injected to provide tamponade. air injection and BSS for washout.

An oblique paracentesis placed in the inferior cornea parallel to the limbus is self-sealing and minimizes the risk of lens damage. It is much safer if the anterior chamber is shallow.

Anterior Segment Infusion

An anterior segment infusion (e.g., Lewicky, BD Visitec NJ) on a three-way tap can be used through the paracentesis to offer another level of IOP and AC control (Fig. 220.13). The IOP and rigidity of the globe is maintained intraoperatively particularly in eyes with an increased risk of rapid choroidal effusion and hemorrhage (e.g., infants, high myopes, nonophthalmos, buphthalmos and Sturge-Weber syndrome). IOP can be titrated using the infusion height to increase the accuracy of scleral flap closure and significantly reduce postoperative hypotony.

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FIGURE 220.13 Anterior segment infusion to maintain intraocular pressure and gauge opening pressure of sclerostomy. Inserted with an oblique paracentesis in a phakic eye to minimize any risk to lens.

Sclerostomy

The sclerostomy can be created in various ways. It can be manually cut and removed with appropriate blade and scissors, or alternatively a special punch can be used.

Placement of initial incision

With the development of precision instrumentation, it is now possible to create an anterior corneoscleral entry into the AC. An anterior incision reduces the risk of iris incarceration and bleeding from the iris root or ciliary body.

Punch sclerostomy

A punch sclerostomy is the method of choice, and many punches are available. A sclerostomy measuring 0.5-2 ×0.5-1.5 mm is adequate and provides optimum outflow control whilst minimizing astigmatism and anterior aqueous flow.[77] Blade entry into the AC is performed anteriorly through clear cornea beneath the scleral flap. The punch is inserted to engage the full-thickness of limbus. The punch should be aligned perpendicularly to ensure a clean nonshelved sclerostomy (Fig. 220.14).

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FIGURE 220.14 Small 0.5 mm titanium scleral punch to maximize flow control.

Manual block removal

If a blade and scissors are used it is difficult to cut a sclerostomy much smaller than 3 × 1.5 mm. The scleral flap is gently lifted with care not to cause a buttonhole. The block is outlined to at least 90% depth before AC entry through the anterior edge. The rest of the block is dissected posteriorly to full-depth, using a blade or Vannas scissors to cut the base. Gentle traction is applied to the block during dissection preventing damage to the iris and underlying structures. Problems with manual block removal include difficulty in cutting/dissecting anteriorly and the creation of a larger hole causing shallow AC and hypotony.

Peripheral Iridectomy

A peripheral iridectomy (PI) is performed through the sclerostomy. The presence of a PI prevents iris incarceration and relieves pupillary block in some cases. The PI should be made relatively broad at the base and, short in length to reduce the size of iris defect, minimizing glare and monocular diplopia. Cutting the PI with scissors held parallel to the sclera facilitates this. The iris can be made to present through the sclerostomy without intraocular manipulation using an infusion, reducing iris trauma and the need for an assistant. (Fig. 220.15)

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FIGURE 220.15 Iris presenting through small sclerostomy with gentle pressure on back edge when infusion used. No intraocular entry necessary.

IOP Titration

After PI, preplaced scleral flap sutures can be tied quickly to minimize the duration of hypotony. IOP titration is a key step in GFS where the opening pressure of the scleral flap is precisely set with the injection of BSS through the paracentesis or using an AC infusion. The point where aqueous emerges from the scleral flap is the opening pressure. Scleral flap sutures are tighted/loosened accordingly and extra sutures placed as needed.

Closure of Conjunctiva and Tenon's

Prevention of wound leaks are of paramount importance in FBCF surgery. Wound leaks lead to flattened bleb morphology and hypotony, increasing the risk of GFS failure. Therefore great attention has been focused on reproducible water-tight closure technique. Traditional closure used single interrupted suture at the ends of conjunctival incision, newer techniques include the use of lateral purse-string sutures, interrupted horizontal mattress sutures[78] or a suture with corneal grooves.[79] 'Corneal groove closure' involves creating a series of corneal grooves through which conjunctival sutures with buried knots can be placed. This technique has virtually eliminated central conjunctival/Tenon's retraction, wound leaks and suture discomfort (Figs 220.16 and 220.17).

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FIGURE 220.16 Corneal groove creation (five grooves) for closure of fornix based conjunctival flap to minimize leakage and suture discomfort.

