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When glaucoma progresses despite maximal medical and laser therapy, the patient often undergoes surgery. For the most part, trabeculectomy with or without adjunctive antimetabolites is the first-line treatment. The goal of this intervention is to lower the IOP sufficiently to halt disease progression. Unfortunately, some trabeculectomies fail and actually cause the IOP to increase. The most common cause of bleb failure is episcleral fibrosis or subconjunctival scarring.

In these cases, the surgeon can lyse or release the scleral sutures and institute digital ocular pressure. Sometimes, the IOP will remain high. Although recommencing medical therapy is an option, the drugs' inability to lower the IOP adequately was an impetus for trabeculectomy. Cost and patients' adherence to prescribed medical therapy are additional issues.

Bleb needling is an alternative to surgically revising the bleb, repeating trabeculectomy, or implanting a tube shunt.

HISTORY
In 1941, Ferrer1 described conjunctival dialysis, which consisted of incising the scar tissue and then separating the conjunctiva from the sclera with a spatula. His article is likely the first account of bleb revision. Later, Pederson and Smith2 reported 69% success in needling encapsulated blebs, but they noted that a high percentage of the eyes also underwent medical therapy.

As ophthalmologists began administering antifibrotics during glaucoma surgery, reports of the agents' use in bleb needling appeared. Ewing and Stamper3 were the first to describe the use of 5-fluorouracil (5-FU) in bleb needle revisions. They performed subconjunctival injections of 5-FU during the postoperative period and reported a 91.6% success rate with 63.6% (11 of 12 patients) requiring adjunctive medications. Shin et al4 administered single injections of 5-FU at the time of bleb needling and reported an 80% success rate (24 of 30 patients) with the IOP controlled in 21% of those eyes without additional medications. They also noted higher success with longer intervals between trabeculectomy and additional needling. In 1996, Mardelli et al5 described bleb needling as a slit-lamp procedure using injections of mitomycin C (MMC). They reported an overall success rate of 92% and commented that raised, quiet blebs responded better than inflamed, injected blebs.

In their retrospective study, Shin et al6 found three significant risk factors for failed 5-FU needling: (1) an IOP higher than 30 mm Hg before needling; (2) no MMC used during previous trabeculectomy; and (3) an IOP greater than 10 mm Hg immediately after needling. Broadway et al7 studied the use of 5-FU prospectively and reported that an immediate reduction in IOP to less than 11 mm Hg was favorable to the long-term efficacy of bleb needling. Recently, Gutierrez-Ortiz et al8 published a prospective study showing that MMC needling was more successful if performed within 4 months of trabeculectomy.

There are some controversial points regarding bleb needling in the literature. Comparing studies is challenging due to variations in inclusion criteria and definitions of success as well as the low number of prospective, randomized, controlled trials on the subject.

TIMING AND PATIENT SELECTION: OUR APPROACH
We needle failing blebs in patients with IOPs above target for their level of glaucomatous damage. In assessing a bleb's function, we consider its appearance, elevation and extent as well as the presence of microcysts and the vascularity on and around the bleb (Figure 1). Functioning blebs exhibit diffuse, regular elevation, microcysts, and mild vascularity. A failing bleb can appear flat and thickened or thin. Alternatively, it may be shaped like a dome with surrounding thick vessels, and microcysts may be absent.

Figure 1. A patient experiences early encapsulation of the bleb. Note the elevation of the bleb and the thick vessels surrounding it.

When a bleb is failing and the IOP increases, we first try laser suture lysis times two (we place two scleral sutures) with or without posterior digital ocular massage. In many cases, this approach allows for the reformation and remodeling of the bleb. When these measures are ineffective, we generally needle the bleb rather than restart drug therapy.

It is important to rule out an obstruction at the sclerostomy site that may be causing resistance to flow. The clinician should perform gonioscopy to rule out causes of the internal obstruction of the sclerostomy site. If iris, vitreous, or other matter is obstructing the opening, then needling will not work, and another approach will be necessary to remedy the problem. Needling can restore function to the bleb when the failure is caused by episcleral subconjunctival fibrosis.

TECHNIQUE
Setting
Surgeons may perform a needling revision in the OR or in their offices. The OR offers the advantage of a more controlled setting and may allow for more extensive treatment. Nevertheless, we routinely needle blebs in the office at the slit lamp and believe the procedure may be thus executed with high success and minimal to no discomfort to the patient. The advantage of an office procedure is mainly avoiding another visit to the OR.

Our Approach
Surgeons use a variety of techniques. A description of our approach follows. After obtaining informed consent, we administer a drop of a fourth-generation fluoroquinolone followed by a generous application of topical lidocaine 2% gel over the bleb to be needled (intraoperatively, we reapply the gel as needed). We then wait 5 minutes, during which time a nurse draws 0.1 mL of MMC 0.04 mg/mL into a 1-mL tuberculin syringe. We should note that this concentration is 10 times less than what we typically use during the primary procedure. Surgeons should ensure that they have received the correct concentration of MMC from the pharmacy.

With the patient seated at the slit lamp, we place a sterile lid speculum and inject the MMC subconjunctivally with a 30-gauge needle, which enters the conjunctiva bevel up approximately 5 to 10 mm from the bleb site and is posteriorly directed. Normally, we perform the injection from the temporal side of the bleb for an easier approach. We distribute the MMC with the aid of a cotton swab by applying pressure in a rolling motion over the conjunctiva next to the injection site.

