Role of Scleral, Episcleral and Conjunctival Lymphatics in Suprachoroidal Drainage

1. Introduction

At present, in the management of open-angle glaucoma (OAG), increased intraocular pressure (IOP) is the only factor affected by IOP-lowering medications and laser or surgical techniques. Aqueous humor (AH) outflows from the anterior chamber (AC) via two main pathways: trabecular (conventional) and non-trabecular (nonconventional) [1].

Despite the vast potential to lower IOP in glaucoma patients, the non-trabecular outflow pathway is the least investigated area to date. Cyclodialysis (detachment of the ciliary body from the scleral spur to create a cyclodialysis cleft), first performed by Heine L. in 1905, was the most common surgical procedure for treating glaucoma before trabeculectomy [2]. The surgery decreased IOP significantly, but the long-term results were unpredictable, and the cyclodialysis cleft had a tendency to close. Various implants and scaffolds to keep the cleft open and operational have been proposed and implemented with limited success [3,4,5,6,7]. Detaching the ciliary body from the scleral spur is a traumatic procedure that could lead to inflammation and fibrosis at the surgical site and may be a logical explanation for cleft closure. This calls for the development of surgical techniques that enable rerouting of AH flow from the AC to the SCS exclusively without cyclodialysis while preventing AH leakage to the subconjunctival space.

A two-stage approach was developed to achieve these objectives [8]. First, an intrascleral chamber (ISC) was created by excising a block of deep scleral tissue, along with the external wall of Schlemm’s canal (SC). To avoid filtration in the early postoperative period, no window was made in Descemet’s membrane. A biodegradable collagen implant was placed with one end in the ISC and the other in the SCS to function as a spacer and conduit. Postoperatively, Nd:YAG laser trabeculotomy (YAG-LT) was performed to allow AH to flow from the AC to the intrascleral pool and from there to the SCS. This technique proved to be highly efficient in lowering IOP without forming a filtration bleb (FB), which was confirmed by optical coherence tomography (OCT). In early cases, interesting observations were made during postoperative follow-ups. On slit lamp examination, in nearly 50% of cases, various forms and shapes of transparent conjunctival lymphatic vessels (CLVs) became visible in the superior bulbar conjunctiva. The efficacy and safety of the proposed technique were evaluated in a consecutive case series consisting of 38 patients, in which the same results were achieved [9]. This led to a hypothesis that cyclodialysis-independent enhancement of the non-trabecular outflow pathway resulted in the activation of not only the uveoscleral, uveovortex and uveolymphatic routes but also a novel pathway: the SCS–scleral–episcleral–CLV route. Restoration of a functional lymphatic system resulted in a significant decrease in IOP. This interventional consecutive case series reports long-term clinical outcomes of the proposed technique to support this hypothesis.

2. Materials and Methods

This is a clinical, interventional, non-comparative consecutive case series. In this retrospective cohort study, the medical records of ninety-eight patients (104 eyes) who underwent surgery from March 1, 2020, to March 31, 2025, were selected and analyzed. Sixty-three patients (70 eyes) fulfilled the inclusion criteria and were included in this study. A standalone procedure was performed in 22 eyes (31.4%) and in combination with cataract surgery in 48 eyes (68.6%). One surgeon (VK) conducted all the operations.

The patients included were those who provided informed consent and had OAG in phakic eyes with or without visually significant cataract or with pseudophakia, medically uncontrolled IOP, non-compliance with prescribed hypotensive medication, and decompensated IOP after previous glaucoma surgeries. Inclusion required a minimum follow-up of 6 months, with data collected longitudinally for up to 36 months after baseline.

The exclusion criteria were narrow-angle or closed-angle glaucoma, acute attack of glaucoma, neovascular glaucoma, congenital glaucoma, phacolytic or phacomorphic glaucoma, rubeosis or angle abnormalities, any significant ocular comorbid disease, inability to discontinue use of blood thinners, history of uveitis or infection within 90 days before screening in either eye or ocular pathology that may interfere with accurate IOP measurements.

Before surgery, a comprehensive ophthalmological examination was conducted, including a visual acuity (VA) assessment using Snellen’s chart (values converted to logMAR for analysis purposes), tonometry, perimetry, ophthalmoscopy and optical coherence tomography (OCT) using a SOCT Copernicus Revo 80 (OPTOPOL Technology Sp.z.o.o., Zawiercie, Poland). On OCT, if the native lens condition permitted, glaucoma analysis (RNFL, ONH morphology, DDLS, Ganglion analysis as RNFL + GCL + IP and GCL + IPL, OU, and hemisphere asymmetry) was also carried out. Every patient underwent OCT of the superior bulbar conjunctiva to identify CLVs.

No preoperative change was made in the patient’s ocular hypotensive medication regimen. Antibacterial (sol. Levofloxacin 0.5%, 1–2 drops 3 times a day) and anti-inflammatory (sol. bromfenac 0.09%, once a day) medications were prescribed for a period of three days before surgery. Glaucoma medications were counted as two separate medications.

The study protocol was approved by the research Ethics Committee of the Medical Institute of the Patrice Lumumba People’s Friendship University of Russia, Moscow, and complied with the principles of the Declaration of Helsinki. Written informed consent was obtained from all patients included in the study.

2.1. Surgical Technique

The surgical technique has been described in detail elsewhere [8,9]. Retrobulbar anesthesia was preferred. A traction suture was applied at the limbus at either the 12-00 or 18-00 o’clock position. In standalone cases, before attempting glaucoma surgery, a 1.5 to 2.0 mm wide clear corneal incision was made, and the AC was partially filled with a cohesive viscoelastic device (1-1.4% hyaluronic acid solution). Peripheral iridotomy was performed using capsulorhexis needle with the Oertli CataRhex 3 apparatus (supplementary material: video S1). The viscoelastic device was then irrigated out, and the incision was hydrated. After fornix-based conjunctival peritomy, a 4 × 4 mm 1/3 thick limbal-based superficial scleral flap was fashioned. Parallel to the limbus and 2, 3 and 4 mm away from it, three transversal incisions up to the uveal tissue were made in the deep scleral layers to divide them into three parts. In the distal part, deep scleral tissue was excised along with the external wall of the SC, leaving a small amount of sclera over the ciliary body. No window was created in Descemet’s membrane. Part of the juxtacanalicular connective tissue was stripped from the inner wall of the SC and removed. Under the middle and proximal parts of the sclera, the uvea was detached from the overlying sclera using a thin, blunt spatula. Using forceps, a strip of biodegradable collagen implant (MakMedi glaucoma drainage, Russia) was inserted into the cleft with its anterior end in the ISC to act as a spacer and conduit. The proximal scleral part was completely excised, exposing a wider uveal surface area for contact with AH (Figure 1). At the end, the superficial scleral flap was replaced and sutured watertight with five interrupted 10–0 nylon sutures. The conjunctiva was then sutured back to the limbus (supplementary material: video S2).