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FIGURE 220.17 Lateral purse string - entry via cornea and out via limbus, purse string, back in at limbus and out through corneal grove and tie in grove. Repeated procedure temporally and then 1-3 central mattress sutures.

For a LBCF, an absorbable suture (e.g., vicryl) is usually used for closure using interrupted or continuous suturing. Absorbable suture is preferred for patient comfort and ease of management despite the theoretical increase in inflammation. A round-bodied rather than a spatulate needle is used (especially with MMC) to minimize the risk of conjunctival tears, cheese-wiring and leaks. Suture bites should include both the conjunctiva and Tenon's in single-layer closure to ensure a watertight wound. Following conjunctival closure, BSS is injected via the paracentesis to ensure patency of the scleral flap (observing the drainage bleb) and watertight closure.

Medications at End of Procedure

Traditionally, a subconjunctival injection containing steroid and antibiotic is given 180 degrees away from the trabeculectomy site to prevent intraocular entry. Mydriatics/cycloplegics such as atropine 1% may be used although with advanced techniques this is now less common. Advantages include relaxation of the ciliary muscle and pain relief, reduction of AC shallowing and malignant glaucoma (especially in short axial length eyes), stabilization of the blood aqueous barrier (Atropine mainly) and prevention of central posterior synechiae. Disadvantages include a dilated pupil which may increase lens-corneal touch in shallow AC, and loss of accommodation causing blurred vision.

Ocular Dressing

At the end of GFS, the eye is lubricated with antibiotic ointment before lid closure. The placement of a paraffin gauze dressing (Jelonet), eye pad followed by shield ensure closure and offers extra protection. The aim is to achieve good lid closure and prevent any corneal epithelial breakdown, which can be slow to heal postoperatively, causing subsequent postoperative treatment (steroids) and bleb manipulation delays.

POSTOPERATIVE MEDICATIONS

Topical Steroids

Early restoration of the blood-aqueous-barrier and suppression of wound healing response are important in the early to intermediate postoperative period. Steroids (prednisolone acetate 1%) are prescribed 2 hourly for the first 2 weeks with subsequent dosing adjusted according to bleb morphology. Most patients receive a reducing dose of topical steroids for ?8 weeks postoperatively.

Topical Antibiotics

Patients usually receive antibiotics for ?4 weeks postoperatively.

Topical Mydriatic/Cycloplegic Agents

The main purpose of using atropine 1% is to prevent postoperative AC shallowing AC and the risk of malignant glaucoma, especially in eyes with short axial lengths or chronic angle closure.

Topical NonSteroidal Antiinflammatory Drugs

These may be useful in selected patients at high risk of failure but their efficacy is not proven.

Oral or Intravenous Steroids

Systemic steroids are not used routinely due to their potentially dangerous side-effects. However, in severe uveitic glaucoma, the benefits of use may outweigh the risks. Systemic steroids use should be started in the preoperative period with communication/cooperation between the surgeon and the patient's family doctor and/or physician.

BLEB MANIPULATION TECHNIQUES

Bleb manipulation techniques enable the surgeon to alter aqueous outflow dynamics and modulate the healing response.

Bleb Massage

It is essential to establish the sub-Tenon's aqueous lake early in the postoperative course. A flat bleb may result from tight scleral flap sutures and digital pressure through the upper lid is exerted as posterior as possible to the scleral flap under direct slit-lamp visualization until a good bleb forms. This can be repeated several times over the first few weeks. The absence of a wound leak is a prerequisite to successful bleb massage and it is essential to avoid an iatrogenic wound leak which delays further bleb manipulation.

Scleral Flap Suture Manipulation

If bleb massage only produces a transient effect on aqueous outflow, one or more of the releasable scleral flap sutures can be removed. Alternatively, LSL may be performed or adjustable sutures loosened. Incorrect timing of suture removal/lysis may result in hypotony (performed too early) or permanent subconjunctival fibrosis and GFS failure (performed too late). One or more sutures are sequentially removed/lysed between 1 and 4 weeks postoperatively. Exact timing is influenced by individual characteristics of the eye: removal/lysis is performed earlier in those at very high risk of GFS failure and later in eyes prone to hypotony.

