Evaluating the outcomes of inferonasal ahmed valve implantation using the double scleral tunnel technique in refractory glaucoma

Abstract

Background

To evaluate the efficacy and safety of inferonasal quadrant (IN) Ahmed Valve implantation (AVI) using the double scleral tunnel technique in patients who had previously failed glaucoma surgery.

Methods

This retrospective comparative study included data from 69 patients diagnosed with refractory glaucoma who were followed in a tertiary referral hospital. The IN-AVI group included 35 patients who underwent IN-AVI after failed trabeculectomy or superotemporal quadrant (ST) AVI, and the ST-AVI group included 34 patients who underwent primary ST-AVI. The primary outcome was to analyse the surgical success rate, the secondary outcome was to compare the intraocular pressure (IOP) reduction in the IN-AVI and ST-AVI groups at 1-year postoperatively.

Results

Significant reduction in IOP was observed after IN-AVI at 1-year postoperatively (p < 0.001). The overall success rate was 88.6%. IN-AVI after failed trabeculectomy didn’t differ from primary ST-AVI in terms of IOP reduction. IN-AVI after failed ST-AVI showed a lower IOP reduction compared to primary ST-AVI (p = 0.003). No tube exposure was observed at 1-year postoperatively using the double scleral tunnel technique.

Conclusions

In patients with refractory glaucoma, IN-AVI after failed trabeculectomy was as effective as the primary ST-AVI. Although IN-AVI after failed ST-AVI was effective in reducing IOP, it was significantly less effective than the primary ST-AVI. The prior failure of a trabeculectomy had no impact on the success of AVI. Conversely, a second AVI was less efficacious than the primary AVI.

Introduction

Refractory glaucoma is a condition of poorly controlled intraocular pressure (IOP) with progressive optic nerve damage and visual field loss, despite the use of maximum-tolerated antiglaucoma medication and/or previous glaucoma surgery. Patients with a high risk of failure of conventional glaucoma surgery, such as neovascular glaucoma, traumatic glaucoma, uveitic glaucoma, silicone glaucoma, or failed filtering/shunting glaucoma surgery, are considered to have refractory glaucoma [1, 2].

Surgical intervention is indicated when IOP cannot be controlled and/or glaucoma continues to progress despite maximally tolerated medical treatment. Despite advances in surgical treatment for glaucoma, trabeculectomy and glaucoma drainage device (GDD) implantation remain the most common surgical procedures [1]. The evidence from long-term studies in the literature indicates that both procedures are effective in controlling IOP over an extended period of time [3, 4]. Excessive fibrosis is the most common cause of failure in both procedures [5, 6]. Coulon et al. found no significant difference in the failure rate between trabeculectomy and Ahmed valve implantation (AVI) surgery at five years postoperatively [7].

After failure of incisional glaucoma surgery, there is no clear consensus on which surgery should be performed. Several studies have reported different results regarding the success, safety, and reoperation rates of surgical options that may be preferred after previously failed glaucoma surgery [1, 8,9,10].

The Ahmed Glaucoma Valve (New World Medical, Inc., Rancho Cucamonga, CA, USA) is an implant device designed for IOP control, particularly in patients with refractory glaucoma. Despite the recommendation by manufacturers to implement the device within the upper temporal quadrant, in cases involving scarring of the upper conjunctiva due to prior surgeries, thinning of the upper conjunctiva due to antimetabolite utilisation or silicone oil in the upper subconjunctival area, even in the absence of scarring, it may necessitate the implantation of the device from the spared other quadrants. It was observed that the occurrence of diplopia seems to be more frequent in cases where the implants are placed superonasally, a phenomenon that may be attributed to the presence of the superior oblique muscle complex [11]. Irrespective of the dimensions of the implant employed, instances of acquired Brown syndrome have been documented, consequent to the constriction of the superior oblique tendon, either due to filtering blebs or fibrotic reactions induced by the implant positioned in the superonasal quadrant [12]. On the other hand, implantation in the inferotemporal quadrant has been associated with an unfavourable cosmetic outcome due to the formation of a significant filtering bleb, which has been observed to distort the lower lid and cause a bulge in the area. Secondly, the inferior oblique muscle complex is located in the inferotemporal quadrant; studies have indicated that it can elevate the risk of diplopia, similar to the effect observed with superior oblique quadrant influence on superonasal implants [11]. Taking these into consideration, it is suggested that the second preferred placement of the device should be considered in the inferonasal quadrant [13].

