Surgical Outcomes of Visco-Circumferential-Suture-Trabeculotomy Versus Rigid Probe Trabeculotomy in Primary Congenital Glaucoma: A 3-Year Randomized Controlled Study

Purpose: The aim was to compare the long-term surgical outcomes of visco-circumferential-suture-trabeculotomy (VCST) and rigid probe viscotrabeculotomy (VT) in patients with primary congenital glaucoma (PCG). Patients and Methods: The study was conducted on 84 (47 right) eyes of 49 (32 males) children PCG to the pediatric ophthalmology unit of Mansoura Ophthalmic Center of Mansoura University, Egypt between 2015 and 2018. An initial office examination was followed by an examination under general anesthesia to establish the diagnosis of PCG. The children were then scheduled for surgery and the eyes randomly assigned to VCST or VT. Follow-up visits were scheduled at the first day, first week, first, and third months and then every 3 months for 1 year. Results: The mean±SD age of the study children at presentation was 4.8±2.1 and 4.9±1.7 months in the VCST and the VT groups, respectively (P=0.827). The mean±SD preoperative intraocular pressure (IOP) was 29.13±3.3 and 29.89±3.2 mm Hg in the VCST and VT groups, respectively (P=0.292) and 11.9±1.3 and 13.8±1.2 mm Hg at the end of 36 moths of follow-up (P<0.001). The IOP at all follow-up time points (except at the third month, P=0.924) was statistically significantly less in the VCST group than in the VT group (at week 1, month 1, 6, 9, 12, 18, 24, 30, and 36 the P<0.001). The cumulative probability of success was 100%, 95%, 90%, and 90%, respectively in VSCT and 100%, 72.7%, 97.7%, 90.9%, and 84% in VT at 12, 24, 30, and 36 months. Conclusions: Both VCST and VT were effective and safe for lowering the IOP in PCG with VCST providing a marginal advantage over VT.

P rimary congenital glaucoma (PCG) is an uncommon anterior chamber (AC) angle dysgenesis, accounting for 18% of childhood blindness. 1 It reveals itself within the first years of life with elevated intraocular pressure (IOP), enlarged hazy cornea, and cupping of the optic disc. Surgery remains the mainstay of treatment of PCG. 2 Trabeculotomy ab externo is an angle surgery performed in children with hazy cornea precluding goniotomy and enjoys success rates that range from 73% 3 to 90%. 4 Trabeculotomy ab externo techniques include conventional metal probe trabeculotomy, viscotrabeculotomy (VT), 5 360-degree suture trabeculotomy 6 and trabeculotomy with the use of illuminated microcatheter which has the advantage of easy identification and cannulation of Schlemm canal (SC). 7 With the introduction of 360-degree trabeculotomy using a polypropylene suture, the success rates reported ranged from 87% to 93%. 7,8 Metal probe cannot achieve circumferential trabeculotomy. The main disadvantage of 360 degrees suture trabeculotomy is the relative difficulty in identification of SC and the potential risk of false passages in some reported cases leading to an inadvertent misdirection into the suprachoroidal and subretinal space. 9 Although the illuminated microcatheter helps to identify and cannulate SC, its cost constitutes a financial burden that maybe potentially unaffordable in many places of the World. VT is a modified method of probe trabeculotomy in which a viscoelastic is used to enhance the success of the procedure by separating tissues and preventing bleeding and fibroblastic proliferation at the trabeculotomy opening. VT was proved to be more effective than conventional probe trabeculotomy for reduction of IOP in PCG with more stability, higher success rates, and lower complications. 5 In order to combine the advantages of the use of ophthalmic viscosurgical devices and those of circumferential trabeculotomy without the need for an illuminated microcatheter, the authors suggest this technique (Visco-Circumferential-Suture-Trabeculotomy "VCST"). The authors hypothesize that the injection of a viscoelastic into both ends of the unroofed SC before its cannulation by a polypropylene suture and subsequent circumferential trabeculotomy may facilitate circumferential cannulation of SC and hence the trabeculotomy and increase the success of the technique. The aim of the present study was to compare the long-term surgical outcomes of this proposed technique (VCST) and rigid probe VT in patients with PCG.

PATIENTS AND METHODS
The study was conducted on children below the age of 2 years presenting with PCG to the Pediatric Ophthalmology Unit of Mansoura Ophthalmic Center of Mansoura University, Egypt between January 2015 and February 2018. The DOI: 10.1097/IJG.0000000000001944 study was granted approval by the Ethics Committee of the Faculty of Medicine of Mansoura University and followed the tenets of the Declaration of Helsinki. Written informed consent for participation in the study was obtained from all children' care providers after a clear explanation of the surgical procedures and their possible consequences. After taking a full history from the care providers of the study children, an initial office examination was followed by an examination under general anesthesia (GA) using inhalational sevoflorane (fluoromethyl hexafluoroisopropyl ether) anesthesia. All examinations were conducted by the same ophthalmologist (A.S.E.) and followed a standard protocol which was previously described by the authors. 5 Perkin's handheld applanation tonometer (Haag Streit USA and Reliance Medical Products, Mason, OH) was used for IOP measurement with the eyes central just after the induction of GA. Because of the known effect of inhalational GA of IOP reduction, if PCG was suspected with a low measured IOP, serial follow-ups were scheduled to monitor progression of corneal diameter, axial length, and optic disc cupping to establish the diagnosis of PCG. The children were then scheduled for surgery and the eyes randomly assigned (using simple randomization by flipping a coin) for the procedure of "Visco-Circumferential Suture Trabeculotomy" (VCST) or "Viscotrabeculotomy" (VT). In children suffering bilateral PCG, randomization (to either VCST or VT) was applied to the first operated eye while the fellow eye was automatically assigned to the other procedure and included in the study. All surgeries were conducted by a single surgeon (A.S.E.).

