Circumferential (360°) trabeculotomy for steroid-induced glaucoma in adults

Forty-six eyes of 35 patients were included (mean age 46.6 ± 15.6 years, 51% male). Surgeries were performed between January 2017 and June 2021, in Amsterdam by LJR and in Nijmegen by CAE.

The conditions necessitating steroids were related to the cornea, uveitis, diabetic macular edema, persistent edema after vitreoretinal surgery, and systemic illness. SIG caused by topical, intravitreal, subtenon, and systemic steroids were included. The first high IOP (> 21 mm Hg) was noted 8.3 ± 10.6 (mean ± SD) months before surgery (median 3.5, range 0–40 months, n = 44). The first very high IOP (> 30 mm Hg) was noted 6.1 ± 10.6 (mean ± SD) months before surgery (median 1.0, range 0–40, n = 41). Mean IOP before surgery was 30.8 ± 8.3 mm Hg. (Table 1).

Figure 1 shows the intraocular pressure before and after surgery. The median pressure was lower than 15 mm Hg throughout the follow-up period, and IOPs above 20 mm Hg were only found in the first month and in one patient after 3–12 months. This patient went on to receiving a GDD. The mean IOP was 30.8 ± 8.3 mm Hg before surgery, 13.3 ± 4.5 mm Hg after 3–12 months, and 11.2 ± 2.6 mm Hg after 1–2 years. Results after more than 2 years were similar, though the number of eyes was smaller.

Right before surgery, the number of PLMs was high: several patients used apraclonidine and acetazolamide above the regular glaucoma medication. The mean number of PLMs before surgery was 3.8 ± 1.0 mm Hg. The mean number of PLMs was 1.0 ± 1.3 Hg after 1–3 months, 1.0 ± 1.4 Hg after 3–12 months, and 0.9 ± 1.3 mm after 1–2 years. Results after more than 2 years were similar, though the number of eyes was smaller.

Figure 2 shows the Kaplan–Meier curve for IOP control with and without medication [8]. After surgery, except for one case, IOPs were lower than 21 mm Hg with medication. (Estimated survival 98 ± 2%, mean ± standard error.) Most cases needed medication to control their pressure after surgery. (Estimated probability of not using IOP-lowering medication: 39 ± 11%.) The one case with uncontrolled pressures was later well controlled after implantation of a GDD. Estimated 80 ± 8% of cases had an IOP (with medication) below 18 mm Hg, and estimated 61 ± 12% had an IOP (with medication) below 15 mm Hg.

By means of a Cox proportional hazard model, we investigated the role of several factors determining successful outcome. As dependent variable, we choose “IOP < 21 mm Hg without medication.” This variable provided better contrast than “IOP < 21 mm Hg” since the majority of eyes fulfilled the latter criterion. We investigated the factors such as diagnosis, mean IOP 1 month before surgery, hospital, and application of steroid (subtenon or intravitreal/topical/systemic). In a multivariate model and in successive univariate models, none of these factors was significant.

All eyes received topical steroids during at least 4 weeks after surgery. Due to the underlying condition, in many cases, steroids needed to be continued after surgery. At 3–12 months, 28 of 39 eyes received some form of steroid therapy. We did not find a relation between discontinuation of steroids and success of surgery, indicating that the steroid response was no longer present. Ten eyes continued to receive either subtenon or intravitreal steroids. In all eyes, the IOP remained low and not significantly different from the eyes receiving none or only topical steroids.

Complications consisted of transient hyphema (n = 14), postoperative hypotony (IOP below 5 mm Hg, n = 3), and postoperative hypertony (IOP above 21 mm Hg within 1 week after surgery, n = 6). All of those resolved within several days to weeks. For postoperative hypertony with hyphema, in two eyes, an anterior washout was performed and in one eye a paracentesis. In one patient, during the pulling of the catheter, a Descemet detachment was created. Upon noticing this, the pulling was stopped, and the catheter was repositioned after which the procedure could be continued. At the end of the surgery, a large air bubble was left in the anterior chamber. After surgery, there was a Descemet detachment over the lower cornea, which resolved spontaneously within 2 weeks (Fig. 3).

Our findings are in accordance with other studies. Honjo et al. [9] performed TO in 14 eyes of seven patients with SIG. Initial pressures were high (34.6 ± 8.4 mm Hg); six patients were not able to stop their steroids. Their success rate was 83.6% (pressure lower than 21 mm Hg with medication) after 5 years. Iwao et al. [3], in a multicenter study, demonstrated that (120°) TO for SIG was much more successful than for POAG (73.5% vs 51.7% success (IOP < 22 mm Hg with or without medication) after 5 years). For SIG, TO was just as successful (73.5% vs 74.5% IOP < 22 mm Hg after 5 years) or less successful (51.7% vs 71.6% IOP < 19 mm Hg after 5 years) than TE. Complications were less in the TO than TE groups. Hence, TO was better suited for SIG than for POAG and, although successful, IOPs are somewhat higher after TO than after TE for SIG.

Other than our study, these studies did not distinguish between complete and qualified success and did not have a cut-off value for the duration of existence of SIG, as was commented on the paper by Iwao et al. [10, 11]. We speculate that our higher success rate (98% success if defined as IOP < 22 with or without medication) is due to our strict inclusion criterion: only SIG with limited duration of existence was included.

