Same-site trabeculectomy with mitomycin and Ologen™ following failed non-penetrating deep sclerectomy

Abstract

Purpose

To assess the effectiveness and safety of same-site trabeculectomy (TRAB) with mitomycin C (MMC) and Ologen™ (Aeon Astron Europe BV. Leiden, The Netherlands) in patients with a failed non-penetrating deep sclerectomy (NPDS).

Methods

A retrospective study of 24 consecutive eyes (22 patients) undergoing reintervention by same-site TRAB with at least one-year follow-up after failed NPDS. Mean visual acuity (VA), intraocular pressure (IOP) and use of glaucoma medications were compared before and one year after surgery. Early and late postoperative complications were registered. Kaplan-Meier survival analysis was performed according to four levels of success criteria.

Results

Overall the mean IOP reduced significantly (24.9 ± 7.1 vs. 14.4 ± 4.5 mmHg; p < 0.001), and the number of glaucoma medications (2.80 ± 1.01 vs. 0.55 ± 0.94; p < 0.001) significantly decreased, one year after surgery. The mean VA remained stable one year after surgery (p = 0.516). Hypotony, defined as IOP ≤ 5 mmHg, in the early postoperative period was observed in 62.5% of eyes, but only in 2 patients (8.33%) in the long term. The mean survival time ranged from 10 months (CI 95% 5–15) to 29 months (CI 95%: 26–32) according to the most stringent and lenient success criteria respectively.

Conclusion

Same-site TRAB augmented with MMC and Ologen™ may provide an effective, safe and lasting alternative following failed NPDS, especially when sparing of the conjunctiva is highly desirable. Postoperative hypotony is the most common postoperative complication.

Keywords

GLAUCOMA open angle glaucoma glaucoma incisional surgery anti-fibrotic agents glaucoma medical therapies

Introduction

Glaucoma is one of the leading causes of irreversible vision loss and is expected that the number of affected patients will increase from 65 to 111.8 million by 2040.¹ Intraocular pressure (IOP) is the only modifiable risk factor, and its reduction remains the basis of the treatment.

Nonpenetrating deep sclerectomy (NPDS) is a filtering surgical technique used to lower the IOP in medically uncontrolled open-angle glaucoma. NPDS has shown to be effective in long-term IOP reduction.² Compared with trabeculectomy (TRAB), NPDS has a better safety profile attributed to its lack of penetration in the anterior chamber (AC) of the eye and the absence of iridectomy.³ Concerning effectiveness, the evidence is controversial; while some studies report comparable results others show a greater IOP reduction with TRAB.⁴

The success rate of NPDS has been limited postoperatively by insufficient aqueous humor filtration.^5,6 Nd:YAG laser goniopuncture may be useful in these cases.⁷ However, some patients will need additional procedures, such as bleb needling and antimetabolite administration.⁸ In spite of all these measures, NPDS can fail, and another surgery may be required.

There has been a lack of consensus among glaucoma surgeons to indicate the best surgical option for these eyes.^9,10 A new intervention in a different location from the failed TRAB^10,11 or NPDS^10,12 has been described. Díaz-Aljaro reported the same-site deep sclerectomy (ssDS), which restores aqueous humor filtration while sparing conjunctiva that may be required for subsequent procedures.¹³ In ssDS, a conjunctival flap is dissected and mitomycin C (MMC) 0.02% is applied for 1 min. Then, the NPDS scleral flap is re-dissected and an Ologen™ matrix (Aeon Astron Europe BV. Leiden, The Netherlands) is placed under the scleral flap and under the conjunctiva, communicating both spaces.

Same-site TRAB with MMC augmentation has been described after failed glaucoma surgery including previous TRAB^9,14 or NPDS.⁹ In the current study, we describe TRAB with MMC and Ologen™ in the same location where NPDS was performed, which may constitute an alternative to ssDS when sparing of the conjunctiva is desired. The aim of this study is to assess the effectiveness, safety and survival curve of this surgical technique.

Materials and methods

This is a retrospective study of consecutive patients having an uncontrolled primary open-angle glaucoma after a prior failed NPDS, who underwent same-site TRAB with MMC and Ologen™ at the Hospital Universitario Ramón y Cajal (Madrid, Spain) from January 2017 to June 2019 with at least one-year follow-up. Only eyes with unsuccessful Nd:YAG laser goniopuncture or needling or no indication for these procedures were included. The study adhered to the tenets of the Declaration of Helsinki and was approved by the local Ethical Committee.