The primary objective of this study was to assess the efficacy and safety of inferonasal quadrant (IN) AVI using the double scleral tunnel technique in patients who had previously undergone failed glaucoma surgery. The secondary outcome of this study was to examine whether IN-AVI following a previously failed glaucoma surgery (trabeculectomy or superotemporal (ST) -AVI) is as successful as primary ST-AVI.

Methods

This retrospective and comparative case series study included data from 69 eyes of 69 patients with refractory glaucoma who underwent AVI at a single center between August 2021 and January 2023, and were followed up for 1 year postoperatively. This study was approved by the University’s Ethical Committee (DNR. E1 - 23–4414), and adhered to the tenets of the Declaration of Helsinki.

All patients underwent comprehensive ophthalmological assessment, which included best-corrected visual acuity evaluation, slit-lamp examination, gonioscopy, dilated fundus examination, and optic disc evaluation. IOP was measured three times at each visit using Goldmann applanation tonometry. The mean value was recorded, and preoperative baseline data were established by accepting the measurements taken during the last visit before surgery.

Postoperatively, data regarding IOP and number of medications in the study group were collected at 1, 3, 6, and 12 months. Side effects of the surgery were recorded at 1 day, 1 week and 1, 3, 6 and 12 months postoperatively. Patients who were unable to attend the scheduled control examination during the 12-month follow-up period were excluded from this study. The reduction in IOP and the change in the number of medications used in the IN-AVI and ST-AVI groups were compared in the first postoperative year.

Patient selection

The IN-AVI group comprised 35 patients with refractory glaucoma who had previously undergone trabeculectomy or ST-AVI and had an IOP > 21 mmHg despite the administration of maximum tolerated medical anti-glaucomatous therapy. The IN-AVI group included patients who underwent inferonasal seton implantation either because the superior temporal conjunctiva was compromised by previous trauma, surgery, or antimetabolite use, or because it was already occupied by a prior seton implantation in the superotemporal quadrant. The ST-AVI group comprised 34 patients diagnosed with refractory glaucoma who underwent a primary ST-AVI procedure due to IOP > 21 mmHg, despite the use of maximum tolerated medical therapy.

The diagnosis of glaucoma was confirmed based on the presence of glaucomatous optic neuropathy, retinal nerve fiber layer defects detected by Swept Source optical coherence tomography (Topcon Healthcare, USA), and visual field defects identified in the 24–2 central perimetry by Humphrey Field Analyzer (model 750; Carl Zeiss Meditec, Inc, USA). Patients in both the IN-AVI group and the ST-AVI group were pseudophakic. Subjects who underwent AVI combined with phacoemulsification and phakic AVI were excluded from the study. Patients with primary open-angle glaucoma, primary angle-closure glaucoma, or congenital or juvenile open-angle glaucoma were also excluded.

Surgical technique

The surgical procedure involved implantation of an Ahmed valve via a double-scleral tunnel technique. Under regional or general anesthesia, a traction suture was passed through the cornea. This was followed by broad conjunctival fornix-based peritomy in the selected quadrant (superotemporal or inferonasal). In a manner analogous to that employed in the patients who underwent trabeculectomy, mitomycin C (MMC) was administered to patients who underwent Ahmed valve implantation. Sponges soaked with 0.2 mg/mL MMC were applied for a period of two minutes to the scleral bed beneath the conjunctiva and Tenon's capsule, followed by irrigation with a balanced salt solution. The plate was then fixed to the sclera 9–10 mm away from the limbus. Two scleral tunnels were created approximately 4 and 8 mm from the limbus using a crescent blade. These two tunnels were subsequently connected to form a single, longer tunnel. The tube was then placed almost entirely within the sclera. A 23-gauge needle tract was used to gain access to the anterior chamber through the limbus. Once the needle reached the surgical limbus, it was directed downwards to enter the anterior chamber. The distal end of the tube was cut obliquely with the bevel facing upward to prevent obstruction of the iris by a length of approximately 2–3 mm in the anterior chamber. The conjunctiva and Tenon’s capsule were repositioned and sutured at the limbus. Topical antibiotics were prescribed four times a day for one week, and topical steroids were prescribed four to eight times a day for six to eight weeks and tapered off.

