Despite rapid growth in the number of surgical options for the management of glaucoma, trabeculectomy remains the gold standard surgical procedure. Newer microstents are also being utilized to create filtering blebs, but long-term outcomes are not yet available in the literature. Here, we highlight important considerations to optimize surgical outcomes with these procedures and include a discussion of antifibrotic usage.

Postoperative Management

Immediate Postoperative Period

Early postoperative management of blebs should include topical steroids such as prednisolone acetate 1% or difluprednate 0.05% (Durezol; Novartis) every 1 to 2 hours. Steroid use can then be tapered slowly over the next 3 months, adjusted for the degree of intraocular inflammation and bleb vascularity. Topical antibiotics are often administered for the first 1 to 2 weeks, and topical cycloplegic agents may be added to deepen the anterior chamber in phakic patients.

Trabeculectomy usually includes the placement of multiple sutures to decrease aqueous outflow through the scleral flap during the immediate postoperative period. This practice optimizes scarring of the anterior conjunctival wound edge to the limbus and, in turn, reduces the risk of early bleb leak and subsequent failure. These sutures may be released using a diode laser at the slit lamp. Timing of laser suture lysis varies depending on postoperative intraocular pressure (IOP) response, target IOP range, and estimated risk of hypotony. Prior reports suggest initiating sequential laser suture lysis as early as several days postoperatively to weeks or months after surgery.^1,2 Releasable flap sutures may also be used when there is limited access to a laser or when limited visibility of sutures is anticipated.³ According to data from the Tube Versus Trabeculectomy Study, early postoperative complications are usually self-limited and do not affect long-term surgical outcomes when managed appropriately.⁴

Management of Postoperative Complications

Early postoperative hypotony occurs in up to 48% of all trabeculectomy cases.⁵ Most cases are caused by overfiltration or underproduction of aqueous. Further examination may reveal serous or hemorrhagic choroidal detachment on either indirect fundoscopy or ultrasonography. Overfiltrating blebs can usually be monitored, because most are self-limited. Intervention should be considered for severe anterior-chamber shallowing or significant, persistent choroidal effusions or hemorrhage. Cohesive viscoelastic may be injected into the anterior chamber to slow flow through the sclerostomy flap; alternatively, a symblepharon ring or Simmons tamponade shell may be placed to mechanically limit the surface area of the bleb and degree of filtration. Cases in which conservative management fails may require additional sutures to be placed to close the scleral flap in the operating room.

Wound leaks are marked by Seidel positivity in a low-lying or flat bleb. Applying gentle pressure to the globe can identify a slow leak in a hypotonous eye. Wound leaks are estimated to occur in up to 20% of all trabeculectomies.⁶ Slow, localized leaks may be managed with a large-diameter contact lens in the early postoperative period. However, a flat bleb may necessitate early conjunctival closure, either with suture placement at the slit lamp or early reoperation. The risk of subsequent bleb fibrosis and failure may increase without timely intervention.

Use of Antifibrotics

Early surgical outcomes of trabeculectomies were found to be limited by postoperative fibrosis — most commonly due to episcleral flap scarring. Therefore, appropriate use of antifibrotics is key to maximizing the chance of good surgical outcomes. According to a survey conducted by the American Glaucoma Society, the majority of glaucoma specialists now use antifibrotics for trabeculectomies.⁷

Postoperative Antifibrotic Use

The antimetabolite 5-fluorouracil (5-FU) inhibits pyrimidine metabolism. In vivo, 5-FU has a short half-life that may be titrated easily to clinical response. According to the Fluorouracil Filtering Surgery Study, trabeculectomies with multiple repeated postoperative subconjunctival 5-FU injections significantly increased bleb longevity and reduced rates of reoperation, especially among patients with prior histories of intraocular surgery.^8-10

By contrast, mitomycin C (MMC) is an alkylating agent that cross-links DNA, thereby preventing both DNA replication and translation.¹¹ Mitomycin C is more potent than 5-FU, and therefore it usually requires fewer injections postoperatively. Alternative methods of MMC application have been described, including direct application of MMC-soaked sponges to the trabeculectomy site postoperatively.¹²

Intraoperative Antifibrotic Use

Intraoperative application of antifibrotics reduces the need for postoperative injections and also may be preferable to patients. Both Singh et al and WuDunn et al found that intraoperative application of either 5-FU at 50 mg/mL for 5 minutes or 0.4 mg/mL MMC for 2 minutes led to similar rates of postoperative IOP-lowering medication burden, final visual acuities, and complications.^13,14

Longer-term studies suggest that, although intraoperative 5-FU may lead to surgical success at the first postoperative year, these effects are not maintained into the second postoperative year.¹⁵ Among patients at higher risk for bleb failure, those who receive intraoperative 5-FU may be less likely to achieve low IOPs, regardless of whether postoperative 5-FU injections are administered. By contrast, intraoperative application of 5-FU may both reduce the burden of postoperative 5-FU injections among patients at lower risk for bleb failure and allow for low postoperative IOPs.

Surgical success among patients receiving intraoperative MMC is reportedly higher. Prior studies suggest that, after 3 years, 70% to 82% of patients were able to achieve an IOP lower than 22 mmHg with medications; 50% to 73% of patients were able to reach this goal without a medication requirement.^16,17 Reibaldi et al reported that even lower doses of MMC (0.2 mg/mL x 2 min) can still lead to more than 40% of patients achieving an IOP less than 22 mmHg without glaucoma medications.¹⁸ Therefore, surgeons may consider using 5-FU for patients deemed to be at low risk for bleb failure, whereas MMC may be reserved for those at higher risk for failure.