Data collected included laterality, sex, age, the date of procedure, prior glaucoma surgery, time from NPDS to same-site TRAB, combined phacoemulsification with same-site TRAB, visual acuity (VA), IOP and number of anti-glaucoma medications preoperatively and in each postoperative visit (1 day, 1 week, 1, 3, 6 and 12 months). Postoperative complications were also recorded and were classified in early (before the first month after surgery) and late (during the rest of the follow-up). Subsequent procedures were also registered. Data from the 24-month postoperative visit were also recorded and employed in the survival analysis if available.

Primary outcome variables were VA, IOP and number of glaucoma medications one year after same-site TRAB. Secondary outcome variables were complications and surgical success rate one year after same-site TRAB. Four levels of success criteria were defined: A (final IOP ≤ 12 mmHg and one of the following: ≥30% reduction of IOP or reduction of 2 anti-glaucomatous medications), B (final IOP ≤ 15 mmHg and one of the following: ≥25% reduction of IOP or reduction of 1 anti-glaucomatous medication), C (final IOP ≤ 18 mmHg and one of the following: ≥20% reduction of IOP or reduction of 1 anti-glaucomatous medication) and D (final IOP ≤ 21 mmHg and one of the following: ≥20% reduction of IOP or reduction of 1 anti-glaucomatous medication). Eyes with 2 or more Snellen lines of VA loss, serious complications or new glaucoma surgery were considered unsuccessful independently of IOP reduction.

Surgical technique

All eyes underwent same-site TRAB under peribulbar anesthesia by one experienced surgeon (FJMN). A fornix-based conjunctival flap was fashioned where failed NPDS had been performed. Subconjunctival local anesthetic was injected in the fibrotic area to facilitate tissue dissection. Gentle diathermy was applied in the limits of the old scleral flap and a 5 × 5 mm incision in the failed NPDS flap borders was performed. The implant used in failed NPDS was removed. MMC 0.2 mg/mL soaked sponges were applied for 2 min between conjunctiva and sclera and under the new scleral flap before entering into the AC. If indicated, combined cataract surgery was performed through a 2.2 mm corneal incision. Then, a rectangular resection of the trabeculodescemetic window, narrower than the scleral flap, was performed, followed by a basal iridectomy. A half-moon-shaped piece of 12 mm(D) × 1 mm(H) Ologen™ implant was placed under the scleral flap sticking out from its borders (Figure 1(a)). The scleral flap was sutured with four 10/0 Nylon sutures, two of them in the posterior corners of the scleral flap and two of them in each anterior lateral border of the scleral flap. The rest of the Ologen™ implant was placed between the scleral flap and the conjunctiva (Figure 1(b)). Finally, the conjunctiva was sutured with watertight 10/0 nylon sutures and dexamethasone and cefazolin were injected subconjunctivally. Postoperatively, patients were prescribed topical ketorolac for 3 months, topical tobramycin for one week and topical dexamethasone 6 times a day tapered weekly for a minimum of 2 months.

Statistical analysis

For a 0.05 level of significance and statistical power of 0.9, we estimated a required sample size of 20 patients.¹⁵ Data were described in terms of mean ± standard deviation (SD), percentages and number of cases when appropriate. Shapiro-Wilk test was applied to test the normality of the data. Student’s t-test or Wilcoxon tests were performed on paired parametric or non-parametric data as appropriate. P-values < 0.05 were considered statistically significant. Kaplan-Meier survival analysis was performed according to the success criteria previously defined. All statistical calculations were done using SPSS (Statistical Package for the Social Science; SPSS Inc., Chicago, IL, USA) version 15 for Microsoft Windows.

Results

All the patients that underwent same-site TRAB following failed NPDS over the study period met the inclusion criteria. Demographic data are shown in Table 1. 24 eyes of 22 patients underwent same-site TRAB with MMC and Ologen™ at the Hospital Universitario Ramón y Cajal from January 2017 to June 2019. The mean time from NPDS to same-site TRAB was 4.1 ± 2.3 years. In 5 eyes (20.83%), a history of glaucoma surgery apart from NPDS was found. In addition, 12 eyes (50%) underwent Nd:YAG laser goniopuncture and 7 eyes (29.17%) needling after NPDS failure. In 6 eyes (25%) a combined phacoemulsification and same-site TRAB procedure was performed. In 17 eyes data from the 24-month postoperative visit were available and included in the survival analysis.