A two-site approach was employed for combined surgery. First, cataract surgery was performed. After intraocular lens (IOL) implantation, the viscoelastic device was irrigated out, and the pupil was constricted by irrigating the AC with 0.01% carbachol solution (sol. Miochol 0.01%, Appasamy ocular devices, India). The AC was then partially refilled with the viscoelastic device, and a peripheral iridotomy was made using capsulorhexis needle with the CataRhex 3 apparatus (Oertli instruments, Switzerland). The viscoelastic device was removed from the AC by irrigation and aspiration, and an interrupted suture was placed on the main incision. Glaucoma surgery was then attempted at 12:00. In patients who had undergone previous glaucoma procedures, the surgery was performed in areas close to the previous surgical site so as not to disturb it.

Postoperatively, in some cases, it was difficult to identify the exact location of the surgical site on gonioscopy. To solve this problem, the technique was modified slightly. Two small pieces (0.5cm each) of 4-0 or 5-0 polypropylene suture were inserted into both open ends of the SC (supplementary material: video S3). This helped to identify the surgical site during gonioscopy (Figure 2a, b). The ‘scleral bridge’ was further thinned out, leaving about 25% of sclera over the uveal tissue. This increased the contact surface area of uvea with AH.

The primary outcome was the proportion of eyes with a final IOP < 18 mm Hg and a > 20% reduction in IOP with the same or fewer medications compared to baseline. Secondary outcomes were the mean changes in IOP at different postoperative follow-ups, and changes in the number of IOP-lowering medications compared with baseline.

Regarding safety outcomes, eyes with intraoperative and postoperative complications, those requiring further glaucoma surgery, and eyes with a loss of 2 or more lines of vision were reported.

A standard postoperative protocol was followed, including the instillation of topical dexamethasone 0.1% (administered 3 times daily for 1 week, reduced to twice daily for the 2^nd week and further reduced to once daily for the 3^rd week) and antibiotic eye drops (sol. Moxifloxacin 0.5% or sol. Levofloxacin 0.5%, 3 times daily for one week). Patients were evaluated the next day and based upon their IOP level, were instructed to either continue or discontinue the instillation of hypotensive medications. Conjunctival sutures were removed on days 7 –10 after surgery.

Postoperative assessment included VA assessment, tonometry, biomicroscopy, ophthalmoscopy, gonioscopy and OCT evaluation of the surgical site and areas adjacent to it. Wherever possible, findings were documented via photography and videography. Follow-up visits were scheduled for day one, weekly for the 1^st month, monthly for up to 3 months, every 3-4 months for the 1^st year and every 6 months thereafter. Patients with suboptimal IOP control required more frequent visits. In cases of high IOP, YAG-LT was performed using a slit lamp-mounted Nd:YAG laser (Optotek Medical optoYAG, Slovenia) and a single mirror laser gonio lens (Ocular Latina Gonio Laser Lens, Ocular Instruments, Bellevue, WA, USA). The procedure was performed no earlier than 7-10 days after surgery. This period was needed for the conjunctiva to heal completely, with the underlying scleral tissue preventing any leakage of AH from the ISC to the subconjunctival space. Usually, 3 or 5 millijoules of energy were used, and one or more openings were created in the trabecular meshwork. In a successful trabeculotomy, pulsatile movement of AH passing through was detected. After the procedure, patients were advised to use non-steroidal anti-inflammatory eye drops (Bromfenac ophthalmic solution 0.09%) once daily for days 7 to 10. If LT was performed within month 1 after surgery, for analysis purposes, the first postoperative day was the day following the LT. Patients with IOP >18mm Hg even after YAG-LT were started on antiglaucoma medications. Those with uncontrolled IOP, despite YAG-LT and maximal therapy, were considered for additional glaucoma surgery.

During OCT, patients were asked to look down, and the upper lid was retracted to expose the surgical site. Five horizontal and five vertical Raster scans 1 mm apart were obtained. The scans were assessed qualitatively. The scan was considered good-quality if the scleral flap, collagen implant, scleral lake, internal fluid-filled cavities and AH drainage routes were identifiable. FBs were defined as the internal fluid-filled cavities with significantly low-reflective fluid-filled spaces adjacent to the scleral flap. The hyporeflective area was delineated by the hyperreflective conjunctiva and Tenon’s capsule in the bleb. Microcyst was defined as a small round hyporeflective space more than 10 μm in diameter in the bleb wall (in the epithelial layer) [10]. Lymphatic vessels were defined as hyporeflective spaces with characteristic bicuspid valves in their lumen.

Success was defined as a final IOP < 18 mm Hg with an IOP reduction > 20% in patients on the same number of hypotensive medications or less and without severe loss of vision (loss of more than 2 lines in Snellen’s VA chart). Failure was defined as an IOP level measured above the upper limit or below the lower limit on two consecutive visits and in the case of a need for further glaucoma intervention other than YAG-LT or iridotomy and the loss of 2 or more Snellen’s VA lines. The date of failure was the midpoint between the last day of success and the first day of failure. Hypotony was defined as having IOP of less than 5 mmHg with persistent macula folds, edema or choroidal effusion observed on dilated fundus examination and OCT.

The ophthalmic collagen implants (MakMedi, Moscow, Russia) were made from a natural biopolymer—the connective tissue collagen of farm animals (made from the sclera of swine eyes). The implant used in this study is a certified medical item registered with the competent authorities of the country in which the study was conducted. They are ophthalmic collagen implants meant for use in glaucoma surgery and are permitted for use in human beings (Registration № RU № FC 01032006/3759-06 dated 23.10.2006). They are commercially available in different shapes and sizes; for this study, rectangular implants measuring 0.1 × 2.0 × 5.0–6.0 mm were selected. The implants have a unique layered-cell structure with large interlayer spaces. When immersed in fluid, they swell and increase in thickness while the frontal dimensions remain practically unchanged. According to the manufacturer, when implanted in eye tissue, the implant is slowly resorbed by tissue fluids over time.