Adjuvant Subconjunctival 5-Fluorouracil

Postoperative injections of 5-FU can be used both in nonaugmented or augmented trabeculectomy. 5FU was originally used as a planned regimen following GFS, but with the advent of intraoperative antifibrotics, subconjunctival 5-FU injections are now used according to the postoperative clinical situation. Subconjunctival MMC injections have also been used,[80-83] but with significant complications,[84,85]and are not recommended for routine use.

Subconjunctival 5-FU is usually given after the first postoperative week and for up to several months to modulate wound healing. 5-FU inhibits fibrosis in the Tenon's layer rather than influencing scleral flap resistance. The successful use of 5-FU depends on the presence of a sub-Tenon's aqueous lake - it is unlikely to be helpful in flat blebs.

5-FU should be given as soon as possible after recognition of early bleb failure. Signs of impending bleb failure include:

1.

Increased bleb vascularity

2.

Thickening of conjunctiva and Tenon's capsule

3.

Reduction in bleb size and height

4.

Reduction of conjunctival microcysts

5.

Progressive elevation of the IOP

Prospective evaluation of the blebs using the Moorfields bleb classification showed that prolonged increased vascularity for 6 weeks was associated with a 6 fold increase in bleb failure (Fig. 220.18).

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FIGURE 220.18 Severely inflamed and encapsulated bleb - chronic severe postoperative inflammation is associated with a much higher failure rate.

Clinical situations for 5-FU use

5-FU can be used alone or as adjuvant therapy in several scenarios:

1.

As a planned postoperative regimen after GFS in patients at risk of GFS failure or requiring a low IOP.

2.

In a patient showing signs of scarring and imminent bleb failure after GFS.

3.

As adjuvant therapy following bleb needling revision.

4.

To prevent failure of an existing bleb after a healing stimulus e.g., cataract extraction.

5.

Late 5-FU injections may be given up to several months after GFS for persistent healing response and rising IOP.

Technique

1.

Subconjunctival 5-FU injection is performed under topical anesthesia with a speculum to improve access. It may useful to blanch the conjunctiva with phenylephrine 2.5% or apraclonidine 1% to prevent subconjunctival hemorrhage.

2.

A small-gauge needle (e.g., insulin syringe with 27 gauge needle) is used to inject 5 mg of 5-FU (0.1 mLs of 50 mg/mL or 0.2 mLs of 25 mg/mL solution) either 90 degrees from the bleb or deep in the superior fornix. The use of a small needle minimizes reflux of 5-FU into the tear film. Deep placement of needle must be avoided to prevent direct intraocular entry.

3.

5-FU should be injected slowly under direct visualization. The injection bleb should not cross into the drainage area. This is important in a soft eye due to the increased risk of intraocular tracking.

4.

The needle should be left in place for few seconds after injection to facilitate sealing of the entry site and reduce 5-FU reflux.

5.

Remnant 5-FU in the tear film should be irrigated with BSS to prevent corneal complications. A fine white precipitate in the tear film indicating residual 5-FU can be detected when topical amethocaine is used.

6.

Subconjunctival Healon GV, acting as a 'viscoelastic wall', can be used before 5-FU injection to prevents leakage back into the tear film therefore enhancing the effect of the 5-FU (Fig. 220.19).

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FIGURE 220.19 Viscoelastic wall preventing 5-FU re-entry into the tear film and the formation of a 5-FU lake.

BLEB NEEDLING REVISION

This technique aims to increase the size of the sub-Tenon's aqueous lake without causing overdrainage and hypotony. This is achieved by puncturing and/or loosening scar tissue in the region of the filtration bleb. Bleb needling revision (BNR) is used when bleb massage and/or scleral flap suture removal/lysis fails to significantly increase sub-Tenon's aqueous flow (extensive sub-Tenon's fibrosis or bleb encapsulation) (Fig. 220.20). BNR can also be performed proactively for patients exhibiting a suboptimal bleb morphology before significant scarring develops.

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FIGURE 220.20 Severely inflamed and encapsulted bleb.

There are 2 types of BNR, each aimed at addressing the site of increased resistance to aqueous out flow:

1.

Sub-Tenon's needling

2.

