Safety and Efficacy of Scleral Concave Pool Trabeculectomy Combined Phacoemulsification for Eyes with Coexisting Cataract and Primary Open Angle Glaucoma. CURRENT STATUS:

Purpose To investigate the safety and efficacy of trabeculectomy (SCPT) combined phacoemulsification for eyes with coexisting cataract and primary open angle glaucoma (POAG). Methods This was a retrospective, controlled, interventional case series. Thirty patients (30 eyes) were diagnosed with coexisting cataract and POAG between May 2015 and April 2018. Fourteen eyes underwent SCPT combined phacoemulsification were set as the study group, and 16 eyes received conventional phacotrabeculectomy were set as the control group. All patients were followed up for at least 6 months. The preoperative to postoperative changes in IOP, glaucoma medication requirements, BCVA, blebs functions, and adverse events were recorded. Results The groups were matched for baseline age, BCVA, IOP and types of IOP-lowering medications (all P>0.05). At 6-month visit, there were no significant difference between control and study group in the improvement of BCVA (0.22±0.24 versus 0.18±0.26, P=0.718), reduction of IOP (-11.21±8.61mmHg versus -9.19±9.18mmHg, P=0.540) and the number of eyes that needed IOP-lowering medications (2 versus 3, P=0.743). At the last visit, the rate of forming functioning blebs was significantly different between the study and control groups, (92.9% versus 68.7% respectively, P=0.007). In the study group, 5 eyes developed shallow anterior chamber,and 1 eye showed limited choroidal detachment, whereas in the control group 1 eye developed malignant glaucoma. All adverse events were successfully managed. Conclusion The SCPT combined phacoemulsification is a safe and effective alternative to conventional phacotrabeculectomy for patients with POAG and


Introduction
Fibroblast proliferation and collagen deposition at filter channel is the most common reason for trabeculectomy failure [1][2][3] . It is widely accepted that the application of adjunctive antifibrotic agents such as 5-fluorouracil (5-FU) and mitomycin C (MMC) can enhance the success rate of filtration surgery [4,5] . However, the inavailability of adjunctive antifibrotic agents such as 5-FU and MMC in China sparks an emergency requirement for the improvement of trabeculectomy technique.
Improvement of techniques, such as deep sclerectomy (DS) and CO 2 laser-assisted sclerectomy surgery (CLASS) has reduced the complication rates in treating open angle glaucoma [6][7][8] . Contrary to trabeculectomy, DS, which does not require penetrating the anterior chamber, has been reported to improve the safety of glaucoma surgery with high success rate, but it requires considerable technical skills to preserve the integrity of the trabeculo-Descemet's membrane (TDM) [6,9] .
Recently, a newly developed technique, CLASS, which performs deep sclerectomy down to the TDM by CO 2 laser application on the scleral bed after a half thickness scleral flap is created, has been reported as a feasible and apparently safe procedure [8,10] . However, the IOPtiMate system used in the CLASS procedure is too expensive for its wide spread application in developing countries such as China.
Furthermore, CLASS technique is a non-penetrating technique which requires a long learning curve.
To our knowledge, a reservoir in the CLASS procedure allowing the percolated aqueous accumulation may help strike a balance between the production and outflow of aqueous humor, which has the advantages of keeping the filtering path unobstructed. Therefore,we developed a penetrating surgery technique to add a scleral concave pool manually in the trabeculectomy procedure which needs shorter learning curve than non-penetrating technique. In our retrospective study, we aimed to investigate the safety and efficacy of scleral concave pool trabeculectomy surgery (SCPT), performed in conjunction with phacoemulsification, for treating eyes with coexisting cataract and primary open angle glaucoma. Methods 6 explanation of the nature of the procedure.
In both groups, all surgery procedures were performed under peribulbar anesthesia.
Before filtration surgeries, phacoemulsification and intraocular lens implantation were performed. A fornix-based conjunctival flap was dissected in the superior quadrant, and the sclera was exposed. A 4×4mm limbus-based scleral flap was then created. For the SCPT procedure, a reservoir measuring about 3×2mm was created over the posterior scleral bed by a surgical blade (Fig. 1). The deeper sclera and the root of Schlemm canal were excised through a convex groove. The superficial scleral flap was closed with 10-0 nylon sutures, and the conjunctival wound was sutured with 10-0 nylon sutures. For the conventional phacotrabeculectomy, no reservoir was further performed. The superficial scleral flap and the conjunctival wound were sutured straightly through the same way with 10-0 nylon sutures.
Postoperative management in both groups included overnight patching, topical levofloxacin 5 mg/ml and dexamethasone 1 mg/ml for 4 weeks. Glaucoma medications were administered if necessary.
Demographics, systemic diseases, ophthalmic history, topical and systemic medications before the operation were collected. Ocular examinations conducted at baseline and at each follow-up visit (1 day, 1week, 1 month and 6 months) including best corrected visual acuity (BCVA) with Snellen chart, Goldmann applanation tonometry, slit-lamp examination, gonioscopy, and fundus examination were reviewed. Filtering blebs were categorized as 4 types according to the Kronfeld's classification [11] . In brief, thin and polycystic blebs with transconjunctival flow of fluid were classified as Type I bleb, other flatter, thicker, and more diffuse blebs with a relatively vascular appearance as Type II bleb, failed bleb in which conjunctiva is scarred to underlying episclera as Type III bleb, and encapsulated bleb with characteristic vascular, dome-shaped, cyst-like appearance as Type IV bleb. Procedure related complications and number of intraocular pressure (IOP) lowering medications administrated postoperatively were recorded.