2.2. Statistics

Continuous variables were described as means with standard deviations (SDs). Categorical variables were described with the frequency as a percentage. A paired t-test procedure was employed to determine the significance of the mean change in IOP and in the number of glaucoma medications from the baseline to different timepoints. The success of treatment was expressed as a Kaplan–Meier curve. p-values below 0.05 were considered statistically significant. SPSS Statistics (IBM) 22.0.0.0 software and Microsoft Office 365 Excel were used for statistical processing.

3. Results

Demographic and baseline clinical characteristics are summarized in Table 1.

YAG-LT was performed in 51 eyes (72.9%). In most cases (43 eyes, 84.4%), the procedure was needed within one month after surgery. Between months 1 and 3, the procedure was performed in another four eyes (7.8%), and in another four eyes (7.8%) after 6 months. One procedure was sufficient to lower the IOP in 36 eyes (70.6%). In 15 eyes (29.4%), the procedure was repeated more than one time; of these eyes, the procedure was performed two times in 11 eyes (21.6%), three times in 2 eyes (3.9%) and four times in another 2 eyes (3.9%). Visually detectable fluid movement, including tiny pigment particles, from the AC to the LT opening immediately after LT was observed in 35 eyes (68.6%). Some blood oozed from the SC in seven cases, resulting in hyphema in one case. The blood from the AC dissolved spontaneously without any special treatment. YAG-LT resulted in a decrease in the IOP to the target level in 49 eyes (96.1%). The need for YAG-LT was greater in eyes that had undergone previous filtering surgery. Out of 18 such eyes, the procedure was required in 15 (83.3%) (1 time in 9 eyes, 2 times in 5 eyes and 3 times in 1 eye).

3.1. Efficacy

IOP reductions at different follow-up intervals and changes in IOP after surgery (mean IOP decrease and percentage reduction in IOP in comparison to baseline at different postoperative intervals) are presented in Table 2 and Table 3 and in Figure 3.

The primary outcome was achieved in 90.1, 88.3, 90.4, 93.5, 96.2 and 100% of cases at months 6, 12, 18, 24, 30 and 36, respectively.

Changes in the use of hypotensive medications after surgery are reported in Table 4 and Table 5.

In total, 32 eyes (45.7%) did not receive any IOP-lowering eye drops after surgery. In 38 eyes (54.3%), the surgery was effective for a certain period of time, after which additional hypotensive medications were required to lower the IOP to the target level.

Complete success was achieved in 32 eyes (45.7%), and partial success was achieved in 21 eyes (30.0%). Outcomes were unsatisfactory for seventeen eyes (24.3%), out of which seven (41.2%, 7/17) were declared failure cases within one month after surgery. In contrast, in three, one, one, three, one and one eye, the hypotensive effect of the surgery lasted for 3, 6, 9, 12, 18 and 30 months, respectively, after which additional medication was prescribed to lower the IOP. In the eyes that had previously undergone glaucoma surgery (18 eyes), complete success was achieved in 44.4% and partial in 55.6%.

The success of the treatment, expressed using a Kaplan–Meier curve, is illustrated in Figure 4.

Kaplan–Meier survival curves after surgery in the standalone surgery and combined surgery groups are presented in Figure 5.

3.2. Safety

Most of the difficulties encountered during surgery were related to cataract surgery for intumescent cataracts and in eyes with pseudo-exfoliation syndrome, where the pupils were rigid and resistant to dilation, necessitating the use of different pupil-dilating devices and manipulations. In all cases with previously unsuccessful filtration surgeries, the surgeon faced difficulties in dissecting the conjunctival and scleral flaps. There was no difficulty with inserting the CI into the suprachoroidal tunnel in any case.

Postoperatively, one patient had a spontaneous retinal hemorrhage unrelated to the surgery, which resolved after one month with vision restoration. In another case, blood oozed from the SC after YAG-LT, with the patient developing hyphema; this resolved spontaneously within week one ((supplementary material: video S4). This patient had a history of diabetes. There were no cases of hypotony, shallow AC or choroidal effusion during the follow-up period.

The median VA (logMar) before surgery was 0.6 [0.2;1.9]. Changes in VA after surgery over time are presented in Table 6.

3.3. Biomicroscopic Visualization of CLVs After Surgery

On slit lamp examination, some conjunctival swelling at the surgical site due to surgical trauma was noticed in all cases in the first few days after surgery. Except for one case in which a bleb formed, lasting for a period of one week, no blebs were identified. Transparent CLVs appeared in different parts of the superior bulbar conjunctiva at different postoperative intervals in 37 eyes (52.9%, 37/70) (Table 7 and Table 8). The preferred site for CLVs was the superior nasal quadrant, where they were visualized 46 times, followed by the superior temporal quadrant at 17 times.

The lymphatic nature of these transparent vessels was confirmed in all cases by OCT. They had bicuspid valve-like structures in their lumen (Figure 6a-d, Figure 7 a-b).

As these vessels were transparent, some maneuvers were required to visualize them. Moving the upper lid margin over the conjunctiva sometimes helped in detecting the hidden CLVs, as shown in Figure 8 a-c, Figure 9 a-c and Figure 10 a-d (supplementary material: video S5).

Out of 51 eyes in which YAG-LT was performed, CLVs appeared immediately after the procedure in 6 (Figure 11 1a-c, 2a-c, 3a-c) (supplementary material: figure S11, video S6). CLVs appeared later in other eyes.

In most cases (31/37 eyes; 83.8%), these vessels appeared within 1 month after surgery or YAG-LT.

In terms of duration, in 73% of cases (27/37 eyes), these vessels lasted for a maximum period of <1 month.

It was observed that, as a rule, in eyes in which CLVs became visible after surgery without LT and disappeared over time, they reappeared in the same place following YAG-LT. This is clearly shown in Figure 12.

It was common for CLVs to arise directly from the sclera in areas far from the surgical site, with no connection to the surgical site (Figure 6 b, 7a, 11 2a, 3a; Figure 12 1c, 2c, 3c, 13a).

No pattern in their appearance was identified. Sometimes they appeared running parallel to the limbus (Figure 6b and Figure 8a-c, 12 1c–3c, 13a) and other times perpendicular to it; in some cases, a plexus was observed (Figure 8 a-c, 10 c, d), and in other cases, they remained as isolated 1 or 2 vessels (supplementary material: video S7).

In some cases, especially eyes in which YAG-LT was performed when the IOP was high, it was possible to differentiate between layers of CLVs (superficial and deep conjunctival lymphatic vessels) immediately or after some period after the procedure (Figure 13 b) (supplementary material: video S8).