After removing the lid speculum, we place a 25-gauge needle on a 1-mL syringe and use its cap to bend the needle at its base to approximately 60º. Fifteen to 20 minutes after injecting the MMC, we replace the lid speculum and reenter the subconjunctival space at the same location. We introduce the needle bevel up and move it to and fro in an attempt to disrupt all scar tissue in the sub-Tenon's space (Figure 2). Our aim is to improve the flow posteriorly, so we puncture the wall of the bleb multiple times, especially posteriorly, away from the limbus. The goal of the procedure is to increase the permeability of the bleb's wall and thus produce a more diffuse, better functioning bleb. We keep the needle bevel up over the scleral flap and are extremely careful not to create a conjunctival buttonhole.

Figure 2. The surgeon passes a prebent 25-gauge needle into the subconjunctival space, and it punctures the bleb's wall upon entry. Movements to and fro disrupt the scar tissue. The surgeon advances the needle to the other side of the bleb and posteriorly and then uses the instrument to puncture the thickened wall of the bleb several times.

Multiple passes of the needle are typically necessary to revive the bleb. Ideally, all of the needling is performed from a single site, but it is sometimes necessary to approach the bleb from both sides (temporally and nasally). If the maneuver is successful, the bleb will change its appearance during the procedure (Figure 3). Specifically, flat blebs will grow more elevated, and encapsulated blebs will become more diffuse. The bleb's changing appearance indicates the restoration of aqueous flow.

Figure 3. After needling, the bleb appears flatter and more diffuse. The IOP improves.

In some cases, it is necessary to lift the scleral flap with the needle and enter the anterior chamber to restore the flow of aqueous. This situation may arise if the bleb is flat with a visible scleral flap and does not respond to episcleral needling. The surgeon should lift a scarred-down scleral flap if it is the main cause of resistance.

At the end of the procedure, we instill fluorescein to check for bleb leaks. Holding a cotton swab in place for 1 minute usually stems leakage at the injection site. We also measure the IOP. Low pressures are promising. Several studies have found a correlation between an immediate reduction in IOP to less than 11 mm Hg and a higher rate of success.6-8

Postoperatively, we prescribe prednisolone 1% q.i.d. and follow up with the patient in 1 week. Normally, we see him every 1 to 2 weeks until a stable, well-functioning bleb is present. We repeat needling with MMC if necessary up to three times, depending on the initial response. In most if not all studies, success was achieved with more than one needling procedure.

Variations
Some surgeons administer unpreserved lidocaine 1% before the MMC so that the lidocaine is injected first, both for anesthetic purposes and to create a wheal (or elevated region of conjunctiva) under which to safely inject the MMC. One may use other needles from 25 to 30 gauge for this procedure. We favor the 25-gauge needle because it is sturdier and more resistant to bending during the disruption of scar tissue.

In addition, surgeons have proposed using medications other than MMC and 5-FU. Tham et al9 conducted a pilot study on intrableb injections of triamcinolone after bleb-forming glaucoma surgery, and Kahook et al10 published a case report on the subconjunctival injection of bevacizumab in encapsulated blebs. Additionally, Iwach et al11 suggested the transconjunctival administration rather than subconjunctival injection of MMC. We prefer MMC primarily because we feel that it is more comfortable to the patient and less toxic to the corneal epithelium than 5-FU. We also feel that MMC is more potent and effective than 5-FU and that it thus requires fewer follow-up injections.

CONCLUSION
Although less invasive than trabeculectomy, bleb needling should be performed with caution. Possible complications include hyphema, a flat anterior chamber, choroidal effusions, conjunctival buttonholes, and endophthalmitis.2,5,8 Nonetheless, needling can be an effective means of rescuing failing procedures and can delay or prevent a return to the OR. Despite many variations in the technique and adjunctive medications used for bleb needling, surgeons can improve their outcomes with trabeculectomy if they follow guiding principles such as those outlined in this article.

Larissa Camejo, MD, is a fellow at the Department of Ophthalmology at the University of Pittsburgh. Dr. Camejo may be reached at (412) 647-2152; camejol@upmc.edu.

Robert J. Noecker, MD, MBA, is Director of the Glaucoma Service and Associate Professor/Vice Chair at the Department of Ophthalmology at the University of Pittsburgh. Dr. Noecker may be reached at (412) 647-2152; noeckerrj@upmc.edu.

1. Ferrer H. Conjunctival dialysis in the treatment of glaucoma recurrent after sclerectomy. Am J Ophthalmol. 1941;24:788-790.
2. Pederson JE, Smith SG. Surgical management of encapsulated filtering blebs. Ophthalmology. 1985;92:955-958.
3. Ewing RH, Stamper RL. Needle revision with and without 5-FU for the treatment of failed filtering blebs. Am J Ophthalmol. 1990;110:254-259.
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8. Gutierrez-Ortiz C, Cabarga C, Teus MA. Prospective evaluation of preoperative factors associated with successful mitomycin C needling of failed filtration blebs. J Glaucoma. 2006;15:98-102.
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10. Kahook MY, Schuman JS, Noecker RJ. Needle bleb revision of encapsulated filtering bleb with bevacizumab. Ophthalmic Surg Lasers Imaging. 2006;37:148-150.
11. Iwach AG, Delgado MF, Novack GD, et al. Transconjunctival mitomycin-C in needle revisions of failing filtering blebs. Ophthalmology. 2003;110:734-742.