Most previous studies defined successful TLE or EXP as a postoperative IOP of 18 mmHg or less. However, the Advanced Glaucoma Intervention Study reported that visual field impairment progressed unless the IOP was maintained at < 12.3 mmHg [8], and subjects with NTG often have IOP values < 18 mmHg. Therefore, in this study, we set the target IOP at several lower levels (criteria B and C).
Filtering surgery, including TLE, is a common and standard modality for patients with long-standing glaucoma. While we expected EXP to reduce IOP as effectively as TLE, based on previous studies [3–4, 12], an equivalent efficacy has not been demonstrated for lower target IOP ranges. As the baseline IOP of some patients was in the normal range under maximum medical therapy, some studies have used the percentage reduction from baseline as an outcome metric in addition to absolute IOP levels. However, this criterion is not applicable in all situations. In the Japanese population, NTG accounts for the majority of glaucoma cases [10]. Low preoperative IOP as in NTG makes it difficult to achieve a 20% reduction from baseline after filtering surgery without complications [13–14]. Therefore, only patients with IOP ≥ 15 mmHg were included in this study.
Several previous prospective studies have compared the success rate of TLE to EXP both with and without the use of glaucoma medications. Gonzalez-Rodriguez et al [4] defined surgical success as 5 ≤ IOP ≤ 18 (criterion A in our study) and a 20% reduction from baseline, and reported success rates of 59% and 76% for EXP and TLE groups, respectively, at 24 months and 52% and 61%, respectively, at 36 months. In accord with our results using criterion A, these rates did not differ between procedures.
Most previous studies have found no difference in the number of glaucoma medications required by patients following EXP or TLE [4, 5, 15–17], while a few have reported that the EXP group required fewer glaucoma medications [3, 18] and one that patients required more medications following Ex-PRESS implantation [19]. In the current study, we found no significant difference in the number of glaucoma medications required before or after surgery. However, the EXP group required more glaucoma medications than the TLE group post surgery, and the group difference in the number of eye drops required increased gradually during follow-up. Thus, it is likely that the EXP group will eventually require a significantly greater number or significantly higher doses of glaucoma medications.
We found little difference in complication rates following EXP or TLE. One patient in the TLE group developed cataract, which resulted in loss of VA during the observation period, while there were no cases of cataract progression in the EXP group. Similarly, Beltran-Agullo and colleagues reported that cataract progression was more frequent following TLE than EXP [20], potentially because EXP does not require peripheral iridectomy and thus carries a lower risk of hypotony. Aqueous flare elevation may occur during or following filtration surgery due to disruption of the blood–aqueous barrier, and flare severity increases with inflammatory activity in the anterior segment [21]. One case study reported substantial flare on the first day after EXP that subsided by the third day [22], while another reported elevated flare at 4 weeks after TLE [23]. The more sustained flare after TLE may also result from iridectomy. Further, the reduced inflammation following EXP may prevent cataract progression. Moreover, Arimura and colleagues [16] reported a significantly greater total number of complications following TLE than following EXP. However, other studies have reported similar incidences of most early complications with the exception of hyphema [24]. In the current study as well, there were no significant differences in early and late postoperative complications between treatment groups. No late complications due to hypotony, such as hypotony maculopathy and choroidal detachment, were observed in the EXP group. However, one case in the TLE group exhibited choroidal detachment related to over filtration and low IOP. We assume that this is because EXP surgery creates a constant aqueous outflow route. From this, we expect that EXP is more suitable for patients at risk for complications related to low IOP. For example, young patients with long axial length tend to develop hypotony maculopathy after TLE [25], which could lead to a reduction in VA.
A Cox regression model identified the number of glaucoma medications before surgery as a risk factor for surgical failure in the TLE group, consistent with previous studies [26–27] and suggesting that preservatives of glaucoma medication increase the risk of TLE failure [28]. Postoperative subconjunctival fibrosis after ophthalmic surgery results in increased numbers of conjunctival fibroblasts and inflammatory cells [29], and preservatives will further increase the number of conjunctival fibroblasts and macrophages while reducing the number of conjunctival goblet cells [28]. These alterations lead to production of predisposition to heal the fistula drainage, resulting in uncontrolled IOP [26, 28]. Since the role of the conjunctiva is the same in TLE and EXP, it can be expected that glaucoma medication will reduce the surgical success of EXP through similar mechanisms. However, the number of glaucoma medications was not a risk factor for EXP failure in this study. EXP does not require iridectomy and leads to less bleeding and inflammatory cell infiltration. As a result, fibrosis of the conjunctiva may be prevented after EXP, reducing the risk of surgical failure.
One limitation of this study is the group imbalance and relatively small number of patients because we exclude patients with preoperative IOP < 15 mmHg after randomization. We followed patients for 3 years in this study. The number of dropout patients increased with long-term follow-up, which is another limitation of this study. As glaucoma requires lifelong treatment, longer-term clinical follow is required.
In conclusion, no differences in surgical success, IOP, VA, and failure rates were noted between the EXP and TLE groups in this study. We also found that the number of glaucoma medications was a risk factor for surgical failure in the TLE group but not the EXP group.