The numbers and sizes of the biomicroscopic visible CLVs were related to the IOP level. A relationship between biomicroscopic visualization of CLV and an unsatisfactory hypotensive effect after surgery was established. Out of 17 cases considered to have unsatisfactory results, there were 10 in which CLVs were visualized using a slit lamp microscope, indicating a rate of 58.8%. Another relationship exists between the biomicroscopic visualization of CLVs and the need for additional hypotensive medications to control IOP. Among the eyes in need of additional postoperative medications (38 eyes), there were 24 (63.2%, 24/38) with CLVs; in other words, out of 37 eyes with biomicroscopic visible CLVs, 24 required additional medication, making it 64.9%.

3.4. OCT Identification of CLVs After Surgery

Analysis of OCT evaluation of the superior bulbar conjunctiva, which was part of the standard protocol for pre- and postoperative evaluations of the patients, showed that in a real-world scenario, it was not possible to perform OCT in every case at each postoperative follow-up interval. Patients were scheduled for OCT examinations at week 1 and months 1, 3, 6, 9, 12, 18, 24, 30 and 36. Out of 595 OCT investigations that should have been performed according to protocol, only 209 were possible, resulting in 35.1% coverage (Table 9). There were 14 patients in whom postoperative OCT evaluation was not performed at all due to a variety of unavoidable obstacles. In the other 56 eyes, OCT was performed once only in 15 (26.8%) cases, twice in 7 cases (12.5%), three times in 14 cases (25%) and more than three times in 20 cases (35.7%). Timewise, OCT was performed at week 1 in 24 cases (42.9%, 24/56) and at month 3 in 60.7% (34/56) of cases. For months 12, 24 and 30, OCT was performed in 37.5% (21/56), 45.2% (14/31) and 38.5% (10/26) of cases, respectively. For analysis purposes, 56 eyes that underwent postoperative OCT were considered.

No bleb formation occurred in any of the cases (Figure 14). In one case, a bleb cavity was diagnosed by OCT and lasted for a short period of 1 week.

Before surgery, no CLVs were identified on OCT in the superior bulbar conjunctiva in any of the cases. After surgery, CLVs were identified on OCT in 53 cases (94.6%, 53/56). There was no report of identified CLVs in the records of the other three cases.

Results of the postoperative OCT evaluation and the distribution of identified CLVs in the superior bulbar conjunctiva at different follow-up intervals are presented in Table 9.

Location-wise, in 22.5% of cases, CLVs were identified in all investigated areas, followed by simultaneous identification at the superior temporal and medial quadrants in 17.2% of eyes. In 16.8% of cases, the CLVs were only identified in the superior medial quadrant and in 10.5%, only in the superior temporal quadrant. Identification of CLVs at the surgical site only was observed in 9.6% of cases.

Out of 32 cases having achieved complete success, CLVs on OCT were identified in 25 cases (78.1%), whereas in 7 cases (21.9%), there were no CLVs identified (p<0.0001). In cases with partial success (38 eyes), CLVs were identified in 12 cases (31.6%), whereas in 10 cases (26.3%) they were absent. In the other 10 cases (26.3%), CLVs were identified in the early postoperative period but disappeared afterwards, indicating a nonfunctioning conjunctival lymphatic system. In another six cases (15.8%) the CLVs appeared after a certain follow-up period, indicating that some time was needed before the lymphatic system became operational.

3.5. Analysis of Cases with Unsatisfactory Results

Seventeen cases (24.3%) had unsatisfactory outcomes. Seven (41.2%) were declared failures within 1 month after surgery, and three cases each at 3 and 12 months were also considered failures. At each of the 6-, 9-, 18- and 30-month follow-ups, one case had an unsatisfactory result. Among these cases, >40% (7/17) of patients were suffering from advanced glaucoma, and nearly 65% (11/17) were taking >3 classes of hypotensive medications. Four patients (23.5%) had previously been operated on for glaucoma. In nearly 60% of cases (10/17), CLVs were observed biomicroscopically.

3.6. Subgroup Analysis: Standalone Group Versus Combined Surgery Group

Gender, age, laterality, latest follow-up, mean preoperative IOP, medication burden and VA were the same in both groups (Table 1). In the standalone group, YAG-LT was required in most eyes—20 (90.9%)—whereas in the combined surgery group, this procedure was needed in 31 eyes only (64.6%) (p=0.034). The number of eyes requiring YAG-LT more than once was the same in both groups. IOP reductions at different follow-up intervals were also the same in both groups, except at 18 and 24 months. The mean IOP (SD) reductions at months 3, 6, 12, 18, 24 and 30 were -17.3 (10.3) and -13.9 (8.3) (p=0.187), -16.8 (10.8) and -13.2 (8.0) (p=0.175), -14.9 (12.4) and -12.0 (8.1) (p=0.366), -18.2 (10.7) and -11.2 (6.1) (p=0.048), -20.6 (10.7) and -12.8 (7.9) (p=0.052) for the standalone surgery group and combined surgery group, respectively. In comparison to the baseline IOP values, the IOP reduction was statistically significant (p<0.0001) in both groups at all follow-up intervals. Percentagewise, the IOP reduction was also the same in both groups except at months 18 and 24, where the IOP reduction was significantly greater in the standalone surgery group. The difference in the number of cases with complete success was statistically insignificant in both groups except for the month 36. All patients in the standalone surgery group (7 cases) who had 36 months of follow-up needed additional medications, whereas in the combined surgery group, the percentage of such cases was 60% (9/15). Throughout the follow-up period, the need for additional hypotensive medication was the same in both surgery groups, which was also true for patients who underwent a second glaucoma surgery.

There were few complications in both groups, and they were related to the YAG-LT procedure only.

In the standalone surgery group, the median VA changed from the baseline 0.7[0.2;1.8] to 0.6[0.1;1.2], 0.5[0.2;1.7], 0.4[0.2;1.7], 0.5[0.2;1.7], 0.4[0;0.6] and 0[0;0.8] at months 6, 18, 24, 30 and 36, respectively. In the combined surgery group, the median VA changed from the baseline 0.5[0.2;1.7] to 0.1[0;0.4], 0.1[0;0.3], 0.1[0;0.2], 0[0;0.2], 0[0;0.1] and 0[0;0.1] at months 6, 18, 24, 30 and 36, respectively (Table 6b). In the combined surgery group, VA deteriorated over time in three cases due to the development of secondary cataract. YAG laser capsulotomy restored vision.