GATT was performed in 13 eyes with SIG, all of which had to continue using steroids after surgery [12]. Half of the patients had uveitis. The procedure was successful in all eyes with a mean IOP at 24 months of 10.5 mm Hg and an average number of medications of less than 1. Just as in our study, pressures and number of medications before surgery were high.

A higher preoperative IOP seems a poor prognostic factor for TO in POAG and exfoliative glaucoma [13], but not for TO in SIG [3]. Postoperative pressure spikes are frequently observed and do not hinder long-term success of the procedure [14].

Trabectome was successful for 20 eyes SIG [15], resulting in an IOP reduction from 33.8 to 15.0 mm Hg on average at 12 months after surgery. In a comparative study [16], it was reported that Trabectome-assisted goniotomy resulted in more pressure reduction in SIG than in POAG although a 12-month survival rate was similar at 85%.

Bao et al. [4], in a retrospective study, showed that TO had a lesser long-term success than TE for POAG in 25 and 20 eyes, respectively. The mean follow-up was 8 years.

Recently, several authors reported about the efficacy of SLT for SIG. Zhou et al. [17] performed SLT in 29 eyes with SIG, with a mean baseline pressure of 27.6 mm Hg. They found 54% failure after 2 years (less than 20% IOP reduction more than 3 weeks after the SLT). This was similar to a subgroup of POAG eyes with comparable baseline IOPs. Generally, the IOP decreased 3–8 weeks after the SLT treatment. The rate of hypotensive medication reduced from 3.5 at baseline to 1.9 by 18 months AlObaida [18], applying SLT in 25 eyes with SIG, found an IOP reduction from 23.7 to 14.4 mm Hg on average 19 months after the treatment (39% reduction). This is similar to the pressure reduction found for early POAG and ocular hypertension in the LIGHT trial [19]. Xiao et al. reported a gradual IOP reduction from 30.6 to 15.1 mm Hg (48%) at 12 months after the treatment in 16 eyes with SIG and quiescent uveitis. Four patients went on to surgery, two of which had anterior synechiae, potentially sequalae of an SLT. Maleki et al. [20] applied SLT in 15 eyes with SIG after a fluocinolone acetonide implant for uveitis. Seven eyes reached target with a pressure of 15.14 mm Hg (50.4% reduction) at 12 months after the treatment. Eight eyes failed after treatment within 12 months. The aforementioned studies demonstrate the effectiveness of SLT for SIG. Especially in SIG patients where the IOP is not extremely high and/or there is time to wait for the effect of SLT (on average 6 weeks), SLT might be an elegant first step in the attempt to lower the IOP in SIG. However, when the IOP is too high, one may directly choose for surgery, as we did with our patients.

The primary regulation of IOP resides in the outflow system [21, 22]. Removal of TM resulted in a reduction of 75% in outflow resistance in normal eyes and removal of abnormal resistance in glaucomatous eyes [22]. Schlemm’s canal lumen decreases at higher levels of IOP [23]. Remarkably, removal of the outer wall also resulted in a 75% reduction of outflow resistance [24].

Kagemann et al. [25] showed in an in vitro OCT study that cross-sectional Schlemm’s canal surface was smaller in glaucoma patients than in normal controls. Increase of episcleral venous pressure results in increase of Schlemm’s canal diameter [26]. Apposition of the TM with Schlemm’s canal outer wall results in an increase in outflow resistance, a mechanism that can be eliminated by keeping the TM away from Schlemm’s canal outer wall [27] or by TO [24]. Outflow resistance is higher at high intraocular pressures than at low pressures, presumably through collapse of Schlemm’s canal and entrance of the TM in the collector channel entrances [28].

Contractile elements within the wall of Schlemm’s canal seem to modulate flow into the collector channels [29, 30]. This only seems to work when IOP is in the normal range [31]. Increasing episcleral venous pressure causes reflux of blood into Schlemm’s canal, indicating patency of the deep scleral plexus/collector channels. This reflux fails progressively with advancement of glaucoma [32, 33]. The anatomy and physiology of the outflow pathway have been comprehensively reviewed [2]. Consequences for (limitations of) MIG procedures have been discussed [34, 35].

It may be anticipated that both removal of SC inner wall and SC outer wall may reduce outflow resistance. Removal of SC outer wall (sinusotomy, deep sclerectomy) may reduce IOP. Success of stretching of Schlemm’s canal inner wall (canaloplasty) seems to depend on the patency of the distal outflow system. Grieshaber et al. [36, 37] demonstrated that blood reflux is associated with a higher success rate of the procedure. Bleaching of episcleral vessels after Trabectome is associated with success of the procedure [38, 39]. In cases without patent distal outflow system, there may be damage to the distal collector channels [25, 40].

SLT reduces IOP by about 20% [41, 42], but it seems more effective in newly diagnosed glaucoma [31], compliant with the hypothesis of a relatively intact distal outflow system early after diagnosis.

Limitations of our study comprise its retrospective nature and absence of control groups. Some of our patients have uveitis; it is known that angle surgery works in uveitis as this may explain part of the effect of this surgery. From a theoretical point of view, we limited our procedure for those cases with SIG with a limited duration of existence or with “active” steroid response. From the present study, it cannot definitely be concluded whether TO works (or not) in SIG with a longer duration of existence.