VCST
Exposure of the operative field through a corneal traction suture (vicryl 6/0) placed superiorly was followed by a superior limbal-based conjunctival flap and a paracentesis. After adequate hemostasis, a superficial rectangular scleral flap 4×4 mm was fashioned and dissected forward toward the limbus. A deep sceral flap (2×2 mm) was then created toward the limbus underneath the superficial flap exposing the scleral spur and deroofing SC. Viscoelastic (Healon GV, Pfizer, NY) was gradually injected (using a standard 30 G viscocanalostomy cannula) into the ostia of SC (dilate SC and facilitate suture progression into the canal). Then, the 5/0 polypropylene suture tip was cauterized into a blunt tip (to ensure atraumatic probing of SC). The tip was inserted into the left ostium of SC using a microsurgical forceps and advanced through the whole circumference of the canal. When the tip presented to the right ostium the AC was filled with a viscoelastic through the paracentesis and traction was applied to approximate both ends of the 5/0 polypropylene suture, thus creating a visco-360-degree trabeculotomy. Eyes in which the 360-degree suture trabeculotomy failed (7 eyes) were excluded from the study (and the surgery completed as a VT). Surgery was concluded by closure of the scleral flap and the overlying conjunctiva by 10/0 nylon sutures.

VT
The surgical technique of VT was previously described in details. 5 Postoperative treatment included topical ofloxacin and dexamethasone 5 times daily with gradual tapering over 4 weeks. Timolol and Dorzolamide drops were administered twice daily whenever needed (IOP spikes). Follow-up visits were scheduled at the first day, first week, first month, third month, and then every 3 months for the first year then every 6 months for 3 years. Day 1 examination was performed to detect any early postoperative complications and was performed in the office with the child held on the mother's lap. Postoperative examinations followed the same protocol as the preoperative examinations.
Complete success was defined as an IOP < 16 mm Hg without IOP-lowering medications or further surgical interventions, without any sign of glaucoma progression (increasing corneal diameter, axial length, or cup/disc ratio) and without visual devastating complications. Qualified success was defined as fulfilling the same criteria but with the use of IOP-lowering medications. When any surgical intervention was required during the follow-up period, it was done without delay and this particular eye was excluded from the data analysis of the study from that specific follow-up time point to the rest of the follow-up and calculated as a failure.
Data was analyzed with IBM SPSS version 20. Repeated measure analysis of variance and paired t tests were used to compare between the preoperative and postoperative variables in each group. The comparison between the 2 groups was done by independent samples t test for numerical variables and χ 2 test for categorical variables. The Fisher exact P-values were chosen where there was an expected count of < 5. Kaplan-Meier survival curves were plotted to estimate the mean survival time and probabilities of failure at different follow-up stages in the both groups. For all tests, a P-value of < 0.05 was considered significant.

RESULTS
The study was conducted on 84 (47 right) eyes of 49 (32 males) children presenting with and operated upon for PCG in Mansoura Ophthalmic Center of Mansoura University in Mansoura, Egypt. The demographic characteristics and presenting features of the study children are presented in Table 1. The mean ± SD age of the study children at presentation was 4.8 ± 2.1 and 4.9 ± 1.7 months in the VCST and the VT groups, respectively (P = 0.827). There were no statistically significant differences in the demographic characteristics between the study children in the 2 study groups. The preoperative clinical characteristics of the study eyes are presented in Table 2. There were no statistically significant differences in the preoperative clinical characteristics between the study eyes in the 2 study groups (for the IOP, corneal diameter, C/D ratio, axial length and IOP-lowering medications P was 0.292, 0.265, 0.633, 0.739, and 0.681). The intraocular pressure (IOP) data at different follow-up time points in both groups are presented in Table 3 and Figure 1. There was a statistically significant reduction of the IOP from the preoperative values at all follow-up time points in both study groups (P < 0.001 at all-time points in both groups). The IOP at all follow-up time points (except at the third month, P = 0.924) was statistically significantly less in the VCST group than in the VT group (at week 1, month 1, month 6, month 9, month 12, month 18, month 24, month 30, and month 36 the P was 0.0002, 0.014, 0.0005, < 0.001, < 0.001, < 0.001, 0.0003, 0.0003, < 0.001) (data for 2 eyes from the 30th month onwards in the VCST and for 3 eyes from the 24th month onwards in the VT groups, respectively, were not available, lost for follow-up). The mean ± SD (range) of the corneal diameter, cup/disc ratio and axial length  Table 4 and the Kaplan-Meier curve is presented in Figure 2. There was no statistically significant difference between the 2 study groups in the success rates (P = 0.278). The cumulative probability of success was 100%, 95%, 90%, and 90%, respectively, in VSCT, and 100%, 72.7%, 97.7%, 90.9%, and 84% in VT at 12, 24, 30, and 36 months. The mean ± SD survival time (period of time expected before failure occurs) was 35 ± 0.45 months in VSCT group and 35.3 ± 0.37 months in VT group (P = 0.462; log Rank (Mantel Cox test). The Kaplan-Meier survival curve is presented in Figure 2. The complications in the study eyes are presented in Table 5.  VCST indicates visco-circumferential-suture-trabeculotomy; VT, viscotrabeculotomy. VCST indicates visco-circumferential-suture-trabeculotomy; VT, viscotrabeculotomy.