Data analysis
Data were first tested for normality using Sample K-S test. Variable confirming to normal distribution were summarized as means ± standard deviation (SD) except when stated otherwise. Comparisons of normally distributed variables between the groups were conducted using independent samples t test, or with nonparametric test if variables are not normally distributed. Changes in BCVA and IOP from baseline to four follow-up visits between the 2 groups were examined using a repeated measure ANOVA. The number of functioning blebs between the two groups at each visit was compared using Mann-Whitney U test. Statistical analysis was performed using SPSS Version 16.0 (SPSS 16.0, Inc., Chicago, IL). Significance was determined as P<0.05 at two tails.

Results
As shown in Table 1, there was no significant difference in the mean baseline age, gender, BCVA, IOP and number of IOP-lowering medications used between the two groups (all P > 0.05). Compared to baseline, postoperative BCVA significantly improved at 1-week, 1-month and 6-month visit in both groups (all P < 0.05) (Fig. 2).
There was no significant difference in the magnitude of visual improvement at each visit between the 2 groups (all P > 0.05) (Fig. 2).

Discussion
In the current study, SCPT combined phacoemulsification was comparable to conventional phacotrabeculectomy in terms of lowered IOP and reduced number of medications over the first 6-month period but has higher rate of forming functional blebs. Patient undergoing SCPT combined phacoemulsification may be easier to develop a shallow anterior chamber in the early stage, but it could recover after some appropriate management. To the best of our knowledge, we are one of the few in making this new improvement in filtering surgery and comparing its safety and efficacy to conventional phacotrabeculectomy, which is the gold standard technique in open-angle glaucoma [12] .
Lowering of IOP remains the main therapeutic strategy in the treatment of glaucoma, and trabeculectomy is the most widely applied filtration surgical procedure for achieving a target IOP, with up to 90% of long term success to maintain vision-related quality of life [13][14][15] . The main purpose of filtration surgery is to lower the IOP by creating a path for more efficient drainage of the aqueous humor from the anterior chamber to the subconjunctival space. Therefore, maintaining the filtering path unobstructed is of critical importance.
However,trabeculectomies are often complicated with wound healing, postoperative fibrosis, and production of inflammatory mediators which cause bleb failure and subsequent closure of the filtering route [3,16] . 5-minute exposures of Mitomycin C during the procedure was insufficient in preventing the closure of filtering route and the failures of long term control of IOP due to the subconjunctival and scleral fibroblast proliferation [17] .
In the current study, both procedures had similar effects on reducing IOP and the number of medications used over the 6-month follow-up period, but both the complete (85.70% vs. 68.75%, P = 0.027) and qualified success rate (100.00% vs. 87.50%, P < 0.01) were significantly higher in the study group compared to the control group. In terms of blebs, the rate of forming functioning blebs in the study group was also significantly higher than that in the control group (92.9% vs. 68.7%, P = 0.007). All these results may suggest a better efficacy for the long term reduction in IOP during the procedure of SCPT combined phacoemulsification compared to conventional phacotrabeculectomy, but further work is needed to confirm the increased efficacy by reviewing long term follow up.
SCPT, as a conventional filtering surgery, have some unavoidable early complications such as postoperative anterior chamber inflammation [18] , bleb leaks [19] , intraocular hypotension [20] , and choroidal effusion etc [21] all may threaten the VA. In the current study, both surgery procedures had similar effects on the improvement of postoperative VA, even though the postoperative complications were different between them. At 2 weeks post conventional phacotrabeculectomy, 1 eye developed malignant glaucoma, which was successfully managed with some appropriate treatment. Post SCPT combined phacoemulsification, 5 eyes developed shallow anterior chamber, but all of them were successfully managed by appropriate intervention. To our knowledge, the reservoir formed in the SCPT procedure would absorb aqueous humors immediately in the early period post operation, which may be the main reason for the tendency of developing shallow anterior chamber, but when the reservoir was successfully filled with aqueous humor for a longer period of time post-surgery or after some appropriate management, the rate of developing shallow anterior chamber could be reduced. Overall, this modification of conventional filtering surgery seemed to be as safe as the conventional phacotrabeculectomy at least over the early 6-month period, but its long-term safety still warrants investigation by further studies.