Table 1.

Baseline characteristics of the eyes included in the study.

Number of eyes	24
Number of patients	22
Age in years (mean ± SD)	69.21 ± 10.97
Gender (males) (No. (% eyes))	12 (50%)
Ocular characteristics
Visual field
MD	−15.08 ± 6.69
VFI	60% ± 25%
Central corneal thickness	528.24 ± 49.19
Spherical refractive error	−0.60 ± 1.62
Glaucoma procedures additional to NPDS (No. (% eyes))	5 (20.83%)
TRAB	1 (4.17%)
NPDS	2 (8.33%)
Ahmed valve	1 (4.17%)
MIGS	2 (8.33%)
Nd:YAG laser goniopuncture previous to same-site TRAB	12 (50%)
Needling previous to same-site TRAB	7 (29.17%)
Time from NPDS to same-site TRAB in years (mean ± SD)	4.08 ± 2.34
Combined phacoemulsification with same-site TRAB (No. (% eyes))	6 (25%)
Visual Acuity Snellen (mean ± SD)	0.54 ± 0.34
Intraocular pressure mmHg (mean ± SD)	25.17 ± 7.23
Number of glaucoma medications (mean ± SD)	2.88 ± 0.95

No: number; SD: Standard Deviation; MD: Mean deviation; VFI: Visual Field Index; TRAB: trabeculectomy; NPDS: Non-Penetrating Deep Sclerectomy; MIGS: Minimally Invasive Glaucoma Surgery; Nd:YAG: neodymium-doped yttrium aluminum garnet.

Effectiveness analysis

VA, IOP and use of anti-glaucoma medications preoperatively and during the follow-up are shown in Table 2. Compared with baseline, VA remained stable one year after surgery (p = 0.516). There was a significant drop in mean IOP from 24.9 ± 7.1 mmHg at baseline to 14.4 ± 4.5 mmHg one year after surgery (p < 0.001). There was also a significant decrease in the number of medications from 2.80 ± 1.01 preoperatively to 0.55 ± 0.94 one year after surgery (p < 0.001). Seventeen eyes (70.83%) did not need any medication one year after surgery.

Table 2.

Preoperative and postoperative visual acuity, intraocular pressure and glaucoma medications at different postoperative visits (mean ± sd; mean variation from preoperative visit ± sd; mean % of variation from preoperative visit ± sd).

	Visual acuity (Snellen)	Intraocular pressure (mmHg)	Glaucoma medications (No.)
Preoperative	0.48 ± 0.34	24.9 ± 7.1	2.80 ± 1.01
1 day postoperative
mean	0.29 ± 0.25	5.1 ± 4.5	0 ± 0
variation	−0.22 ± 0.19	−19.8 ± 8.5	−2.80 ± 1.01
% of variation	−35.83 ± 46.82	−78.12 ± 19.27	−100 ± 0
1 week postoperative
mean	0.29 ± 0.30	10 ± 9.0	0.11 ± 0.46
variation	−0.21 ± 0.20	−15.2 ± 11.9	−2.73 ± 1.1
% of variation	−42.38 ± 32.46	−57.63 ± 39.34	−96.49 ± 15.29
1 month postoperative
mean	0.35 ± 0.30	13.1 ± 5.6	0.05 ± 0.22
variation	−0.16 ± 0.24	−11.9 ± 9.0	−2.75 ± 0.97
% of variation	−23.19 ± 32.16	−43.91 ± 27.24	−98.75 ± 5.59
3 months postoperative
mean	0.42 ± 0.29	11.8 ± 5.0	0.27 ± 0.59
variation	−0.12 ± 0.26	−13.1 ± 8.9	−2.44 ± 1.09
% of variation	−11.83 ± 37.27	−50.42 ± 26.80	−90.63 ± 25.62
6 months postoperative
mean	0.44 ± 0.31	13.1 ± 4.6	0.56 ± 0.86
variation	−0.02 ± 0.19	−11.9 ± 8.7	−2.28 ± 1.36
% of variation	−1.7 ± 39.96	−43.8 ± 24.08	−78.70 ± 35.95
1 year postoperative
mean	0.54 ± 0.35	14.4 ± 4.5	0.55 ± 0.94
variation	0.03 ± 0.19	−10.6 ± 8.4	−2.25 ± 1.45
% of variation	6.37 ± 45.58	−37.93 ± 25.29	−77.92 ± 38.26

