To the best of our knowledge, this is the first study evaluating surgical outcomes in trabeculotomy in patients with HM and OAG. We evaluated the postoperative success rate and outcomes in eyes with HM that were subjected to ab interno trabeculotomy. We detected a statistically significant cumulative probability of failure following trabeculotomy in HM eyes as compared to those in non-HM eyes, the success rate was 65% in the non-HM group at 36 months after surgery, whereas the success rate in the HM group was only 45%. And we identified that the presence of PM at baseline were important risk factors for surgical failure in HM patients with OAG. As MIGS has gained increasing attention among glaucoma specialists due to its safety profile and the ease of the technique, the present study provides important insights suggesting that trabeculotomy (and possibly outflow channel surgeries in general) have intrinsic limitations that should be considered in the surgical management of glaucoma in patients with HM.
Many population-based studies have shown that the prevalence of OAG increases with increasing myopia, and that the association with glaucomatous optic neuropathy is more pronounced in patients with moderate-to-high myopia [15, 16]. Numerous studies have likewise shown that refractive errors, especially medium-to-high myopia, are independent risk factors for OAG [15, 17, 18]. The reason myopic eyes (especially HM eyes) appear to be more susceptible to glaucomatous damage when compared with non-myopic eyes is unclear. However, we note that high myopia is an extreme form of myopia that causes excessive eyeball elongation. In turn, excessive elongation of the eyeball induces strong mechanical stress on all eye tissues, and this stress is associated with many severe comorbidities (such as retinal detachment, subretinal neovascularization, macular degeneration, and glaucoma) [19]. Recently, we showed that the increased fragility of the lamina cribrosa due to mechanical stress results in the development of glaucomatous visual field defects in patients with HM [20], which also indicates that excessive eyeball elongation may be a crucial risk factor in the development of glaucoma in HM patients. Chen et al. previously reported that HM patients have a larger Schlemm’s canal diameter and area as well as a decreased trabecular meshwork thickness [12] resulting from eyeball elongation. Schlemm's canal is a ring structure responsible for maintaining fluid homeostasis in the anterior chamber of the eye by draining the aqueous humor from the TM into the collecting channel. Obstruction of the aqueous humor flow in this conventional pathway leads to IOP elevation in glaucoma, which may in turn lead to poor outcomes in trabeculotomy. Thus, excessive eyeball elongation induces many morphological changes in HM eyes; these changes are responsible for the development of ocular disease and may affect treatment results.
According to the findings of previous studies, the level of surgical success for this procedure (typically defined as an IOP of ≤ 21 with a 20% decrease in IOP following standalone trabeculotomy surgery using MIGS) ranges from 45–60% [21–25]. Kaplowitz et al. alternatively defined surgical success as an IOP of ≤ 21 with a 20% postoperative decrease in IOP while avoiding reoperation; using this definition, the success rate for trabeculotomy using the Trabecutome procedure was 46 ± 3.4% two years postoperatively [21]. In addition, Gosling et al. defined surgical success as an IOP reduction of > 20% (IOP < 21 mm); these researchers showed that, given this definition, the success rate for trabeculotomy using TrabEX® was 54% at 25 months postoperatively [22]. The success rate of non-HM with OAG in the present study has good agreement with these previous studies. And we demonstrated that subjects with HM had significantly poor trabeculotomy surgery outcomes (45%) as compared with non-HM subjects (65%). To our knowledge, no previous studies have investigated long-term outcomes of trabeculotomy in HM patients. In the present study, our result become important evidence in a decision of applying trabeculotomy in HM patients. We speculate that poor surgical outcomes in HM patients may have several causes. First, HM is characterized by an above-normal axial length [19]; this elongation may be accompanied by an enlarged Schlemm’s canal diameter, as described previously [12]. Moreover, we note that intrascleral collector channels and the deep scleral plexus course through the sclera to the episcleral veins [26]; deformed and irregular eye shapes in HM may cause lesions and obstruction in intrascleral collector channels, leading to increased resistance distal to Schlemm’s canal and finally resulting in the expansion of Schlemm’s canal. Especially in HM eyes with PM, the deformation of eyeball is considered severe, and their sclera may be structural altered. Previous investigations have demonstrated marked thinning of the sclera, choroid, and retina in HM with stretching of the sclera, choroid, and retina caused by axial length elongation [27–29]; this may result in a disordered presentation of the intra-scleral collector channels, deep scleral plexus, and epi-scleral veins. Second, HM patients experience a series of collagen fiber changes [30] including a predominantly laminar collagen fiber bundle arrangement, a loss of fiber cross-links, and a reduction in collagen and glycosaminoglycan synthesis. Presumably, these changes increase the plasticity of collagen fibers and reduce their cross-linking stability. Changes in collagen fibers in HM (i.e., with regard to structure, biochemistry, and biomechanical properties around Schlemm’s canal) may lead to the obstruction of aqueous humor outflow into intra-scleral collector channels; these changes might also induce a functional failure in intra-scleral collector channels, the deep scleral plexus, and the epi-scleral veins. Third, recent studies have indicated that many metabolites and cytokines, such as interleukin-6 and matrix metalloproteinase-2 (known inflammatory factors in the aqueous humor), are statistically significantly altered in patients with HM [31]. This type of dysfunction in intraocular fluid could contribute to the formation of scars around the surgical area of the TM, which may inhibit aqueous humor outflow into collector channels and may contribute to the lower surgical success rate seen in HM. These findings require additional investigation. Relevant histological studies would help answer these questions more comprehensively.
And we also demonstrated the presence of PM is a risk factor for failure of trabeculotomy in HM patients in the present study. PM differs distinctly from HM with regard to a range of parameters. For example, high myopia is characterized by a high degree of myopic refractive error, whereas PM is defined by the presence of typical complications in the posterior fundus. Refractive error or axial length alone often does not adequately reflect PM [32]. Indeed, the AXL was not statistical risk factor for trabeculotomy in HM patients in the present study. In the META-PM classification, PM is defined according to a categorization that is equal to or greater than myopic maculopathy (Category 2) [2]. In the current study, we demonstrated 11 eyes showed PM among the 20 eyes, and nine in the 11 eyes exhibiting surgical failure in HM patients with OAG. This high ratio of PM in the surgical failure group is remarkable. In higher grade of PM, the structure of retina dramatically is altered, and it is possible that the abnormality of tissue structure of the eyes may cover a wide area such as sclera. In HM eyes, some scleral abnormalities were previously reported such as thinning of sclera, posterior staphyloma and myopic scleral pit [33, 34], which may influence aqueous humor outflow, especially in the PM eyes. Taken together, it is reasonable our results that the outcome of trabeculotomy in PM patients was not favorable. We should pay attention the presence of PM before trabeculotomy surgery in HM patients. The presence of PM may be the most important factors predicting trabeculotomy outcomes in HM patients.
A limitation of the present study is that the included data were obtained from a relatively small number of eyes. However, this is the first to identified 36 months standalone ab interno trabeculotomy outcome in patients with HM, and relatively few OAG patients with extremely long axial length were included in our study (mean axial length, 30.1 mm), which may support future study. We also note that a longer follow-up study is needed for the long-term evaluation of glaucoma surgery outcomes and that, in general, large-scale and long-term studies are needed to confirm our findings more definitively. However, we preliminarily conclude that the long-term efficacy and safety of ab interno trabeculotomy in HM eyes with OAG may be inferior to that in non-HM eyes with OAG.