Study outcome measures

The primary outcome of this study was to analyze the changes in IOP measurements, the number of medications used in the postoperative period, and the surgical success rate in the first postoperative year. Complete surgical success was defined as IOP less than 18 mmHg without the use of any anti-glaucomatous medication, and qualified surgical success was defined as IOP less than 18 mmHg with the use of antiglaucomatous medication at 1-year after AVI.

The secondary outcome of this study was to compare IOP reduction and the change in the number of medications used in the IN-AVI and ST-AVI groups at one year postoperatively.

In subgroup analyses, patients in the IN-AVI group were divided according to their previous failed surgery (trabeculectomy or ST-AVI), and the changes in IOP measurements and number of medications used in the postoperative period were compared with those in the ST-AVI group.

The active ingredients were considered when assessing the number of medications used by the patients. An IOP spike was defined as an IOP ≥ 21 mmHg within three months of surgery.

Statistical analyses

In descriptive statistics for continuous data, the mean, standard deviation, median, 25 th- 75 th (interquartile range), and minimum and maximum values were presented as numbers and percentages in discrete data. The suitability of continuously recorded data for a normal distribution was assessed using the Shapiro–Wilk test.

Friedman ANOVA was employed to assess the IOP values and number of medications used at four time points: preoperatively, 3 months postoperatively, 6 months postoperatively, and 12 months postoperatively. To ascertain which follow-up times caused the difference, Friedman's Multiple Comparison Test was employed for the purpose of statistical analysis.

The Mann–Whitney U test was used to compare the preoperative and postoperative 12-month IOP values and the number of medications used in the study and control groups.

To assess IOP reduction during the 12-month postoperative follow-up period, the Mann–Whitney U test was used to compare the IN-AVI and ST-AVI groups. The Chi-square test was used in the cross-tabulation of nominal variables for group comparisons. The IBM SPSS version 20 (Chicago, IL, USA) program was employed in the evaluations, with p < 0.05 accepted as the p-value limit for statistical significance.

Results

The study comprised 69 patients, divided into two groups. The IN-AVI group (n = 35) included those who had previously undergone failed glaucoma surgery (trabeculectomy or ST-AVI) and subsequently underwent IN-AVI using the double scleral tunnel technique. In the IN-AVI group, 22 patients had a history of failed trabeculectomy, while 13 had a history of failed ST-AVI. The ST-AVI group (n = 34) consisted of refractory glaucoma patients with no history of glaucoma surgery who underwent primary implantation of Ahmed valve in the ST quadrant. Demographic and baseline characteristics of the patients are shown in Table 1.

Table 1 Comparative analysis of the characteristics of patients in the IN-AVI and ST-AVI groups

Table 2 provides an overview of the distribution of patients in the study and control groups according to glaucoma subtype. The most common refractory glaucoma subtype in both study and control groups was neovascular glaucoma.

Table 2 Subtypes of glaucoma in the IN-AVI and ST-AVI groups

A statistically significant difference was observed between the preoperative, postoperative 3rd month, postoperative 6 th month and postoperative 12 th month IOP values (p < 0.001). The results demonstrated that postoperative IOP values were significantly lower than preoperative values (Fig. 1). In addition, the number of medications used at 3, 6, and 12 months postoperatively was significantly lower than that preoperatively (p < 0.001) (Fig. 2).

Fig. 1

IOP measurements preoperatively, at postoperative 3rd,6 th and 12 th month in the IN-AVI group

Fig. 2

The number of medications used preoperatively, at postoperative 3rd,6 th and 12 th month in the IN-AVI group

In the IN-AVI group, both the previously failed trabeculectomy and failed ST-AVI subgroups demonstrated a statistically significant reduction in IOP at 3, 6, and 12 months postoperatively compared to the preoperative period (p < 0.001) (Table 3). IN-AVI following a failed trabeculectomy resulted in a more significant reduction in IOP compared to IN-AVI following a failed ST-AVI (p = 0.045) (Fig. 3).

Table 3 Comparison of Preoperative, Postoperative 3rd month, Postoperative 6 th month and Postoperative 12 th month IOP measurements of patients who underwent IN AVI according to previous failed surgery

Fig. 3

Comparison of IOP reduction according to the previously failed glaucoma surgery procedure in the IN-AVI group

Patients who were treated with IN-AVI following the failure of ST-AVI exhibited a diminished reduction in IOP at the conclusion of the first year in comparison to those who underwent primary ST-AVI (p = 0.003) (Table 4). No statistically significant difference was observed in terms of IOP change at the end of the 1 st postoperative year in patients who underwent IN-AVI after previously failed trabeculectomy surgery compared with the patients who underwent primary ST-AVI (p > 0.05) (Table 5). By the end of the first year, there were no significant differences between the subgroups and the control group in terms of changes in the number of medications utilized (p > 0.05) (Table 4,5).