Out of 17 patients with unsatisfactory results, 6 (27.3%, 6/22) were in the standalone surgery subgroup, and 11 (22.9%, 11/48) were in the combined surgery subgroup (Table 7). The difference between subgroups was statistically insignificant (P= 0.534; Chi-square test).

3.7. Case Reports

Case 1. This clinical case demonstrates the role of lymphatics in suprachoroidal drainage to decrease IOP. A 54-year-old female patient suffering from glaucoma in her left eye since 2022, with an IOP of 27 mm Hg, and on three classes of hypotensive medication, was operated upon on March 23, 2023, applying the technique described above. The patient had an intolerance to most IOP-lowering medications. Postoperatively, the patient’s IOP remained below 13 mm Hg for a period of 10 months without medication and without YAG-LT, after which the patient started having episodes of increased IOP. To lower the IOP, YAG-LT was performed, after which IOP normalized and remained in the range of 8 to 13 mm Hg. Immediately after LT, a few CLVs appeared in the superior conjunctiva near the surgical field, which were identifiable biomicroscopically. These vessels disappeared after 2 days. Further follow-up of the patient revealed several episodes of increases in IOP, which were associated with oppositional occlusion of the trabeclotomy foramen by the iris root. Instillation of 1% pilocarpine normalized the IOP to single digits, but the patient showed pronounced intolerance to pilocarpine. Replacement of the native lens with an IOL was proposed in order to provide an uninterrupted outflow of AH through the trabeculotomy. This was discussed with the patient, and written consent was obtained from her. Before phacoemulsification, the possible AH outflow pathway was studied. The AH in the AC was replaced with an aqueous tracer dye (0.08% solution of trypan blue). The procedure was performed with an operating microscope capable of video recording. Simultaneous video recording of the superior bulbar conjunctiva at the surgical and nearby sites was performed. The obtained results are presented in a series of snaps made from a video clip of the procedure (Figure 15 a-l). Using “Movavi Video Editor 2024” software, the video clip was edited using the timer application. The video clip is provided as supplementary material Video S9.

Case 2. An in vivo investigation of CLV distribution at the time of glaucoma surgery revealed the existence of a close network consisting of CLVs and episcleral and scleral lymphatic vessels interlacing with each other. Earlier, Gusev AM discovered, in the limbal area, a connection between conjunctival lymphatic capillaries and episcleral lymphatic capillaries [11]. To study the lymphatic system of the conjunctiva, the author used an interstitial injection of a modified Gerota mass, which is a suspension to be injected into the lymphatic and blood vessels of a cadaver while preparing anatomical specimens. In our investigation, trypan blue dye was injected into the conjunctival tissue with the help of a 34G injection needle, with the hope that some dye would enter some of the lymphatic vessels. The needle directly punctured a lymph vessel, and the slow injection of dye manifested in the development of a whole lymph tree demonstrating the connections between different layers of the CLVs of the conjunctival lymphatic system. The flow pattern of the dye and the relationship of CLVs with episcleral and scleral lymphatics are shown in Figure 16 a-j. A video clip of the investigation is provided as supplementary material Video S10.

4. Discussion

In nature, the AH flows in a closed system with a bulk flow mechanism. It flows out of the eye primarily through the trabecular (conventional) outflow pathway, which includes the trabecular meshwork, SC, collector channels, aqueous veins and episcleral veins. This outflow pathway is IOP-dependent [1].

Bill A. and colleagues were the first to discover another outflow pathway, which they termed the ‘unconventional route’. Authors perfused radiolabeled molecules of various sizes through the ACs of various animal eyes (monkeys, rabbits and cats) to study different routes by which the fluid left the eye [12,13,14,15,16,17,18]. They found that only about 80% of the tracer left the eye through the trabecular outflow pathway. The remaining tracer accumulated in the ciliary body, choroid, and sclera and based upon his findings, proposed that there exists another route for AH to flow from the AC through the uvea and into the sclera by way of the choroid and suprachoroid [14,15,17,18].

Bill A. and Phillips C.I. [19] confirmed the occurrence of uveoscleral drainage of AH, which had been demonstrated previously in animal eyes, particularly in monkeys, in human eyes [16].

The non-trabecular outflow pathway consists of the ciliary muscle, supraciliary and SCS. The supraciliary space is located anteriorly between the outer surface of the ciliary body and the internal surface of the sclera. The SCS is located posteriorly between the choroid and the internal surface of the sclera. AH passes from the AC through the most posterior aspects of the uveal meshwork, enters the open spaces between longitudinal aspects of the ciliary muscle and then enters the SCS [20,21,22].

Morphologically, the SCS is not simply a space. Karlova and others [23] perfused 36 human cadaver eyeballs using a 5% suspension of India ink in a balanced saline solution and discovered a system of suprachoroidal plates ensuring a unidirectional movement of fluid from the posterior edge of the ciliary muscle to the equatorial region and further to the posterior pole of the eye. The reverse flow of fluid (from the equator to the limbus) caused the suprachoroidal plates to rise, making it impossible for the fluid to move anteriorly. As per the authors’ description, the trabecular apparatus is a unique structure with a complex spatial organization that facilitates fluid flow 1) through the layers of the trabeculae to the SC and 2) along the layers of uveal trabeculae into the longitudinal spaces between the bundles of the ciliary muscle (uveal tract), forming the uveal or uveoscleral outflow. From the ciliary muscle, fluid moves to the SCS, where the valvular structure of the suprachoroid provides unidirectional movement from the place of its exit to the paravascular spaces of the sclera in the posterior segment of the eye.

Krohn J, Bertelsen T. [24] carried out a study to visualize the SCS and to study the morphology of possible uveoscleral drainage routes in the human eye. The authors injected Indian-ink-stained gelatine directly into the SCSs of seven human donor eyes. The quadrants in which gelatine appeared in the episcleral venous network were cut in their entirety in consecutive sections and examined by light microscopy. They observed gelatine in the connective tissue surrounding the scleral vessels and nerves and in fine, endothelium-lined channels at the inner aspect of the anterior sclera, which originated at the inner surface of the sclera, close behind the scleral spur, and communicated with the intrascleral venous plexus. The authors concluded that fluid drains from the SCS through the perivascular and perineural spaces of the scleral blood vessels and nerves. This study also indicated that there are preformed channels at the inner aspect of the anterior sclera capable of draining fluid directly into scleral veins.

