Glaucoma is an optic nerve disease and a leading cause of irreversible blindness. An increase in intraocular pressure (IOP) is the most important risk factor for glaucoma progression, and lowering of IOP is the most effective treatment to prevent glaucoma progression [1] . Trabeculectomy is the most popular surgical procedure for lowering IOP in patients with glaucoma refractory to medical and laser treatment, particularly primary open angle glaucoma (POAG) and normal tension glaucoma (NTG) [2] .

Most trabeculectomies achieve successful outcomes and reduce IOP over the long-term, thereby minimizing progression of glaucoma [2] [3] . Maintenance of adequate aqueous outflow through the fistula is essential to prevent bleb failure. The size of the scleral flap and internal sclerostomy are the most important factors determining the amount of aqueous flow as well as the thickness of the scleral flap. Although more aqueous outflow results in a lower IOP, over filtration of the aqueous humor leads to hypotony and complications including maculopathy and choroidal detachment. It is important to make the scleral flap sufficiently large to cover the inner sclerotomy to prevent over filtration. Today, most surgeons create a 3 - 4-mm-wide half-layer scleral flap and a 1.0 - 1.5-mm deep sclerostomy during the surgery [4] [5] [6] [7] [8] .

However, some trabeculectomies fail to achieve long-term IOP control because of scar formation at the level of the conjunctiva tenon-episcleral interface, the scleral flap, its overlying episclera, or the sclerostomy [9] [10] . Despite increasing use of mitomycin-C or 5-fluorouracil, several studies have reported that the rate of bleb failure is 10% - 20% [11] [12] . The most common causes of bleb failure are scar formation and closure of the fistula [13] . Bleb failure results in elevated IOP and progression of visual field (VF) loss, which are fatal to eyes with advanced glaucoma.

We have performed low target pressure trabeculectomy (LTT) in patients with advanced glaucoma to increase postoperative aqueous outflow by modifying the inner sclerostomy size and tension of the sutures to minimize bleb failure. In this study, we assessed the efficacy and safety of LTT compared with that of conventional trabeculectomy (CT) in terms of success rate and surgical complications.

Thirty-nine consecutive eyes from 34 patients who underwent trabeculectomy by an experienced glaucoma specialist (S.J.H.) between August 2010 and August 2015 were enrolled. The medical records of these patients were reviewed retrospectively. This study adhered to the tenets of the Declaration of Helsinki.

The Institutional Review Board (IRB)/Ethics Commitee approval was obtained for this retrospective study, and informed consent was obtained from all participants before surgery. We included only patients with advanced glaucoma who were diagnosed with POAG or NTG and had completed the 2-year follow up. Patients who underwent previous ophthalmic surgery except phacoemulsification were excluded.

Trabeculectomy is a widely performed glaucoma filtration surgery. Many possible complications can occur after a trabeculectomy procedure. Surgical failure is the most common complication, resulting in high postoperative IOP and subsequent progression of VF defects and blindness [3] .

In the present study, the success rate in the LTT group was significantly higher than that in the CT group in terms of complete success and qualified success with each criterion. Our definition of “qualified success” was different from those of previous studies. Previous studies defined “qualified success” as surgical success with or without medication [14] . Because we performed the LTT to increase aqueous outflow through the fistula, we intended to compare the pure IOP-lowering effect of the CT and LTT. We used a different concept of

LTT = Low target trabeculectomy; CT = Conventional trabeculectomy; IOP = Intraocular pressure; Qualified success: success without additional medication regardless of 5-flurouracil needling; Complete success: success without IOP-lowering procedure or additional medication; *From Kaplan-Meier survival analysis; †P < 0.05.

LTT = Low target trabeculectomy; CT = Conventional trabeculectomy; A/C = anterior chamber; Decreased vision¹⁾: loss of more than three Snellen lines; *Fishe’s exact test.

“qualified success” to exclude the IOP-lowering effect of the medication itself. Therefore, we defined “qualified success” as surgical success requiring the 5-FU needling procedure to maintain IOP below target pressure without additional medication.