The CLASS procedure, which showed a similar qualified success rate and reduction in medications compared to conventional trabeculectomy, may be an alternative to trabeculectomy when considering the postoperative complications [8,10,22,23] .
During the CLASS procedure, a reservoir is formed by using the CO 2 laser to ablate the scleral tissue [8] . To our knowledge, a reservoir allowing the percolated aqueous accumulation may have the advantage of keeping the filtering path unobstructed by the following pathways: 1) Filling the bleb with aqueous humor all the time which then help maintain the tension of bleb; 2) Help regulate the flow of liquids so that when the flow speed is low in the drainage, the accumulated aqueous humor in the reservoir can offer a replenishment of liquid; 3) Keeping the path filled with liquid flow can help wash away inflammatory factors. The CO2 laser, which can be largely absorbed by water, has little direct effect on the angle tissue when the aqueous starts to percolate [8,10] , However, the IOPtiMate system used in the CLASS procedure is too expensive for its wide spread application in developing countries such as China. Thus, by adopting the advantage of the CLASS procedure, we decided to manually create the reservoir by surgical blade during the filtering surgery. This procedure needs considerable technical skills, but all the surgery procedures were conducted by one experienced surgeon which could help reduce bias of the result.
according to previous studies, CLASS, as a nonpenetrating filtration surgery, may be an alternative to trabeculectomy, especially at the earlier glaucoma stage, considering its more attractive complications profile. However, CLASS is less effective than trabeculectomy and cannot be applied to many conditions such as the primary narrow and occludable angles or secondary glaucoma with the presence of peripheral anterior synechia [8,10] . However, according to the result of this study, by adopting the advantages of CLASS to penetration filtration surgery, SCPT combined phacoemulsification has comparable or even superior efficiency in reducing the IOP than conventional phacotrabeculectomy.
There were some limitations in this study. Firstly, the sample size was relative small, but it may be unsuited to conduct this procedure for too many patients at this stage since it is a new, untested technique. Furthermore, the follow-up time was relative short, but its short-term efficacy and safety which was the main purpose of this study could provide some positive implication for its long-term investigation. Finally, the procedure of SCPT may require considerable technical skills to form a reservoir by surgical blade, but it could be conquered by more practice.
In conclusion, by applying the advantage of CLASS to conventional trabeculectomy, SCPT combined phacoemulsification showed a similar efficacy in reducing IOP Not applicable.

-Availability of data and materials
Data and material was presented in the additional supporting files.

-Competing interests
The authors declare that they have no competing interests.

-Funding
This work was supported by no grants.  Change in BCVA post operation in both groups. *: p-value was less than 0.05 from baseline.

Figure 3
Change in IOP post operation in both groups. *: p-value was less than 0.05 from baseline.

Supplementary Files
This is a list of supplementary files associated with the primary manuscript. Click to download.

Figure 2
Change in BCVA post operation in both groups. *: p-value was less than 0.05 from baseline.

Figure 3
Change in IOP post operation in both groups. *: p-value was less than 0.05 from baseline.

Supplementary Files
This is a list of supplementary files associated with the primary manuscript. Click to download.
Additional supporting files.xlsx