Revision of Trabeculectomy

Antifibrotic agents may also be employed to rescue a failed or failing trabeculectomy. If scarring is identified early enough, and a bleb is still present, subconjunctival 5-FU can be injected 180° away from the surgical site to rescue trabeculectomies at risk for early failure.²¹

For flat-appearing blebs, revision of the trabeculectomy is often required. After injecting MMC posterior to the scarred bleb, a 25-gauge bent needle or microvitreoretinal blade can be advanced beneath the conjunctiva to the posterior edge of the scleral flap. Once the flap is elevated, an immediate egress of aqueous will be seen, and a diffuse bleb should form. Steroids should be used in the postoperative period for several months to enhance the chances of bleb survival following this procedure.

Complications of Antifibrotic Use

Although antifibrotics may be more likely to lead to sustained IOP lowering postoperatively, they also increase the risk of hypotony. Postoperative hypotony is more commonly reported among patients receiving MMC; however, reported rates vary widely, ranging from 1.3% to 42.2%.^22,23

Use of antifibrotic agents — especially MMC — can result in thin-walled, avascular blebs that predispose patients to developing late bleb leaks.^24,25 Additionally, these late bleb leaks are associated with higher rates of endophthalmitis among patients who have received antifibrotics.^26,27

A common complication of 5-FU injection is corneal epithelial toxicity leading to corneal abrasions and, less frequently, persistent corneal epithelial defects. Rates of these effects can be minimized with fewer postoperative injections.²⁸

Other Agents and Methods

There are few studies on the efficacy of alternative antifibrotic agents. However, studies of daunorubicin (Cerubidine; Hikma) and bleomycin (Blenoxane; Bristol-Myers Squibb) do not appear to clearly demonstrate benefit in the context of trabeculectomy survival.

CAT-152 (Cambridge Antibody Technology) is a transforming growth factor-β2 inhibitor that is currently under investigation as a newer antifibrotic agent for trabeculectomy. By specifically targeting transforming growth factor-β2, the risk of toxic ocular side effects may be limited. In rabbits, CAT-152 has been found to produce diffuse, elevated, fleshy blebs and increase bleb survival without affecting surrounding conjunctival tissue histologically. However, subconjunctival injections of CAT-152 administered in both the immediate preoperative and postoperative period failed to increase bleb survival more than balanced saline solution injections.²⁹

Minimally Invasive Glaucoma Surgery-Assisted Blebs

Minimally invasive glaucoma surgery (MIGS) involves procedures that aim to bridge the gap between topical glaucoma therapies and incisional glaucoma surgeries. Although the range of MIGS procedures continues to grow, devices that assist in bleb formation will be reviewed briefly below.

The Xen gel stent (Allergan) is composed of porcine gelatin and designed to shunt aqueous from the anterior chamber to the subconjunctival/sub-Tenon space. Xen gel stents may be inserted ab interno or ab externo, with or without conjunctival dissection, and they are often supplemented with subconjunctival injection of an antifibrotic agent. The 45-µm lumen diameter is designed to limit aqueous outflow and to decrease the risk of persistent hypotony. Early prospective studies on Xen gel stents suggest that up to 50% of Xen-assisted blebs require bleb needling.^30,31 Up to 40% of blebs associated with Xen stents may be associated with early-onset leaks.³² Less common complications, including dislocation of stents into the anterior chamber, accidental stent amputation, and endophthalmitis, have been reported.^33-35

The Microshunt (Santen) is composed of a synthetic polymer of poly(styrene-block-isobutylene-block-styrene). Similar to the Xen gel stent, the Microshunt has a 70-µm lumen that aims to limit fluid outflow. The Microshunt is designed to be implanted in an ab externo fashion and also requires the use of MMC. The shunt has small tabs that are used to secure the device into a shallow scleral pocket, and it connects the anterior chamber to the sub-Tenon space. Studies suggest that up to 13% of cases may have transient hypotony.^36,38 According to one published study, just under 9% of Microshunt blebs become encapsulated and require postoperative needling within the first 3 months postoperatively.38 Less common complications include transient hyphema (8%) and vitreous hemorrhage (4%).^36-38

Conclusion

Since their first description by Cairns in 1968, techniques for optimizing trabeculectomy success have evolved significantly.³⁹ With good surgical technique, close postoperative follow-up, and aggressive management, trabeculectomies can achieve excellent long-term IOP-lowering outcomes. Furthermore, judicious use of antifibrotic agents in the perioperative and postoperative periods can augment surgical success. Long-term surgical success with newer microstents still needs to be determined. GP

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Joseph F. Panarelli, MD, is a glaucoma specialist at NYU Langone Health in New York, New York. He reports consultancy to Aerie Pharmaceuticals, New World Medical, Allergan, Santen, and Glaukos, and speaker's fees from Aerie Pharmaceuticals and Allergan. Reach him at joepanarelli@gmail.com.

Rachel Lee, MD, is an ophthalmology resident at New York Eye and Ear Infirmary in New York, New York. She reports no related disclosures.