Table 4 Comparison of IOP and medication reduction at postoperative 12 th month in IN-AVI after failed ST-AVI subgroup and primary ST-AVI group

Table 5 Comparison of IOP and medication reduction at postoperative 12 th month in IN-AVI after failed trabeculectomy subgroup and primary ST-AVI group

The overall success rate was 88.6% in patients who underwent IN-AVI after a failed glaucoma surgery. At 1 year follow-up, a complete success rate was achieved in 34.3% and a qualified success rate was achieved in 54.3% of the patients who underwent IN-AVI after a previously failed glaucoma surgery.

After IN-AVI, the most common complication in the early postoperative period was a shallow anterior chamber, which resolved within a few weeks. No complications, such as endophthalmitis, corneal decompensation, diplopia, plate migration, tube exposure, or occlusion, were observed during the 1-year postoperative period following IN-AVI. There was no difference in the rate of complications between the IN-AVI and ST-AVI groups (Table 6) (p > 0.05). Following a one-year follow-up period, needling in conjunction with MMC was conducted on four patients in the IN-AVI group and three patients in the ST-AVI group.

Table 6 Comparison of the complication rates in IN-AVI and ST-AVI groups

Discussion

The frequency of GDD implantation has increased significantly over the past three decades [14]. The Ahmed Glaucoma Valve is recommended to be placed in the superotemporal quadrant. GDD implantation is performed from other quadrants when implantation from the superotemporal quadrant cannot be performed for reasons such as conjunctival scarring, previous surgeries, and thinning of the sclera [15]. In this study, inferonasal quadrant GDD implantation was performed on patients in whom superotemporal quadrant implantation was not possible due to previous trauma, surgeries and/or antimetabolite use.

In a study that compared the primary implantation of Ahmed valve in the superior quadrant (predominantly superotemporal quadrant) and inferior quadrant (predominantly inferotemporal quadrant), no statistically significant difference was found between the two groups in terms of IOP control [16].

Martino et al. [17] also did not find any difference between the overall success rates of the first GDD implantation performed on the superior and inferior limbus. There are limited data on the outcomes of GDD surgery after failed trabeculectomy compared to eyes that underwent GDD as the primary glaucoma surgery. In eyes with previous glaucoma surgery, a higher success rate was observed in the Baerveldt tube shunt group than in the trabeculectomy group, with MMC, during a five-year follow-up period, according to the TVT trial [5]. In our study, IOP and number of medications used were significantly reduced at 3, 6, and 12 months after inferonasal AVI in patients who had previously failed trabeculectomy or shunt surgery (p < 0.001).

Although studies have investigated the results of a second AVI in the other quadrants after a failed ST quadrant AVI [18, 19], IN quadrant AVI is the least documented in the literature. In contrast, a literature review identified a study by Francis et al. [20] that examined the results of BVI in the IN quadrant. The study reported an overall success rate of 76.2% (IOP < 18 mmHg with or without medication) following a second BVI in the IN quadrant at 12 months postoperatively [20].

In our study, at the 12-month postoperative follow-up visit, 88.6% of patients achieved an IOP of 18 mmHg or less, with or without any anti-glaucomatous medication, after IN-AVI in patients with refractory glaucoma.

In a study by Nilforushan et al., the second AVI surgery performed in the superonasal and inferotemporal quadrants after previously failed AVI surgery achieved an IOP < 21 mmHg in 80% of patients in the first postoperative year, with or without medication [21]. In our study, at the end of the first postoperative year, with or without any anti-glaucomatous medication, 62.8% of patients achieved an IOP of 15 mmHg or less after IN-AVI in patients with refractory glaucoma.

