Ординатура / Офтальмология / Английские материалы / Glaucoma Surgery_Trope_2005

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1.INTRODUCTION

Agents that modulate healing such as the antimetabolites 5-fluorouracil (5FU) and mitomycin-c (MMC) have revolutionized glaucoma surgery, in patients with a high risk of surgical failure. There is increasing evidence from long-term prospective trials, that intraocular pressures in the 10 15 mmHg range best preserve long-term vision in glaucoma (1,2). However, vision threatening complications occur with the use of these agents (3,4).

Changes in clinical techniques of antimetabolite application can increase the safety and considerably reduce complications while maintaining effectiveness. In this chapter, we describe how our surgical technique has been changed to make the use of antimetabolites as safe as possible the Safe Surgery System. This technique has evolved at Moorfields on the basis of both clinical observation and experimental studies to reduce complications and to enhance success. Some changes in surgical technique are necessary to take full advantage of these improvements. The techniques and materials described are straightforward and have been designed to be easily available to ophthalmologists.

2.WHICH ANTIFIBROTIC AGENT(S)

There are many antifibrosis agents available for use and these range from steroids used in virtually every patient, through to antimetabolites and newer experimental agents. The full details of all antiscarring agents are too extensive for this chapter and are covered elsewhere. However, the many potential agents are summarized in Table 4.1 and the risk factors, risks of antimetabolite complications, and regimen we use in Tables 4.2 4.4.

3.CLINICALLY USED AGENTS

The most commonly used agents are 5FU and MMC, with other agents such as betaradiation occasionally used. Newer agents currently undergoing clinical trials in humans include Trabiow human antibody to transforming growth factor beta2, photodynamic therapy and suramin.

3.1.5-Fluorouracil

5FU is most commonly thought of as an agent preventing DNA synthesis and therefore cell proliferation, but it also has other effects including interference with RNA function. 5FU was first used after glaucoma filtration surgery in the 1980s by Parrish and the Miami group. More recently, 5FU has been used as a single intraoperative sponge application, stimulated in part by laboratory experiments suggesting that long-term effects of 5FU could be achieved from convenient single, short intraoperative applications in vitro and in vivo (7,8) and the the intraoperative use of MMC.

3.2.Mitomycin-c

MMC is an antibiotic antimetabolite that damages DNA by alkylation and possibly crosslinking. Free radicals are also generated that can damage many nonspecific aspects of cell function including DNA, RNA, and protein synthesis. MMC is more effective than 5FU, essentially, because at the clinical doses currently used, more cell death than cell growth arrest occurs, resulting in tissues that are relatively acellular and unable to respond to healing stimuli.

Strontium-90 probe, which is applied to the bleb area at the end of surgery. A dose of 1000 cGy is normally given the time of exposure depends on the emission rate of the probe. Trabiow is given as a subconjunctival injection of antibody just before opening the conjunctiva, at the end of surgery, on day 1 and day 7 after surgery. Beta-irradiation has also been used effectively to inhibit wound healing after filtration surgery, principally by causing cellular growth arrest (10).

A summary of the currently used intraoperative agents is shown in Table 4.5.

Table 4.3 Possible Risk Factors for Antimetabolite

Related Complications

†Elderly patient

†Primary surgery no previous medications

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

†Thin conjunctiva or sclera

†Bleb placed in interpalpebral or inferior position

Table 4.4 Moorfields Eye Hospital (More Flow) Intraoperative Single Dose Anti scarring Regimen v2005 (Continuously Evolving). Lower Target Pressures Would Suggest that a Stronger Agent May be Required

Low risk patients (nothing or intraoperative 5FU 50 mg/mL )a No risk factors

Topical medications (beta blockers/pilocarpine) Afro Caribbean (elderly)

Youth ,40 with no other risk factors

Intermediate risk patients (intraoperative 5FU 50 mg/mL or MMC 0.2 mg/mL)a 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 (intraoperative MMC 0.5 mg/mL)a

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. CAT 152 (Trabiow) or humanized anti TGF beta2 antibody may be appropriate in the low and intermediate risk groups in the future on the basis of the results of current studies. These groups account for the majority of patients undergoing glaucoma surgery. aPostoperative 5FU injections can be given in addition to the intraoperative applications of antimetabolite.

