It is known that pseudoexfoliation glaucoma (PEXG)  is more aggressive than primary open-angle glaucoma (POAG) and scarcely responsive to medical treatment. Intraocular pressure (IOP) is usually higher and can show elevated spikes in eyes with PEXG compared to POAG, which may lead to a quicker progression of glaucomatous damage. Trabeculectomy using intra-operative antimetabolites remains the gold standard procedure in PEXG ^[1][2][2,3], even if the success rate seems to be lower in comparison with POAG ^[3][4][4,5]. Trabeculectomy is quite easy to perform and effective in reducing IOP; however, several late and early potentially serious complications can arise, such as hypotonus, atalamia, bleb infection, choroidal detachment, etc. Moreover, the scarring of conjunctival tissues, despite the use of antimetabolite drugs, often leads to a complete failure of this filtering operation over time.

Canaloplasty is a blebless, non-perforating technique, which became popular several years ago and involves the positioning and tensioning of a 10-0 prolene suture within Schlemm’s canal, which is previously dilated using a viscoelastic agent. This surgical technique can facilitate aqueous outflow through the natural pathways ^{[5][6][7][8][9][10][11][12]}[6,7,8,9,10,11,12,13]. The main indications for canaloplasty include POAG, juvenile glaucoma and pigmentary glaucoma. Even if PEXG is generally considered a good indication for canaloplasty, very few studies have specifically addressed this issue ^[13][14][15][14,15,16].

2. Canaloplasty Surgery in Pseudoexfoliation glaucoma Patients

Surgery is often required to reduce ocular hypertension and limit damage progression in PEXG patients, especially considering that functional damage can be rapid and severe in PEXG patients ^[16][17][18][18,19,20]. In eyes with advanced visual field loss, very low post-operative IOP values are needed to preserve the remnants of vision. Only filtering procedures, such as trabeculectomy or ExPress implant using antimetabolites, can offer these low IOP values and should be the preferred choice in these patients ^[19][21]. In selected patients who show mild to moderate functional damage, however, minimally invasive glaucoma surgery (MIGS) techniques, such as i-Stent implant ^[20][22], gonioscopy-assisted transluminal trabeculotomy ^[21][22][23,24] and XEN gel implant ^[23][24][25,26], can be taken into consideration. Non-perforating techniques, such as deep sclerectomy ^{[25][26][27][28]}[27,28,29,30] or canaloplasty, may be an interesting alternative, considering the higher hypotensive efficacy when compared to MIGS and the lower rate of complications compared to trabeculectomy. One of the main advantages of canaloplasty is that this type of surgery reduces IOP without requiring the formation of a filtering bleb ^[29][31]. For this reason, canaloplasty could be a viable option in selected patients having a high risk of conjunctival bleb failure with filtrating surgery, which is typically seen in eyes that have been treated with multiple local drop therapy for numerous years. This issue, however, needs further investigation considering the lack of studies in the current literature in this field. Another important advantage of this surgical option is the simplified follow-up and lower post-operative complication rates compared to the relatively high number of manipulations for blebs required after trabeculectomy (up to 78.2% of cases) ^[30][32]. The drawbacks of canaloplasty include the need for specific and expensive instrumentation and a steep learning curve. Another disadvantage, especially for beginners, is the proper cannulation of Schlemm’s canal, which can be difficult or not fully achieved in some cases. Canaloplasty, however, can be easily converted into a viscocanalostomy or a deep sclerectomy in these cases. In eyes that show mid-term failure after a successfully performed canaloplasty, a goniopuncture with YAG laser can be considered. In cases that do not show a sufficient reduction in IOP after canaloplasty and/or where medical therapy is not well tolerated or insufficient for lowering IOP, either a trabeculectomy or an implant of a drainage tube should be considered ^[31][33]. It is important to point out that in the researchers' cohort more than 60% of the PEXG eyes had an abrupt rise in IOP after years of satisfactory IOP stabilization. This long-term post-surgical complication, which is of utmost importance in these eyes at risk of functional progression, is poorly documented in the current literature ^[32][34]. According to the experience, this complication is more frequently observed two to four years after surgery. The pathogenetic mechanisms behind such a late complication are not well known and need to be addressed in future studies. One possible reason could be related to the continuous production and accumulation of pseudoexfoliative material in the angle structures which can occlude the existing compromised aqueous humor outflow pathways after a short period of time, which may be due to the physiopathological mechanisms of the disease and by the effects of numerous years of medical drugs. This hypothesis is supported by the observation that a similar late IOP rise can be found only in 13.7% of POAG eyes (personal unpublished data obtained from a cohort of 117 POAG patients with a similar follow-up period who underwent canaloplasty performed by the same surgeon). The prolene suture inside Schlemm’s canal could also be involved in the scarring process leading to the increase in outflow resistance. Future studies based on ultrasound biomicroscopy, preferably with 80 MHz transducers, or high-resolution anterior segment OCT ^[33][34][35,36], could help clarify, at least in part, the anatomical changes in Schlemm’s canal and in the trabecular meshwork in eyes showing long-term surgical failures. Histological studies conducted on human trabecular meshwork specimens could definitely provide a better comprehension behind the pathological post-operative induced structural changes in these eyes. The onset of important IOP spikes can give rise to acute signs and symptoms in these patients, especially if IOP reaches high values. Urgent trabeculectomy can usually be effective in normalizing IOP in these situations, especially considering that the conjunctiva tends to in good condition after a long period without local medical treatment. Unfortunately, in some cases, this rise in IOP can be slower and less pronounced and can go totally unnoticed, leading to a worsening of the damage already present, which can cause a potentially devastating visual impairment. Based on these clinically important considerations and the post-surgical risks involved, all patients with PEXG who have undergone canaloplasty should be carefully managed and thoroughly monitored for life The IOP cut-off values for the definition of success based on IOP values reported in the Methods section are not standardized and widely applicable in clinics; however, they have been used in several studies and are based on criteria reported in the World Glaucoma Association Guidelines published in 2009 ^[35][37]. The study adds to the very limited current literature in this field and could be of clinical importance to clinicians when managing post-surgical canaloplasty patients with PEXG. The results may help pave the way to future studies regarding physiopathological mechanisms behind acute IOP spikes in these patients, which could be due to decreased outflow related to the effects of the prolene suture in Schlemm’s canal. This could be of importance in those eyes with existing compromised angular tissue structures because of the long-term effects of PEX deposits, in addition to the cumulative side effects of numerous years of local medication. Comparative prospective studies based on traditional canaloplasty and surgery involving viscodilation of Schlemm’s canal without the positioning of a prolene suture (i.e., ab interno canaloplasty) could be useful in clarifying the potential effects on outflow mechanisms.