In the subgroup of six patients that underwent same-site TRAB combined with phacoemulsification, the decrease in mean IOP (from 20.17 ± 5.53 mmHg to 14.2 ± 2.59 mmHg; p = 0.068) and medication use (from 1.83 ± 0.75 medications to 0.8 ± 1.10 medications; p = 0.102) was also observed, although it failed to reach statistical significance.

One year after same-site TRAB, the success rates were 25%, 66.67%, 75% and 87.5% according to criteria A, B, C and D respectively. According to criterion A, treatment failure over the follow-up period was observed in 17 eyes (70.83%) and a final IOP ≥ 12 mmHg was the cause in all the cases. According to criterion B, treatment failures over the follow-up period were observed in 8 eyes (33.33%). The most common cause was inadequate IOP control in 7 eyes (29.17%) while VA loss of two or more Snellen lines in a patient with prolonged hypotony was the cause in 1 eye (4.17%). New glaucoma surgery indications were not found over the follow-up.

Safety analysis

Postoperative complications and additional procedures are shown in Table 3. Hypotony, defined as IOP ≤ 5 mmHg, was found to be the most frequent complication (15 eyes; 62.5%) and occurred mainly in the early postoperative period. Reformation of the AC with viscoelastic was required in 3 cases (12.5%). A reduction of VA by two or more Snellen lines from baseline was noted in 1 eye (4.17%) by the last follow-up. Hyphema was present in 5 cases (20.83%) in the early postoperative period and spontaneously resolved.

Table 3.

Frequency of early and late postoperative complications and additional procedures required one year after same-site TRAB.

	No.	% eyes
Early postoperative
Hypotony	15	62.5
with maculopathy or choroidal detachment	4	16.67
with AC reformation with viscoelastic	3	12.5
with maculopathy and unrecovered vision loss	2	8.33
Hyphema	5	20.83
Wound leak	2	8.33
Filtration failure/Tenon cyst	1	4.17
Ocular hypertension due to tight scleral flap	1	4.17
Late postoperative
Prolonged hypotony	2	8.33
Filtration failure/Tenon cyst	1	4.17
Procedures
AC reformation with viscoelastic	3	12.5
Needling	3	12.5
Laser suturelysis	1	4.17

No: number; AC: anterior chamber.

Complications in the late postoperative period were present in 3 eyes (12.5%), including 2 cases (8.33%) of prolonged hypotony, that resolved spontaneously 6 months after the same-site TRAB, and 1 case (4.17%) of filtration failure due to a Tenon cyst, that required a needling procedure. Regarding postoperative procedures, AC reformation with viscoelastic (3 eyes; 12.5%) and needling (3 eyes; 12.5%) were the most frequently performed after same-site TRAB

Survival analysis

Survival curves are shown in Figure 2. Mean survival time was 10 months (CI 95% 5–15), 20 months (CI 95%: 15–26), 27 months (CI 95%: 23–31) and 29 months (CI 95%: 26–32) according to success criteria A, B, C and D respectively. The mean follow-up was 20 months (CI 95%: 16–24).

Discussion

Evidence of uncontrolled glaucoma management after failed NPDS is scarce. Alternative filtering procedures include a new NPDS^10,12 or any other filtering surgery at the same^8,9,11 or a different location.^10,12 Similar procedures have been described after TRAB failure.^9–11,13 Surgical reopening of the failed blebs could be advantageous because conjunctiva can be preserved for future surgeries, although operating in a previously used surgical field may be challenging due to excessive scarring and bleeding.^9,13

Similar to our study, Díaz-Aljaro demonstrated a significant IOP and medication use reduction in 25 patients who underwent ssDS.¹³ Mean IOP reduction was greater with same-site TRAB compared to ssDS (20.31% vs 37.9% reduction); however, mean preoperative IOP was also greater in the current study (24.90 vs 20.88 mmHg). Concerning mean medication use reduction, same-site TRAB outcomes were superior (80.36% vs. 67.27% reduction) but preoperative medication use was also greater (2.8 vs 2.2 medications). In our study, success criteria B, C and D were the same as those defined by Díaz-Aljaro. Comparing both techniques, success rates were superior with same-site TRAB (66.67% vs 36% for B; 75% vs 72% for C; 87.5% vs 80% for D).