Subscleral flap needling

Sub-Tenon's Needling

BNR is performed under topical anesthesia either at the slit-lamp or in the operating theatre. The patient is asked to look down using an assistant or speculum to retract the upper lid. Bleb vascularity is reduced with topical apraclonidine 1% or phenylephrine 2.5%. The bleb is approached with a 29G needle via a very posterior superior fornix entry. Multiple stabs toward the scleral flap are made until a clear increase in bleb size is achieved. Gentle circumferential sweeps can also be used but may increase the risk of hemorrhage. Excessive needling should be avoided due to the risk of hypotony and the associated complications such as suprachoroidal hemorrhage. Malignant glaucoma has been reported after needling.[86] The act of BNR may reactivate the wound healing process, and subconjunctival injections of 5-FU (5 mg) and steroid (betamethasone) are given at 2 separate sites 90 degrees away from the bleb at the end of needling. Postoperatively, topical steroids and antibiotics are given.

SubScleral Flap Needling

Success of BNR is largely dependent on preexisting bleb morphology: a favorable outcome is more likely for elevated encapsulated blebs than flat blebs with extensive subconjunctival scarring. Early postoperative subscleral flap needling may be appropriate in primary GFS failure if sub-Tenon's needling fails. Fortunately, this scenario is less common as subscleral flap needling is a high-risk procedure and direct visualization of the needle tip may not be possible. Subscleral flap needling requires a high degree of expertise.

COMPLICATIONS OF TRABECULECTOMY

One must be prepared to encounter unexpected problems. Not all complications GFS can be avoided, but most can be anticipated and prevented.

INTRAOPERATIVE COMPLICATIONS

Conjunctival Tear

Conjunctival tears can be a serious problem especially with adjuvant antifibrotic. They most commonly occur during the peritomy and sub-Tenon's dissection, especially in eyes with multiple previous surgery and adhesions.

Prevention

The preoperative use of topical apraclonidine 1% or adrenaline significantly reduces tissue vascularity and bleeding, improving visualization and control of the operative field. The handling of conjunctiva should be minimized. With thin tissues, BSS should be injected under the conjunctiva/Tenon's to make them thicker and easier to handle (stromal hydration). This will also demarcate scarred tissue and open up tissue planes. During conjunctival/sub-Tenon's pocket construction, slow blunt dissection using very small cuts to divide adhesions and continuous reassessment of the plane minimizes the chance of a tear.

Management

If a conjunctival tear occurs without adjuvant antifibrotic, it can be repaired by a simple purse-string vicryl suture on a vascular needle. If antifibrotics (especially MMC) are used, a patch graft using tissue without antifibrotic contact may be needed. This can be done by dissecting an attached flap of Tenon's capsule distant to the treatment area, and then rotating it underneath the conjunctiva to be sewn as a living patch underneath the tear.

Conjunctival, Scleral, and Iris Bleeding

Bleeding must be minimized in GFS as blood is a potent stimulus for fibrosis. When bleeding occurs, prompt hemostatic measures should be employed.

Prevention

The prevention of intraoperative bleeding starts well before GFS with the discontinuation of aspirin, anticoagulants or herbal remedies (e.g., Gingko Biloba) if medically feasible. The use of topical apraclonidine 1% or adrenaline at time of surgery effectively reduces tissue vascularity. Handling of tissues (whether extraocular or intraocular) should be minimized.

Management

Gentle wet-field diathermy (either bipolar or unipolar) can be used to control bleeding. The lowest possible power setting must be used to prevent tissue shrinkage. When rapid bleeding occurs from the PI, the preplaced scleral flap sutures are tied and the IOP raised via the paracentesis to provide tamponade. Bleeding usually stops quickly. Then the scleral flap can be loosened to allow gentle irrigation and AC washout. Larger hemorrhages may be controlled by raising the IOP with viscoelastic or AC infusion.

Scleral Flap Damage

Damage to the scleral flap including tearing or buttonhole can occur during flap construction (before sclerostomy) or after sclerostomy.

Prevention

Scleral flap damage is prevented by avoiding a thin flap which predisposes to cheese-wiring and tearing, and reducing the amount of scleral flap manipulation.

Management

If the scleral flap is damaged during construction/dissection, further surgery should continue at a new site with undamaged sclera. After sclerostomy creation, minor flap damage may be repaired with a 10-0 nylon suture. In severe damage where the sclerostomy cannot be secured, an autologous or donor scleral patch, or processed pericardium may be sewn onto the operation site to regain globe integrity.

Suprachoroidal Hemorrhage

Suprachoroidal hemorrhage (SCH) may occur in any eye where the AC is suddenly decompressed and shallowed (e.g., during sclerostomy creation).