4.APPLICATION TECHNIQUE

The variations in the technique used to deliver intraoperative antimetabolites 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.

Changes in area of treatment, conjunctival and scleral flap construction, and adjustable sutures have led to a dramatic difference in terms of reducing short and long term complications (Fig. 4.1).

This has led to a reduction in cystic areas within the bleb from 90% to 29%. The blebitis and endophthalmitis rate over 3 5 years was 20% for older limbus based techniques with a smaller treatment area vs. 0% over the same period for the current technique (11). Falls in complication rate have also been seen in the USA in lower risk populations from 6% to 0.5% to date (Paul Palmberg, personal communication). If these figures were extrapolated to an approximate figure of 50,000 trabeculectomies with antimetabolite per year in the United States it is possible that bleb related complications could be avoided in many thousands of patients (Fig. 4.2).

4.1.Intraoperative Application of Antimetabolite

4.1.1.Type of Incision/Dissection

Dr. Khaw has changed to a fornix-based incision for either intraoperative 5FU or MMC. The cut length is 8 mm. He does not make a relieving incision to avoid any restricting

Note: There have been reports of 5FU given intraoperatively directly into the filtration site during surgery. However, the risk of intraocular penetration is great and commercial 5FU is alkaline with a pH 9.0. Injected MMC has also been occasionally reported but one case of combined central retinal artery and vein occlusion has been reported following MMC injection. An aliquot of 50 mL of MMC (one drop) irreversibly damages the cornea.

incision. He dissects backwards with Westcott scissors to make a pocket of 10 15 mm posteriorly and wide for the antimetabolite sponges. When he dissects over the superior rectus tendon he lifts the conjunctiva to cut attachments avoiding the tendon itself (Fig. 4.3).

Figure 4.1 (See color insert) Changes in technique leading to improvements in outcome follow ing the use of antimetabolites.

Explanation. An aqueous jet at the limbus predisposes to an anterior focal cystic bleb, whereas posteriorly directed diffuse flow of aqueous from incompletely cut sides of a large scleral flap results in a more diffuse noncystic bleb. There is also evidence that treatment under the flap increases the success rate (15). Finally, if dissection occurs before the antimetabolite treatment and if there is any defect in the flap the use of intraoperative agents, particularly mitomycin can be avoided and postoperative injections used instead.

4.1.3.Conjunctival Clamp

Dr. Khaw uses a special conjunctival T clamp he designed (Duckworth and Kent 2-686 Duckworth-and-Kent.com) to hold back the conjunctiva and to prevent antimetabolite touch. This clamp maintains a pocket for antimetabolite treatment.

Explanation. Our experiments have shown that the antimetabolite affects mainly the area it touches (8), therefore protecting the edge prevents wound leaks and dehiscence.

4.1.4.Type of Sponge

Dr. Khaw uses circular medical grade polyvinyl alcohol sponges used for lasik and corneal shields rather than other sponges. He cuts the sponges in half and folds them like a foldable lens. They fit through the entrance to the pocket without touching the sides ( 5 mm 3 and insert about 6 of these) (Fig. 4.4). He attempts to treat as large an area as he can. He also treats under the scleral flap.

He has used polyvinyl alcohol sponges for many years as they maintain their integrity and do not fragment. In contrast, other sponges (e.g., Weck Cell) fragment relatively easily, with an increased chance of leaving small pieces of sponge behind in the wound. The large area of treatment results in more diffuse noncystic blebs clinically. Dr. Khaw treats under the flap as there is evidence that it improves the success rate. In addition, when he has re-explored failed surgery he has found adhesions between the scleral flap and bed in addition to episcleral fibrosis.

Figure 4.4 (See color insert) Special clamp protecting conjunctiva while folded sponges are being inserted.