Complications after ssDS were lower: seidel phenomena at 24 h (8%), athalamia (8%), hyphema (12%) and iris incarceration (4%). Putting all these data together, results in terms of IOP and medication use are similar or superior with same-site TRAB depending on the variables analyzed while ssDS is a safer technique.

In both studies, Ologen™ was used. It is a porous, biodegradable, collagen-glycosaminoglycan matrix implant, which directs wound healing toward tissue regeneration and away from scar formation.¹⁶ This guided wound healing would prevent postoperative scarring, which is closely related to the success of filtrating procedures. Ologen™ effectiveness has been demonstrated in filtrating techniques such as TRAB, both primarily¹⁷ and following TRAB failure.¹⁸ In the latter scenario, El-Saied reported a bleb grading improvement and a significant IOP reduction from 29.1 ± 0.9 to 12.9 ± 0.3 mmHg (55.72% reduction) at 1-year follow-up in patients with failed TRAB with MMC.¹⁸ In the present study, the subscleral placement of the Ologen™ implant augments aqueous filtration and could represent an additional advantage with lesser fibrosis and subsequently better IOP control.

Bergin compared Baerveldt implantation with a new NPDS in eyes with a failed NPDS.¹² The mean IOP reduction was significantly higher in the Baerveldt group (51.5%) than in the new NPDS group (29.2%), while there were no differences in medication use. The mean IOP reduction was lower with same-site TRAB compared to the Baerveldt group (37.9% vs 51.5%), but higher when compared to the NPDS (29.2% vs 37.9%). Same-site TRAB is performed on operated conjunctiva in contrast to the Baerveldt implantation, which consequently could affect the outcomes,¹⁹ but has the advantage of preserving more conjunctiva for future surgeries. In addition to differences between surgeries, the mean baseline IOP was lower in the new NPDS group than in our study (19.9 vs 24.9 mmHg).

Kokkoulli performed MMC-augmented needling in 108 eyes with failed NPDS.⁸ Reported complete and qualified success rates were 64% and 71% respectively at 1 year, which are similar to ours. To analyze the influence of needling in the same-site TRAB result, we compared 7 eyes (29.17%) that underwent needling after NPDS failure to those that did not (17; 70.83%), and no significant difference in terms of IOP reduction (12 vs 9.77 mmHg; p = 0.526) or use of glaucoma medication (2.14 vs 2.31 medications; p = 0.839) was found. However, we think that needling should be the first choice after NPDS bleb fibrosis, before a new surgical procedure. In 29.17% of the eyes of the study, an unsuccessful needling procedure had been performed. In the rest, needling was not considered based on the state of the conjunctiva.

Reoperation of previously failed TRAB blebs has also been reported. Nikita analyzed the same-site revision augmented with MMC in 45 eyes with a failed TRAB.¹⁴ A 43.8% and 90.48% IOP and medication use reduction were reported after one year, which are greater reductions than those obtained with same-site TRAB and may be explained by the use of high doses of MMC (0.4–0.5 mg/dL in 78% of cases) applied for 5 min and a highly proactive postoperative care. It is also remarkable that, despite all these measures, avascular blebs or late leaks were not observed, although a case of endophthalmitis was reported at 6 months. Further glaucoma reoperations were required in 19% of the cases 40.7 months after revision.

Similar to Nikita, Anand performed a revision of failed filtering surgery in 45 eyes with prior TRAB and 9 NPDS.⁹ MMC was also used but at a lower dose and less time (0.2 mg/mL for 2 to 3 min) than that reported by Nikita. An IOP reduction of 38.98% three years after surgery and a decrease of 60% in medication use at the last follow-up were reported, which are similar to ours but after a longer follow-up. A higher rate of complications than that reported after primary surgery was also noticed.