Prevention

The principle of preventing on-table SCH rests with the maintenance of IOP, whilst preventing sudden IOP reductions. The preoperative identification of high-risk eyes (e.g., young patient, large eyes, small eyes, Sturge-Weber syndrome) combined with modifications in surgical strategy are the critical steps in preventing this potentially blinding complication. Patients shall stop medications which predispose to bleeding. Strategies to maintain intraoperative IOP include preplaced scleral flap sutures, injection of viscoelastic into AC before intraocular entry and the use of an AC infusion during GFS. The use of a sclerostomy punch as opposed to 'block excision' also offers improved IOP control. Choroidal vasoconstriction induced by hyperventilation under GA may also be a helpful measure. In nanophthalmic eyes, scleral decompression may be required before intraocular entry. Similarly, postoperative suprachoroidal hemorrhage is prevented by prevention of hypotony (e.g., use of viscoelastic or C3F8 in aphakic eyes) and avoidance of valsalva maneuvers.

Management

If SCH is suspected, all wounds should be closed rapidly to ensure ocular integrity. The posterior segment is assessed to confirm the diagnosis. If the SCH is peripheral and not affecting the macula, then a conservative approach is recommended. If the SCH is extensive then drainage can be performed before the blood clots through one or more sclerostomies.

Decompression Retinopathy

Retinal hemorrhages have been reported after rapid IOP reductions during GFS.[87,88] A sudden and substantial IOP drop have been hypothesized to cause retinal vascular deregulation and forward movement of the lamina cribrosa leading to blockage of axonal transport and compression of central venous vein.[89,90]

Decompression retinopathy is prevented by gradual reductions of IOP using the paracentesis before intraocular entry and a conservative management is recommended. The use of GA allows the IOP to be slowly reduced before the eye is entered.

Vitreous Loss

Vitreous loss during trabeculectomy occurs when the lens/zonule complex is inadvertently damaged during the PI, which is performed too posteriorly. The presence of vitreous in the AC will lead to potential blockage of the ostium and can increase the risk of GFS failure.

Prevention

1.

Create sclerostomy anteriorly

2.

Avoid very basal PIs

3.

Note iridolenticular instability preoperatively and consider alternative procedure (e.g., tube surgery) if high risk of vitreous prolapse

Management

1.

Anterior vitrectomy

2.

Postoperative subconjunctival 5FU

Postoperative complications

'Wipe-Out' of Visual Field

This is commonly thought to occur more frequently in patients with advanced field loss, particularly if the field loss is within 10 degrees of fixation, although large scale studies to not provide good supportive evidence.

Prevention

It may be useful to check the IOP a few hours after GFS to detect and treat any IOP spike. Pre- and postoperative hypotony and systemic hypotension, all of which may compromise an already damaged optic nerve should be avoided. GFS under GA may avoid the IOP rise associated with some LA techniques.

Suprachoroidal Hemorrhage

Postoperative SCH is prevented by the prevention of hypotony. SCH occurs more frequently with valsalva maneuver, eye rubbing, forceful coughing, bending down and involuntary blepharospasm.

Infections

Blebitis and endophthalmitis are potentially blinding emergencies. Patients should seek ophthalmological attention immediately if they develop a purulent discharge.

Prevention of early infection

1.

Identification of high-risk patients (e.g., blepharitis) and manage preoperatively.

2.

Use of povidone-iodine to prepare the skin, lids, lashes and conjunctival sac.

3.

Minimize lashes in the operative field

4.

Bury all sutures including releasable sutures.

5.

Patient education regarding the importance of hand washing and avoidance of contact with infected wounds.

Prevention of late infection

Late infections are prevented by avoiding blebs with poor/cystic morphology:

1.

Avoid excessive treatment with antifibrotic agents.

2.

Avoid thin scleral flaps, which predispose to blowholes and necrosis (especially with MMC).

3.

Use large areas of antifibrotic treatment and agents such as beta-irradiation to produce more diffuse noncystic blebs.

4.

Position bleb under the upper lid in position with maximal cover. The blebitis/scleritis and infection rate may be 5-10 times higher with blebs unprotected by the upper lid. Carry out tube surgery or other therapies instead of inferiorly placed blebs.

Management

Blebitis is treated by topical and systemic antibiotic after obtaining swabs. With any suspicion of endophthalmitis (e.g., vitreous cells), conjunctival swabs, aqueous and vitreous taps must be performed. Intravitreal antibiotics should be given even with negative cultures. A vitrectomy should be considered to debulk the infective agent and toxins with marked vitreous activity. Hemophilus and streptococcus are the commonest organisms causing bleb related endophthalmitis, and should be covered by the antibiotic regimen.