In a meta-analysis by Yoon [22], in which the authors evaluated the results of nine previous studies, there was a tendency for the second GDIS to fail earlier. In the present study, subgroup analyses demonstrated that at the 1-year postoperative period, a second AVI resulted in significantly lower IOP reduction than the first AVI. In cases where single-digit IOP measurements are required in patients with a history of previously failed AVI, it may be advisable to consider alternative valveless GDD implantation or cyclodestructive surgery. In this study, IOP reduction after IN-AVI was significantly greater in patients with a previous trabeculectomy than in those with a previous shunt surgery. According to the literature, the success of GDD implantation is affected by the patient's fibrotic response around the plate [23] and the extent of cytokine activity in the aqueous humor and Tenon's capsule [24]. In the IN-AVI group, subjects who had previously failed ST-AVI had prior exposure to an Ahmed valve and exhibited a reaction to it. It is possible that a second AVI could provoke a stronger fibrotic and immune response to the Ahmed valve than the initial one. Consequently, the reduction in IOP may be less pronounced in these cases compared to eyes that previously failed a trabeculectomy, which is an implantless glaucoma surgery.

The findings of this study indicated that there was no statistically significant difference in IOP reduction between the IN-AVI in patients who had previously undergone failed trabeculectomy and the ST-AVI group. Similarly, Dawson et al. found that previous failure of filtration surgery did not appear to affect the outcome of subsequent GDD surgery [1].

In subgroup analyses, IN-AVI after failed trabeculectomy did not differ significantly from primary ST-AVI in terms of IOP reduction, whereas IN-AVI after failed ST-AVI showed a lower IOP reduction. These data suggest that the quadrant of AVI does not affect the IOP reduction. Therefore, it may be preferable to determine the type of subsequent surgery on the basis of which surgical procedure has failed.

One of the main concerns with inferior quadrant GDD implantation is its safety. Levinson et al. reported that the highest implant exposure was in the inferior nasal quadrant [25]. In a study investigating the risk of exposure and infection after GDD implantation, implant location was a significant risk factor for exposure and infection in patients in whom the implant tube was covered with a patch graft [13]. It has been postulated that inferiorly placed devices may be at an elevated risk of exposure owing to mechanical disruption of the patch graft from the lower lid [26]. In our study, no tube exposure or intraocular infection was observed in any patient who underwent IN-AVI during the one-year follow-up period.

No significant difference in complication rates was detected between the IN-AVI and ST-AVI groups, suggesting that IN-AVI is as safe as ST-AVI. After an IN-AVI surgery, the most common complication in the early postoperative period was a shallow anterior chamber that resolved within a few weeks. There were no complications, including endophthalmitis, corneal decompensation, diplopia, plate migration, tube exposure, occlusion, or any complications that required surgical intervention during the one-year postoperative period following IN-AVI.

Inferior implantation of Ahmed valve may also lead to higher rates of large disfiguring encapsulated hemorrhages, cosmetically unacceptable exposure of the scleral patch graft, or a lower lid bulge [26]. In a previous study, Fahy et al. demonstrated that the double scleral tunnel technique may reduce the risk of postoperative tube exposure by reducing micromovements of the GDD tube [27]. A notable disadvantage of the IN-AVI approach, utilising the scleral tunnel technique, is the relative complexity involved in accessing the surgical area, in comparison to other quadrants, particularly with regard to the creation of the tunnel. In our study, tube exposure was not observed during the one-year period following IN-AVI using the double scleral tunnel technique.

It has been hypothesised that the efficacy of GDD implantation may be influenced by the number of prior intraocular surgeries [28]. Whilst comparing a secondary procedure with a primary device implantation is likely to disadvantage the former group, the results of this study provide substantial evidence to support the decision to implant the IN-AVI after failed glaucoma surgery.

The retrospective design is a limitation of this study. To the best of our knowledge, this is the first study with the largest number of patients in the literature to analyse the results of IN-AVI using the scleral tunnel technique after a failed glaucoma surgery.

Based on this study, it can be concluded that IN-AVI is an effective surgical option in the early and medium term after previously failed glaucoma surgery. In patients with refractory glaucoma, IN-AVI after failed trabeculectomy was as effective as the primary ST-AVI. Although IN-AVI after failed ST-AVI was effective in reducing IOP, it was significantly less effective than the primary ST-AVI in refractory glaucoma. Therefore, if single-digit IOP values are required in patients with a previously failed AVI, valveless GDD implantation or cyclodestructive surgery may be a better option. Although previous studies have reported safety concerns regarding inferior quadrant GDD implantation, no complications of exposure or intraocular infection were observed in any of our patients who underwent IN-AVI using the scleral tunnel technique during the 1-year postoperative period. This study demonstrated that IN-AVI following failed glaucoma surgery is an effective method for reducing IOP.