The qualified success rate in the CT group was 76.5% with the IOP criterion ≤18 mmHg. This result is comparable with previous reports. Even if IOP remains high normal, it can lead to further optic nerve damage, VF progression, and legal blindness due to IOP fluctuations [15] . Thus, maintaining a relative low IOP is important to minimize disease progression, particularly in patients with advanced glaucoma. We performed the LTT to achieve those goals. During the operation, large inner sclerostomy and controlled scleral flap sutures allowed more aqueous flow through the fistula. LTT decreased postoperative IOP, and increased survival rate using those techniques., Postoperative IOP in the LTT group was 6.75 ± 1.42 mmHg on the first postoperative day and 10.25 ± 1.87 2 years after surgery. The difference in postoperative IOP between the LTT and the CT groups was significant. Postoperative IOP in the LTT group was approximately 5.8 mmHg lower than that in the CT group.

LTT showed better efficacy than that of CT in terms of postoperative IOP. However, over filtration of the aqueous humor can lead to postoperative complications such as hypotony, a shallow anterior chamber, and late bleb leaks. De Bry et al. reported a 6.0% annual incidence of bleb leaks following trabeculectomy with mitomycin C [16] . Another study reported 10.6% incidence of symptomatic hypotony with limbus-based trabeculectomy, and that of bleb leak to be 0.4% in the first 6 weeks after surgery and 4.1% at 6 weeks after surgery. In our study, no eye developed symptomatic hypotony or a shallow anterior chamber that persisted for longer than 3 days. An early postoperative bleb leak developed in one eye in the LTT group, and one eye in the CT group. However, late-onset leak developed in only two (16.7%) eyes in the LTT group whereas none in the CT group.

Several studies have reported treatment for late-onset bleb leaks. Hide to et al. controlled late-onset bleb leaks conservatively [17] . Autologous blood injection and amniotic membrane transplantation are frequently performed for late-onset bleb leaks [18] [19] [20] . In our cases, two eyes were treated completely with autologous blood injection and subsequent amniotic membrane transplantation (Figure 3). After treatment, IOPs were < 12 mmHg, and no subsequent leaks developed during the follow-up period.

Three eyes in the LTT group and four eyes in the CT group lost vision of more than three Snellen lines during the early postoperative period. However, no eye lost vision at all in the 2 months after surgery. In our study, no bleb-related infection was observed during the study period. This result was comparable with the previously reported incidence of bleb-related infection of 0.5% - 1.0% per year [3] [21] .

In our experience, various types of LTT blebs develop according to the ages and tenon tissue states of patients. Regardless of outer bleb shape, intra-bleb

morphology of LTT blebs showed greater sub-bleb fluid collection than that of a CT bleb. The walls of a LTT bleb seemed to be thinner than those in the CT group, and revealed more multiple sponge-like microcystic changes in the conjunctiva-tenon complex (Figure 4). Because a limited number of anterior segment optical coherence tomography scans of the bleb were obtained postoperatively, we were unable to provide a statistical comparison of bleb morphology between the two groups. A morphologic analysis of the bleb may help explain the difference in postoperative IOP and the incidence of bleb-related complications between the two groups.

We have experienced several cases of blindness resulting from bleb failure in patients with advanced glaucoma before this study. This is why we performed the more aggressive surgery for patients with advanced glaucoma. This retrospective case series was too small to conclude the safety and efficacy of LTT. Despite this limitation, our study demonstrates that LTT was superior to CT in terms of maintaining low IOP all over the day and night. Furthermore, the incidence of postoperative complications was not different between the two groups, and no vision-threatening complications developed.

Another limitation of this study was the absence of a VF progression analysis. We included patients with advanced glaucoma who underwent trabeculectomy. A preoperative VF test was performed several times before surgery in all patients, but the 2-year postoperative test was absent in some patients. Therefore, we could not compare the rate of disease progression between the two groups. In

addition, the LTT group was comprised of patients with more advanced glaucoma than those in the CT group, in terms of the mean preoperative MD value. These reasons prevented us from comparing the efficacy of LTT and CT in terms of disease progression. However, we can speculate that LTT was better option able to prevent glaucoma progression than that of CT when we took into consideration postoperative IOP.

In conclusion, our results show that LTT was more efficient to lower IOP in patients with advanced glaucoma and did not compromise the safety of the surgery compared with that of CT. This aggressive surgical method is a good treatment option in patients with uncontrolled advanced glaucoma accompanied by small residual visual field.

This work was supported by the Soonchunhyang University Research Fund.
The funding organization had no role in the design or conducted of this research. The author declares no competing interests.

The author declares no conflicts of interest.

Ha, S.J. (2018) Efficacy and Safety of Low Target Pressure Trabeculectomy: 2-Year Clinical Results. Open Journal of Ophthalmology, 8, 42-53. https://doi.org/10.4236/ojoph.2018.81007