Complications with Low IOP

Wound leak

Conjunctival wound leaks must be avoided as they make further bleb manipulation difficult. Aqueous leakage decreases bleb height and leads to increased subconjunctival fibrosis and failure.

Prevention

1.

Smaller conjunctival incision (in both FBCF and LBCF)

2.

Prevention of conjunctival tear and buttonholes by minimizing tissue handling and the use of round vascular (BV) needle.

3.

In FBCFs, meticulous conjunctival wound closure.

4.

In LBCFs, place conjunctival incision as posteriorly as possible.

5.

Careful conjunctival edge protection during antifibrotic application and the use of a noncrushing clamp.

Management

Small wound leaks are often self-limiting especially in the presence of an elevated bleb with good posterior aqueous drainage. For persistent leaks, treatment options include reduction or discontinuation of topical steroids, use of a pressure dressing, bandage contact lens or Simmonds' shell, and conjunctival resuturing. Significant leaks with hypotony and choroidal effusions are best managed by wound resuturing.

Bleb overdrainage

The use of antifibrotics (especially MMC) has increased the incidence of hypotony due to overdrainage. Most hypotony (IOP < 6 mmHg) in the early postoperative period settles without intervention. The hypotony becomes clinically significant (Clinically Significant Early Hypotony, CSEH) when it persists with shallow AC, choroidal detachement or hypotonous maculopathy - surgical intervention is then indicated.

Prevention

Hypotony due to aqueous overdrainage is commonly seen in eyes with low scleral rigidity (e.g., young patient, myopia, collagen abnormality). Preventative strategies include:

1.

Tight scleral flap closure with extra sutures as indicated by IOP titration

2.

Avoid small or thin scleral flaps which may not provide adequate resistance to aqueous outflow

3.

Do not release/lyse scleral flap sutures too early. With MMC, suture removal may result in hypotony even months after GFS. It is preferable to perform bleb massage rather than releasable suture removal.

4.

Avoid high dose MMC in patients prone to postoperative hypotony

Management

CSEH is managed by the injection of viscoelastic to the AC until significant sub-Tenon's and/or scleral flap resistance build up. Patients at risk of CSEH are often predisposed to wound leaks, therefore conjunctival wound leaks should also be resutured when present.

Choroidal effusion

Choroidal effusions are common in hypotonous eyes following GFS. The collection of fluid (high protein content) in the suprachoroidal space is produced by transudation from leaking capillaries in the choriocapillaris.

Prevention

The measures to prevent choroidal effusion are the same as that for hypotony due to overdrainage.

Management

Conservative treatment is the recommended with mydriatic/cycloplegic agents and frequent topical steroids. Surgical intervention may rarely be needed in lens-corneal touch and apposition of the effusions ('kissing choroidals'). Other causes of choroidal effusion should be considered when the IOP is normal (e.g., scleritis, low serum protein levels and nanophthalmos).

Ciliary body shutdown

Patients with uveitis are at risk of developing ciliary body shutdown, which can be prevented by preoperative optimization of intraocular inflammation. The management involves frequent topical and/or systemic steroids.

Late bleb leak

Bleb leaks can occur months or years after GFS, especially with adjuvant antifibrotics such as MMC. The leak may be focal or diffuse with 'sweating' areas (Fig. 220.21).

Click to view full size figure

FIGURE 220.21 Bleb oozing aqueous secondary to cystic change.

Prevention

Late bleb leaks are prevented by avoiding thin scleral flaps to reduce the formation of blowholes and anterior aqueous flow which increase the risk of cystic blebs. Also, the use of antifibrotics must be titrated according to patient risk factors to avoid excessive treatment.

Management

The decision to treat is multifactorial: patient factors including symptoms, size of the leak, bleb morphology, risk factors for infection, the presence of hypotony and hypotony associated complications must all be considered. Small leaks may settle spontaneously. Treatment options include:

1.

Large diameter contact lenses.

2.

Bleb compression sutures - 9/0 nylon sutures are sewn across the bleb compressing the leak site. This can be combined with autologous blood injection. While the sutures stay in situ the patient should continue on prophylactic antibiotics.

3.