Hirunpatravonog analyzed 130 eyes that underwent same-site TRAB revision with MMC (0.2–0.4 mg/mL) for 1–3 min (based on the presumed risk factors for failure) and observed good outcomes at 5 years for patients who needed target pressures in the mid to high teens.²⁰ However, the success rate was lower in those patients who required very low IOP levels. For the most stringent criterion established by Hirunpatravonog, that corresponds with our criterion A (final IOP ≤ 12 mmHg and one of the following: IOP reduction ≥30% or a reduction of 2 medications with final IOP ≤ baseline IOP if baseline IOP ≤ 12 mmHg), the success rates were 44.6%, 29.7% and 25.8%, at the first, third and fifth years of follow-up. Applying this criterion to our patients, success rates were also lower, as only 6 of the 24 eyes (25%) achieved those target pressures after one year of follow-up. A final IOP ≤ 12 mmHg is established as the target in patients with advanced glaucoma.²¹ Therefore, we believe that patients with mild to moderate glaucoma may benefit from same-site TRAB more than those with advanced glaucoma. In addition, we think that patients with advanced glaucoma who require a lower postoperative IOP may benefit more from other glaucoma techniques.

NPDS avoiding previously failed glaucoma surgery site has also been described. Rebolleda reported an IOP and medication use reduction of 43.41% and 82.61% respectively, one year after performing NPDS with MMC in 20 eyes with failed TRAB.¹¹ Complications included a case of hyphema and a choroidal detachment. Anand demonstrated a significant IOP and medication use reduction after NPDS augmented with MMC in 82 eyes with failed glaucoma surgery and/or cataract extraction.¹⁰ A high incidence of hypotony (6.2%) was also reported.

Same-site TRAB shows lower success rates compared with primary NPDS²² or TRAB,²³ especially for more stringent criteria. Same-site TRAB is performed in eyes with previous surgeries and a repeated intervention has shown lower success rates than those achieved when performed primarily.²⁴

The TVT study has shown that eyes with previous conjunctival surgery achieved better results after tube shunt surgery than with a TRAB, although both surgeries were effective in lowering the IOP.²⁵ As a consequence, a tube shunt surgery may seem a better alternative than same-site TRAB following a failed NPDS. As we discussed before, the effect of same-site TB may not be enough for patients with advanced glaucoma who require a lower postoperative IOP and may benefit more from tube shunt surgery. However, we think that same-site TRAB is a good alternative in patients with mild to moderate glaucoma, as it spares conjunctiva for further procedures in those patients who remain uncontrolled. In addition, same-site TRAB shows lower rates of serious complications such as persistent corneal edema, suprachoroidal hemorrhage, endophthalmitis/blebitis or retinal detachment.²⁶

Regarding complications, hyphema was the most important complication (20.83%) in the early postoperative period. The incidence was higher than after NPDS in failed glaucoma surgery.^10,11 The absence of iridectomy could explain this difference. Early hypotony was common and required AC reformation in 3 cases (12.5%). The outer scleral flap after NPDS is very thin and offers minimal resistance to aqueous outflow and diathermy use may cause further thinning.⁹ These facts and the concomitant use of MMC could explain this complication. In fact, Diaz-Aljaro did not report hypotony-related complications with minimal use of MMC (0.02% for 1 min), although success rates were lower.¹³ In same-site TRAB, to avoid hypotony, 4 tight scleral sutures were used and Ologen™ was placed also at the subconjunctival level, compressing the scleral flap. Persistent hypotony was observed in 2 cases (8.33%) but only in 1 case (4.33%) determined loss of 2 or more lines of VA. Anand reported hypotony in 5 eyes (6.1%) and maculopathy with reduced VA in 2 eyes (2.4%) after NPDS and failed glaucoma surgery¹⁰ while Nikita reported transient hypotony in 5 eyes (11.1%) after revision of TRAB.¹⁴ However, malignant glaucoma and endophthalmitis were present in one case. Anand reported hypotony in 2 eyes (3.7%) after reopening the TRAB scleral flap, but also complications were present (5.6% delayed suprachoroidal hemorrhage, 9.3% delayed bleb leaks and 3.7% blebitis).⁹ Neither of these serious complications was present in our study.