DISCUSSION
The study was conducted on 84 eyes of 49 children presenting with PCG in the first 2 years of life and compared the results of VCST to conventional VT. Both procedures brought about successful control of IOP in operated eyes with a marginal advantage for VCST over VT. Studying the demographics of the study population demonstrates the already established norms of PCG; namely male predominance, 10 the bilaterality of the disease process 11 and the presentation in the first 6 months of life. 12 Almost half of the study children were born to consanguineous parents hence emphasizing the role of heredity and consanguinity in PCG, as already reported. 13 The young age of the parents at conception negates any relation to the incriminated chromosomal abnormality and the low incidence of family history and affected siblings among study children may be related to the reported recessive inheritance and incomplete penetrance in PCG. 14 There were no statistically significant differences between the 2 study groups in the patient demographics highlighting the homogeneity of the sample and adding to the strength of the study findings.
Scrutiny of the clinical characteristics of the study eyes reveals important insights. The fact that the most common presenting symptom was a hazy cornea is in line with published reports about the PCG in Egypt 13 and the Middle East. 15 The presenting IOP, C/D ratio and axial length is in accordance with other published studies 16 and the IOP-lowering medications used preoperatively were a temporizing measure preoperatively modeling their standard role in PCG. 4 Tracing the IOP at the follow-up time points highlights the salient finding of the study; both surgical approaches were effective in bringing about a significant reduction of IOP at all follow time points, with an obvious marginal advantage for VCST over VT. The IOP trend in both techniques is that of an initial significant reduction followed by a gradual progressive minimal elevation over the 3 years study period. Although this IOP elevation at the conclusion of the 3-year study period remains clearly successful and reasonably low, the lifelong significance of this trend remains speculative. This IOP reduction brought about by VCST is clearly greater than that reported for conventional suture trabeculotomy 17 and comparable to that brought about by circumferential trabeculotomy by the illuminated microcatheter (and viscoelastic). 18 The IOP outcome in the VT group reported in this study is comparable to that reported for VT by the authors in other studies. 5 The success rates reported in this study emphasize the fact that angle surgery is highly successful in controlling IOP in PCG. An advantage for VCST over VT is exemplified by the higher success rates, and more so; the higher percentage of complete success (with less dependence on IOP-lowering medications in the VCST group than in the VT group), though not statistically significant. The most common complication encountered in this study was a minimal self-limiting hyphema, a reflection of the valveless SC-Collector Channels system with regurge of blood into the eye upon lowering the IOP. This complication parallels other published reports. 19 The localized FIGURE 1. Intraocular pressure (IOP) of study eyes at different follow-up time points. There were 2 dropouts from the 30th month onwards in the visco-circumferential-suture-trabeculotomy (VCST) group and 3 dropouts from the 24th month onwards in the viscotrabeculotomy (VT) group. There was a statistically significant reduction of the IOP from the preoperative values at all follow-up time points in both study groups (P < 0.001 at all-time points in both groups). The IOP at all follow-up time points (except at the third month, P = 0.924) was statistically significantly less in the VCST group than in the VT group (at week 1, month 1, month 6, month 9, month 12, month 18, month 24, month 30, and month 36 the P was 0.0002, 0.014, 0.0005, < 0.001, < 0.001, < 0.001, 0.0003, 0.0003, < 0.001). Figure 1 can be viewed in color online at www.glaucomajournal.com. Descemet detachment is obviously accidental during the sweep into the AC and is already reported by the authors in previous publications. 20 This study has limitations. The relatively short follow-up period in view of the trend of a rising IOP over time poses concerns on the longer term outcome of the both procedures. Assessment of visual function in the study children would have provided useful information on the functional outcome of both procedures. However, given the study was initiated at a relatively young age and concluded when the study children were still preverbal and given that the main focus of the study was the IOP outcome, the authors did not report on the visual function of the study children, though assessed and managed as part of the therapeutic services provided at the study center to patients.
To conclude, both VCST and VT were effective and safe for lowering the IOP in PCG with VCST providing a marginal advantage over VT. VCST offers the potential advantages of combining the efficacy of 360 degrees circumferential trabeculotomy with relatively low cost using the prolene suture with the facilitation of the SC cannulation and dilatation provided by the use of the ophthalmic viscosurgical device.