Laser treatment to the deep scleral flap.

4.

Trichloracetic acid painted on bleb.

5.

Quilting sutures to limit bleb overdrainage.

6.

Autologous blood injection(1 ?2 mL) - This can be given both into and around the bleb. The IOP may rise immediately after injection due to the clotted blood obstructing outflow. However, the pressure will fall when the fibrinolytic system is activated. The injected blood may enter the AC to cause a hyphema, or the vitreous cavity resulting in a vitreous hemorrhage (particularly in pseudo or aphakic eyes). The use of concurrent viscoelastic in the AC to raise IOP prevents blood entry, however, this may result in a large, persistent IOP rise and is not advised.

7.

Bleb revision with donor lamellar scleral graft - This is the most effective treatment where the cystic avascular area is resected and viable vascularized conjunctiva is brought over. A donor lamellar scleral patch is sewn on top of the previous scleral flap where a full thickness blowhole is often found. Cystic bleb may recur without a scleral patch graft. (Fig. 220.14) The technique is very effective in stopping leaks, but may cause increased IOP.

8.

Cataract surgery may produce an inflammatory reaction needed to stimulate wound healing, restoring the bleb to an acceptable condition. It is important to remember that biometry accuracy is more variable in a hypotonous eye.

Complications with Raised IOP

Raised IOP after GFS is almost always due to inadequate aqueous outflow. Management depends on the site of obstruction - obstructions can occur simultaneously at several sites.

Posterior diversion of aqueous (Malignant glaucoma)

In malignant glaucoma the aqueous is directed posteriorly into the vitreous cavity with restriction of anterior flow by the anterior hyaloid face. Patients usually present with shallow AC and raised IOP several days after GFS. Anteriorly rotated ciliary processes have been observed to press against the lens equator and prevent anterior aqueous flow. The anterior hyaloid may be abnormally positioned, plugging spaces between ciliary processes. An acute pupil block or SCH can sometimes give a similar picture.

Prevention

Eyes with reduced axial length must be identified preoperatively. In nanophthalmos, prophylactic sclerotomies may be required. Aqueous overdrainage must be avoided in the early postoperative period by having a high scleral flap resistance - scleral flap sutures are removed later when needed. Topical atropine at the end of GFS and postoperatively is useful in preventing malignant glaucoma.

In high-risk eyes with cataract, a combined GFS and cataract procedure may debulk lens volume. A rigid one piece implant may prevent a flat AC. The capsulorrhexis should be kept relatively small to prevent lens implant/pupil capture if the AC shallows. If malignant glaucoma develops, the management is easier in a pseudophakic eye.

Management

The initial management of malignant glaucoma involves the use of mydriatic/cycloplegic agents (e.g., atropine and phenylephrine) and medications to lower IOP. When medical treatment is unsuccessful, laser (Nd:YAG) and/or surgical interventions are used. In most cases, the creation of a new aqueous drainage channel connecting the posterior and anterior segments by disrupting the peripheral anterior hyaloid face is needed. Disruption of the central hyaloid often fails to produce an adequate pathway for fluid movement and disruption should be carried out to the periphery of the capsule.

In phakic eyes, the use of Nd:YAG laser to remove the anterior hyaloid face carries a high risk of lenticular damage. A patent PI, good visualization and precise focusing are crucial. The AC will start to deepen as soon as the anterior hyaloid face is disrupted. In the presence of significant cataract, a sequence using limited core vitrectomy, phacoemulsification with lens implant, followed by residual vitrectomy with hyaloido-zonulectomy via a posterior approach through the preexisting PI (Vitrectomy-Phacoemulsification-Vitrectomy - VPV) may be utilized to create a definitive communication for aqueous flow between the posterior and anterior segments.[91]

In pseudophakic eyes, Nd:YAG laser or surgery is used to create a passage through tissues between the PI and anterior hyaloid face, including the lens capsule and any cortical lens remnants.

Pupil block

Pupil block may occur after GFS when the peripheral iridectomy becomes nonpatent (either inadequately performed or obstructed) with an occluded pupil margin (e.g., by fibrin, blood, vitreous or anterior movement of iris-lens diaphragm). The AC may become shallow with iris bombe. Management of pupil block includes medical treatment to lower IOP, Nd:YAG laser peripheral iridotomy, pupil dilatation to break any posterior synechiae and topical steroids to reduce inflammatory exudates.