In terms of hypotony-associated complications, our results are consistent with the studies that specifically addressed this issue. Rabiolo analyzed 1756 eyes that underwent NPDS and found that statistical hypotony (defined as at least one IOP value ≤ 5 mmHg over the entire follow-up) was present in 46% of the eyes. However, the hypotony was more frequently transient (33%) than chronic (13%; defined as IOP ≤ 5 mm Hg in ≥2 consecutive visits lasting >90 days or as any IOP ≤ 5 mm Hg associated with hypotony-related complications or requiring surgical intervention). Although 13% of the eyes showed chronic hypotony, the occurrence of hypotony-related complications was much less common (estimated 5-year incidence of 5.6%).²⁷ Similarly, Saeedi analyzed this complication in 753 eyes that underwent TRAB and also found that a minor proportion of the 14.9% of the eyes with late low IOP hypotony (defined as IOP ≤ 5 mmHg at or after 3 months postoperatively and all eyes that had objective signs of hypotony (choroidal detachment, shallow AC, hypotony maculopathy) and all eyes that had revision surgery for low IOP, regardless of time after surgery) suffered hypotony-related complications or required surgical intervention (8% and 5% of the eyes respectively).²⁸ In the same way, 62.5% of the eyes in our study had statistical hypotony but it was not associated with complications or required further interventions in most of the cases. However, a greater proportion of eyes in our study (12.5%) required AC reformation with viscoelastic. As we discussed before, the minimal resistance to aqueous outflow resultant from a very thin outer scleral flap after NPDS and further thinning subsequent to diathermy may explain this difference.⁹ In addition, Saeedi described an interesting association between younger age and postoperative AC reformation after TRAB and pointed out that surgeons may be more prone to perform this procedure in younger patients because of the severity of their symptoms or in the expectation that surgery would be more likely to benefit them.²⁸ As a consequence, we think that some variability between surgeons in the decision to perform an AC reformation may exist. It is possible that some surgeons are more likely to perform this procedure, or perform it earlier, and this variability in clinical practice may also explain in part the different number of procedures between studies.

Another safety indicator is the number of subsequent procedures. Diaz-Aljaro did not quantify any subsequent procedure¹³ while Anand reported a high rate,⁹ including needling in 23 eyes (42.5%) and further glaucoma surgery in 5 eyes (9.3%). In Nikita study, 9 eyes (19%) required further glaucoma surgery and 9 eyes (19%) cyclodiode laser.¹⁴ In addition, dexamethasone or 5-fluorouracil subconjunctival injections were administered in 35 eyes (77.78%) within 8 weeks from surgery. In the present study, 5 eyes (20.83%) required 7 procedures. This may mean that same-site TRAB requires less subsequent procedures than other interventions based on the revision of failed blebs. However, in our study, the follow-up is limited to one year while in the aforementioned studies it is longer.

Differences between studies, absence of comparative studies and different surgical approaches limit the establishment of evidence-based recommendations of first line surgery following NPDS failure. The absence of a comparative group, the relatively small sample size, the short follow-up period, the inclusion of both eyes of two patients and the retrospective nature are the main limitations of this study. The heterogeneity of the sample is also a limitation, as patients with previous glaucoma surgery or a combined phacoemulsification procedure are included. Although a heterogeneous sample is a known potential source of confusion that may limit the conclusions, we find that it is common in other published studies on this topic.^9–11,13,14 A possible explanation is that reintervention after a failed filtering surgery is not such a frequent procedure and gathering a considerable sample would be difficult if excluding these patients. It is also noticeable that, when the influence of these factors has been assessed, prior cataract extraction or the number of previous glaucoma surgeries have not shown a significant effect on the survival curve of the surgical revision after a failed filtering surgery.^9,14

In conclusion, same-site TRAB augmented with MMC and Ologen™ is an effective alternative in patients with previous NPDS failure. Postoperative hypotony occurs in a high percentage of cases in the early postoperative period but it is reversible in most cases. No serious complications were observed. Further, larger and comparative studies are necessary to address the preferred filtering technique after NPDS failure.

Footnotes

Declaration of conflicting interests

The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Funding

The author(s) received no financial support for the research, authorship, and/or publication of this article.

ORCID iDs

FJ Muñoz-Negrete

V Aguado-Casanova

FJ Huelin

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