The same authors confirmed their findings using a corrosion casting technique. Batson’s mixture No. 17 (methyl methacrylate) was injected through a sclerotomy into the SCSs of human cadaver eyes. Following polymerization of the injected mixture, the surrounding tissue was dissolved with 10% natrium hydroxide and macroscopic and scanning electron microscopic examination were carried out. The authors observed transscleral drainage of resin and found different types of branches derived from the outer (scleral) surface of the casts. Some of these branches corresponded to the perivascular spaces of both ciliary vessels and vortex veins. In addition, the authors found branches that likely represented channels derived directly from the SCS, communicating with the intrascleral venous plexus [25].

Bill A. ligated the large cervical lymph vessels and all other connections between the cervical and thoracic lymph vessels near the thoracic aperture of a rabbit [26]. After ligating the lymph vessels, the cervical lymph vessels on the head side of the ligations were opened to allow free outflow of lymph. Then, 2μl of the labeled albumin solution was injected into the SCS. Based upon the results of the experiments, the author concluded that the albumin left the SCS by bulk flow and that >85% passed out through the sclera and was collected by lymph vessels. The author also noticed that disconnecting the cervical lymph paths from the large veins did not wholly prevent the passage of labeled albumin into the general circulation, and about 15% still reached the blood.

The non-trabecular outflow is controlled by the resistance imparted by the ciliary muscle bundles and the connective tissue of the ciliary body. The flow through this pathway is pressure-independent. The pressure in the suprauveal and SCS is a little lower than the IOP, creating a pressure gradient. An increase in pressure in the AC has little effect on the pressure gradient [27]. This pathway can be turned into a pressure-dependent pathway bypassing the ciliary muscle, as in cyclodialysis. When the uveo-scleral route is turned into a pressure-dependent pathway, the decrease in IOP is very significant, and the postoperative IOP can reach the low teens or single digits [28].

AH leaves the SCS by uveo-scleral, uveovortex and uveo-lymphatic routes [13,29,30]. To study the possible routes by which labeled albumin introduced into the SCS leaves the eye, Bill A. injected albumin labeled with Evans blue and ¹³¹I into the SCSs of rabbits and investigated tissues at different intervals after the injection, observing that after 60 minutes, > 60% of the labeled material had left the eye and a considerable part of the albumin entered the conjunctiva and left by way of the conjunctival lymphatics, draining into regional lymph nodes which, in turn, drained into the superficial cervical lymph vessels [13]. The author concluded that labeled albumin injected into the SCS penetrated the sclera through the perivascular spaces and most likely also through other pathways, finally moving into the conjunctiva where it was collected by conjunctival lymph vessels.

Reports confirmed that uveoscleral flow depends upon scleral permeability [1].

Barany E. [29], Pederson JE et al. [31], and Sherman SH et al. [32] proposed that a fraction of fluid in the SCS is absorbed osmotically by the choroid and passes into the vortex veins (the uveovortex pathway). The outflow is driven by a large colloidal osmotic gradient.

Yucel Y. et al. [30,33] described and proved the presence of a uveolymphatic pathway for AH drainage using specific lymphatic markers such as podoplanin, a transmembrane mucin-type glycoprotein, and lymphatic vessel endothelial hyaluronan receptor-1 (LYVE-1). The authors confirmed the presence of lymphatic endothelium in the human ciliary body. Later, these findings were confirmed by Oatts and colleagues by comparing in vitro and in vivo the uveoscleral outflow capability of two different suprachoroidal shunts [34].

Considering the suitability of the supraciliary space for decreasing IOP, surgeons have tried various techniques to exploit this pathway in the management of glaucoma. These surgeries, which are intended to enhance AH flow through the non-trabecular outflow pathway, offer many advantages, one of which is their blebless nature. It is known that one of the biggest limitations of traditional filtering glaucoma surgeries is blebs, which are related to poor cosmesis, bleb leakage, a lifetime risk for endophthalmitis, and an unpredictable wound healing response [35]. In contrast, blebless surgery reduces the risk of a flat AC and minimizes tissue trauma. Further, the absence of bleb leakage minimizes costs related to secondary surgical intervention [35,36,37]. Rerouting the AH from the AC directly to the supraciliary or SCS significantly reduces inflammation and fibrosis and consequently reduces the risk of surgical failure [34]. Another advantage is that the supraciliary space offers the surgeon two surgical approaches: ab externo and ab interno.

Various attempts have been made to exploit the uveoscelral outflow pathway in lowering IOP in glaucoma patients. SOLX Gold Shunt™ [36,37,38,39], polypropylene Aquashunt™ [34] and the STARflo™ [40] devices have been developed and popularized as blebless glaucoma surgeries to enhance the non-trabecular outflow pathway without cyclodialysis. These surgeries are variants of penetrating glaucoma surgeries. At the time of surgery, one end of the device is inserted into the AC and the other end is inserted into the SCS. Melamed et al. [38] examined thirty-eight patients with uncontrolled IOP who underwent SOLX Gold Shunt implantation with a mean follow-up period of 11.7 months. Using 20 MHz ultrasound biomicroscopy, the authors noted a spongy appearance of the sclera above the plate of the device. A mean IOP reduction of 9 mmHg was observed, going from 27.6 mmHg (baseline) to 18.2 mmHg (last follow-up). The mean number of anti-glaucoma medications also decreased from 2.0 at baseline to 1.5 at the last follow-up. Total surgical success was achieved in 79% of patients, while complete success was achieved in only 13.2%. Figus et al., in 2011 [36,39], studied the long-term efficiency and safety of this device in fifty-five patients with refractory glaucoma and a history of previous failed glaucoma surgery. At twenty-four months, complete success (defined as an IOP < 21mmHg together with a 33% reduction from baseline without any anti-glaucoma medication use) was achieved in 5.5% of the patients (3 eyes), and qualified success was achieved in 67.3% of the patients (37 eyes). Skaat [37] compared the safety and efficacy of the Gold shunt and the Ahmed® glaucoma valve. No statistically significant difference was observed in terms of IOP reduction or number of medications. In terms of safety, they reported no major operative or postoperative complications. Several studies have demonstrated that fibroblastic activation is one of the main causes of failure of these surgeries [34,41,42,43].