Fistula blockage

Fistula obstruction is the most common cause of raised IOP in the first 1-2 weeks. Causes external to sclerostomy include tight scleral flap sutures and fibrin/blood at the level of the flap and subconjunctival space. Gonioscopy will identify obstruction at the internal aspect of the sclerostomy including plugging by iris, ciliary processes, vitreous or blood, or inadequately punched/excised corneoscleral block.

Prevention

1.

Ensure an adequate sclerostomy is performed.

2.

Avoid a posterior sclerostomy which increases the risk of obstruction by ciliary body, blood or vitreous.

3.

Use a paracentesis to check the patency and opening pressure of the scleral flap intraoperatively.

Management

1.

Gentle bleb massage may loosen any adhesions and restart aqueous flow. This may also reduce internal sclerostomy blockage. Focal pressure applied to the posterior lip of the flap (with a sterile plastic ointment applicator) is more effective than diffuse digital massage through the lids. This maneuver can also loosen the releasable suture and reduce the scleral flap opening pressure. One problem with releasable suture removal or LSL is the sudden reduction of resistance provided by the scleral flap, which can lead to overdrainage and hypotony. The patient should be re-examined ?30 min after massage to ensure that the IOP reduction is not transient.

2.

If massage fails to establish adequate aqueous drainage, releasable suture removal, LSL or transconjunctival suture adjustment may be required.

3.

Application of argon or Nd:YAG laser to the internal aspect of the sclerostomy can remove any tissue blockage.

Subconjunctival/Tenon's fibrosis

Previously functioning blebs may become encapsulated after GFS due to fibrosis. These blebs appear elevated, tense and often dome-shaped. (Fig. 220.21 Severely encysted bleb) There is fibrosis and sometimes fibrin within Tenon's capsule, particularly around the edge of the cyst. Patients previously using topical sympathomimetic agents may have higher risk of bleb encapsulation.

Subconjunctival fibrosis is prevented by adjuvant antifibrotics and postoperative topical steroids. The management includes subconjunctival 5-FU and BNR.

Cataract Formation

Cataract formation/progression may occur due lens-corneal touch, lens trauma, inflammation, hypotony and the use of intraoperative MMC. Cataract progression is reduced by avoiding postoperative hypotony and a flat AC. Use of an oblique paracentesis minimizes the risk of lens trauma. In patients with cataract, combined cataract and GFS may be considered.

Ptosis and Strabismus

Prevention

1.

Corneal traction suture rather than a superior rectus suture.

2.

Minimize traction on the eye which stretches the levator aponeurosis.

3.

In LBCF, dissect the conjunctiva and Tenon's as separate layers to prevent damage to the superior rectus muscle.

4.

Posteriorly placed sponges soaked in antifibrotic because MMC is toxic to the superior rectus muscle.

Management

Conservative treatment is recommended as most cases settle spontaneously, but sometimes surgery (e.g., repair of a levator dehiscence) may be required.

Astigmatism

Prevention

1.

Minimize sclerostomy size especially in eyes with low scleral rigidity.

2.

Smaller scleral flaps - but must still provide adequate resistance to aqueous outflow especially with adjuvant antifibrotics.

3.

Oblique rather than radial sutures on scleral flap.

CONCLUSION

This chapter highlights the importance of implementing a total GFS system starting from preoperative assessment, to intraoperative technique, and finally postoperative management. The first chance is the best chance of success and it is important for surgeons to understand the principles of GFS and acquire advanced techniques to tailor GFS to each individual patient. One should be prepared to change the intraoperative strategy when unexpected conditions are encountered. Communication between glaucoma surgeon and patient is of paramount importance and management of realistic patient expectation will help ensure an optimal outcome.

DOWNLOADS OF VIDEOS OF SURGERY

Videos of these techniques and associated articles can be downloaded from http://www.ucl.ac.uk/ioo/research/khawlibrary.htm.

ACKNOWLEDGMENTS

Our research has been supported by the Medical Research Council (G9330070), the Guide Dogs for the Blind, the Wellcome Trust, the TFC Frost Trust, the International Glaucoma Association, Fight for Sight, the Singapore National Medical Research Council, Moorfields Trustees, the Alcon Institute Prize, The Eranda Trust, the Haymans Trust, Ron and Liora Moskovitz, and the Michael and Ilse Katz foundation. The research also received support from the Department of Health's National Institute for Health Biomedical Research Center.

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