Several authors have attempted to improve the outcome of deep sclerectomy (DS) by combining it with an improvement in supraciliary outflow [36,44,45,46,47,48,49,50,51]. The results obtained thus far are encouraging but not definitive. DS is a non-penetrating filtering surgery. In this type of surgery, the AH leaks to the subconjunctival space to form a bleb. Perhaps the presence of a conjunctival bleb as the main filtration site for the AH did not open this pathway completely, thus affecting the final results. In our opinion, this observation is important and indicates that in order to exploit the non-trabecular outflow pathway, it is necessary to prevent leakage of AH into the subconjunctival space. Our technique fulfills both these requirements. Watertight suturing of the superficial scleral flap and the allocation of appropriate time for complete healing of the conjunctiva with the underlying tissues prevent any leakage of AH into the subconjunctival space. The collagen implant placed in the ISC and the suprachoroidal tunnel acts not only as a spacer but also as a conduit for AH. Once the conjunctiva is completely healed, the ISC is separated from the AC only by the thin inner wall of the SC. After YAG-LT, the AH flow is rerouted from the AC to the SCS exclusively.

The authors of various recent studies have published encouraging results of DS augmented with suprachoroidal drainage to increase its long-term efficacy [52,53,54,55]. Zavgorodnyaya N.G. et al. [52] carried out cyclodialysis ab interno and implanted a nondegradable biocollagen implant in the suprachoroidal cleft as a spacer to improve the results of surgical treatment of glaucoma. Surgeons operated upon 86 patients (90 eyes) and achieved significant long-term reductions in IOP. Karlova reported nearly identical favorable long-term results of non-penetrating sinusotomy in lowering IOP [23]. The authors operated upon 105 patients using a collagen implant to enhance uveoscleral outflow. Pershin KB et al. [51] compared the long-term results of surgical treatment of glaucoma by non-penetrating DS with and without suprachoroidal drainage. The authors used a nondegradable biocollagen implant. They found that hypotensive efficacy and safety were the same across groups, except that the frequency of laser goniopuncture of Descemet’s membrane was significantly lower in the group with suprachoroidal drainage.

Different biomaterials (sclera [6,7], collagen implants (Ologen and others) [4,56], synthetic materials (Teflon [57,58,59], polyethylene, or silicone, silicone elastomer (Silastic) [60], hydrogel [61], metallic devices [3,62]) have been proposed and popularized to maintain the cyclodialysis cleft. These implants can be installed by either an ab externo or ab interno approach. The results of implanting these devices were not encouraging and did not offer any additional advantage.

The role of lymphatic drainage from functional blebs after penetrating, non-penetrating and MIGS surgeries has been determined in animals and normal subjects [63,64,65,66,67,68,69,70]. Recently, it was proved that in addition to the blood circulation system, lymphatics play a significant role in the drainage of trabecular outflow [71]. Until now, it was believed that there is no direct connection between the SC, an important structure of the trabecular outflow pathway, and lymphatic vessels. Using high-resolution three-dimensional (3D) imaging technology to examine intact eyeballs, Yang Y et al. [71] reported the discovery of a new structure, which they named the ‘lymphatic bridge’, that directly connects the SC to the limbal and conjunctival lymphatic pathway. The authors also confirmed the existence of a new conjunctival lymphatic outflow pathway for AH from the AC. They performed a functional study of AC dye injection (Texas Red™ Dextran) and live imaging of AH outflow in mice using an advanced live imaging system and detected a fluorescent signal inside the Prox-1+ CLVs, which in turn challenged the traditional view of the conventional outflow pathway from the SC into the episcleral veins only, which are blood vessels. The entire conjunctival outflow pathway (SC–lymphatic bridge–limbal–CLV) was Prox-1 positive. Starting from the lymphatic bridge, all structures involved in this new pathway also expressed LYVE-1, indicating a lymphatic nature. The results of this study emphasize that the lymphatic system plays a more significant role in AH drainage than previously recognized.

Under normal conditions, the non-trabecular outflow accounts for less than 20% of the total AH outflow. The condition changes once the resistance of the ciliary muscle is bypassed and there is a multifold increase in uveoscleral outflow. It remains uncertain how nature copes with the excess fluid accumulating in the SCS. The usual pathways are inefficient at draining excessive fluid, and it becomes necessary to activate some of the hidden compensatory mechanisms to draw out this excessive fluid.

Except for a few reports on the role of lymphatics in suprachoroidal drainage to maintain post-surgical hydrodynamics [8,9,30], this question has not received proper attention. Sauntharrajan B et al. [72] used near-infrared (NIR) fluorescence imaging to detect the NIR fluorescent tracer CF770/BSA 20 minutes after suprachoroidal injection in albino mice. Suprachoroidally injected tracer was detected within podoplanin-positive CLVs in the nasal quadrant of the ipsilateral eye, with no signal observed in contralateral control eyes. The authors report that these findings indicate that CLVs participate in distal drainage of tracer from the SCS.

An interesting observation was made by Khoo et al [70]. While conducting a study to identify the etiology of persistent hypotony, these authors discovered ‘lymphatic overdrain’ as a cause of post-trabeculectomy hypotony. Khoo investigated 10 subjects with hypotony. He irrigated the ACs of these patients with a 0.1% solution of trypan blue dye and categorized the pattern of dye flow in the AC. In seven subjects with confirmed cyclodialysis clefts on gonioscopy, a preferential flow of the dye to the cleft region was noticed. Investigations of the other two subjects with post-trabeculectomy hypotony resulted in the discovery of lymphatic overdrain. In these two hypotonus subjects, the authors observed rapid, extensive lymphatic staining extending over six clock hours without visible bleb formation. The authors named it ‘lymphatic overdrain’. Both patients were female and had an IOP of 1 mmHg after glaucoma surgery. They both suffered from hypotonous maculopathy, and neither had a visible trabeculectomy bleb on standard slit lamp examination. One patient had been hypotonus for nine months, and the other for five weeks. After the dye study, the patient had undergone surgery involving dissection of the conjunctiva surrounding the lymphatic origin and dye pooling. A diathermy was applied to the area of lymphatic overdrain, with subsequent conjunctival closure. In the other patient, direct diathermy was applied to the conjunctiva surrounding the origin of the lymphatic drainage from the sclera. In both patients, the IOP normalized after surgery, with improved VA. The authors suggested that in these patients, a direct lymphatic connection to the AH entering the sclera was made beneath the surgically created scleral flap of the trabeculectomy. The lymphatic connections were responsible for removing the AH faster than it could enter the subconjunctival space and hence interrupt the formation of a subconjunctival bleb. The diathermy treatment broke the connection between lymphatics and intrascleral AH and was successful in these two patients.

In our report, sufficient clinical observations supported by OCT investigations regarding the role of scleral, episcleral and CLVs in suprachoroidal drainage are provided. Among other characteristics, it was observed that the CLVs appeared directly from the sclera at sites far from the operation site without having any relation to the surgical site. This confirms that the AH did not accumulate in the SCS at the surgical site but spread to other areas. Reaching the scleral areas rich with lymphatics, the AH leaves the SCS and passes into them and, from there, through episcleral lymphatic vessels, reaches the CLVs. There may be another explanation for this event. During surgery, some diathermy was applied to the upper layers of the sclera to make the surgical field bloodless. This could result in damage to the lymphatic vessels of this area, causing AH to seek other sites to exit the SCS.

In the present case series, clinical observations and OCT evaluation of the surgical sites confirmed the absence of FBs in all cases, indicating that applying the proposed technique enables most of the AH to flow from the AC to the SCS without being diverted to the subconjunctival space. The role of lymphatics in suprachoroidal drainage and lowering the IOP is supported by the results obtained. In more than fifty percent of cases, previously non-visible CLVs became visible biomicroscopically, indicating their involvement in AH drainage. The time of their appearance, along with their duration, number, shape, and size, differed from patient to patient. In certain cases, they appeared after surgery and in others, immediately after YAG-LT, especially in cases with a higher postoperative IOP. Observations indicate that to activate this pathway, it is essential that LT is performed only when the patient’s IOP is more than the target IOP. Our findings support the observations of Benedict O. [65], who pointed out that if after trabeculectomy the tension is too low at the surgical site, in most cases, a FB will form. If the IOP is higher than the episcleral vein pressure, new vessels (including lymphatic vessels) may develop and drain the AH from the scleral fistula, providing a good pressure-regulating effect without a bleb.

A reason for the appearance of biomicroscopic CLV in some cases, especially in patients who have undergone YAG-LT, was proposed in our previous report [9]. The results of this study further support the earlier proposed hypothesis. In living beings, the lymphatic vasculature plays an important role in regulating interstitial fluid homeostasis, as these vessels drain excess interstitial fluid. Extracellular fluid, leukocytes, proteins, and metabolites penetrate the blind permeable lymphatic capillaries to form lymph. In nature, the conjunctiva, episclera and sclera have plenty of ‘sleeping’ lymphatic vessels. Following surgery via the proposed technique and after LT, the AH enters the ISC and accumulated there under pressure, which is more than the pressure in episcleral veins. From there, AH enters the SCS, which has been made easy by implanting a CI with one end in the ISC and the other end in the suprachoroidal tunnel. The CI serves as not only a spacer but also as a conduit. As there is no leakage to the subconjunctival space, AH enters the SCS only. From there, through scleral microchannels and lymphatics, the AH leaves the SCS and enters the episcleral and CLVs. With an excessive amount of AH in their lumen, the lymphatic vessels and capillaries swell. They remain in this state if the forward lymph flow is not adequate or resistance is encountered on the flow path. The bulging of vessels with excessive AH makes them visible on slit lamp examination. With the onset of normal AH flow via these vessels, the LV became less prominent and reduced in size and number, as shown in Figure 8 a-c and Figure 9 b-d. At this stage, they are not visible on biomicroscopy, but they are identifiable on OCT. This was demonstrated in our previous reports and is proven in this report. The results obtained from this study demonstrate that the continuous flow of AH from the AC to the SCS activates a novel outflow pathway, the SCS–scleral–episcleral–CLV, to drain excess fluid from the SCS.

In this series, a biodegradable CI was used as a spacer and conduit. Many other authors used intrascleral implantation of biocompatible CI to enhance the success rate of DS and to lessen the effect of fibrosis at the surgical site [46,73,74]. These implants maintain the space in the scleral bed, provide support for the AH elimination route and act like a sponge, carrying the liquid by capillary action. Mitwally et al. [50] demonstrated a greater IOP-lowering effect of DS with suprachoroidal CI than with DS and intrascleral implantation. The role of the non-absorbable collagen implant (Xenoplast, Dubna-Biofarm, Moscow, Russia) in the SCS in decreasing IOP was studied by Shradka A.S. et al. [4]. According to these authors, Xenoplast may be implanted via an ab externo or ab interno approach. The main drawback of this implant is its coarse surface, which makes implantation traumatic to the uveal tissue, leading to fibrosis and blockage of the cyclodialysis tunnel. The implant used in the present study is thin and stiff in its dry state, with smooth surfaces, so implantation is easy and atraumatic. Notably, in the proposed technique, exposure of the uveal tissue surface for AH resorption is maximized by also incising a strip of deep scleral layers posterior to the scleral bridge. The CI placement specified for this technique plays an important role in activating the lymphatic outflow.

The proposed technique has certain advantages. All surgical steps are performed without perforating the eyeball; hence, all complications related to the sudden decrease in IOP are either minimized or completely avoided. In the proposed technique, the enhanced AH outflow occurs through the SCS–scleral–episcleral–CLV route, resembling a closed outflow system. This outflow is independent of FBs. There is no need to use antifibrotic agents to salvage and increase the lifespan of FBs or to perform needling or revision of failed blebs.

This technique has certain drawbacks as well. First, it is an ab externo procedure that requires extensive tissue dissection, resulting in surgical trauma and prolongation of surgery time. Second, it is a two-stage surgery and necessitates close monitoring of patients in the early postoperative period. Third, there is a possibility that the trabeculotomy opening will be blocked by iris tissue, resulting in an increase in IOP. A pre-, peri- or postoperative peripheral iridotomy adjacent to the area of proposed intervention avoids this complication.

A shortcoming of this study is that it is a consecutive case series without a control arm. Randomized, controlled, and comparative studies with larger groups are required to confirm the efficacy and safety of this technique.

5. Conclusions

The long-term, real-world clinical outcomes of using the proposed technique enable us to conclude that the technique is safe and effective in decreasing IOP in the long term and decreasing the medication burden; it is also bleb independent. A novel outflow route—SCS–scleral–episcleral–CLV—was identified for suprachoroidal drainage.

6. Patents

• Method to activate the uveoscleral outflow pathway of aqueous humor. Patent of the Russian Federation for invention № 2712640, granted on 30.01.2020.
• Combined method to activate different mechanisms of aqueous humor outflow in glaucoma. Patent of the Russian Federation for invention № 2766730, granted on 15.03.2022.
• Surgical method for simultaneous activation of different aqueous humor outflow pathways in glaucoma. Patent of the Russian Federation for invention № 2782126 granted on 21.10.2022.
• Method to treat open angle glaucoma. Patent of the Russian Federation for invention № 2830376, granted on 18.11.2024.
• Method to activate the conventional and non-conventional outflow pathways of aqueous humor in glaucoma. Patent of the Russian Federation for invention № 2833766, granted on 28.01.2025.