Yang Cao, Hai-Shuang Lin, Hui-Yan Mao, Yin Zhao, Yan-Qian Xie, Shao-Dan Zhang, Qi Zhang, Pei-Juan Wang, Guo-Xing Li, Ai-Wu Fang, Yuan-Bo Liang

1The Eye Hospital, School of Ophthalmology and Optometry,Wenzhou Medical University, Wenzhou 325027, Zhejiang Province, China

2Glaucoma Research Institute, Wenzhou Medical University,Wenzhou 325027, Zhejiang Province, China

3National Clinical Research Center for Ocular Diseases,Wenzhou 325027, Zhejiang Province, China

Abstract

● KEYWORDS: glaucoma; internal filtration surgery;inpatient; trend

According to a report published by the Lancet Global Health Commission on Global Eye Health named Vision Beyond 2020, glaucoma is one of the leading causes of visual impairment in adults[1], as it accounts for 2% of visual impairment and 8% of blindness in the world[2]. Currently,the most effective treatment for glaucoma is reducing the intraocular pressure (IOP), as elevated IOP is a major risk factor for development and progression of glaucoma[3]. In terms of treatment, surgery is amongst the main options[4].

Trabeculectomy (Trab) and tube shunt surgery are two common, longstanding procedures that are successful in the treatment of glaucoma[5]. Whilst they can effectively reduce IOP, there remains a risk of potentially vision-threatening complications in 39% of Trab cases and in 22% of tube shunt cases; moreover, urgent postoperative interventions are necessary in 74% of Trab and 27% of tube shunts[6]. The blebrelated complications experienced by patients can be longterm, regardless of the IOP being controlled after surgery.

In recent years, there has been an increase in the treatment options available for patients with glaucoma, particularly as new surgical devices and techniques have been optimised and introduced. Phacoemulsification (Phaco) is a well-developed technique to extract cataracts and has also been performed to manage primary angle-closure glaucoma (PACG)[7]. Nevertheless,not all PACG patients in clinic are eligible for Phaco,especially those who have more than 180-degree angle closure.Therefore, goniosynechialysis (GSL) has been performed on patients with extensive angle closure who underwent Phaco,as this can lower the IOP by separating the anterior synechia from the trabecular meshwork[8-9]. Less invasive glaucoma procedures, collectively termed minimally invasive glaucoma surgery, can reduce the IOP with minimal tissue destruction,and also maintain a relatively high safety profile, short surgery time, the use of simple instrumentation, and rapid recovery for patients[10]. Non-penetrating glaucoma surgery options, such as canaloplasty and trabeculotomy, are a recent trend in clinical application[11]. These surgeries can reconstruct natural aqueous outflow channels by dilating Schlemm’s canal, thus avoiding conjunctival scarring[12]. Penetrating canaloplasty (PCP) is a new bleb-independent surgery, and has the ability to reduce IOP with a particularly high success rate in PACG[13]and traumatic angle recession glaucoma[14].

Many countries have experienced changes in glaucoma surgery trends over recent years. In Australia, the percentage of primary filtering surgery declined by 68% between 1994 and 2014[15], whilst in Japan, external filtering surgery was the most common procedure for glaucoma prior to 2017, but this was overtaken by trabeculotomy from 2018 onwards[16]. Now, blebindependent surgery has started to become the main interest of glaucoma surgeons. Wenzhou, an economically developed city in the southeast part of Zhejiang Province, has a population of over 9.5 million. The Eye Hospital of Wenzhou Medical University is one of the few tertiary hospitals in the region that specialises in ophthalmology, and has a high caseload of glaucoma inpatients. Therefore, this study in the Eye Hospital of Wenzhou Medical University analyse the trend of internal filtration surgeries between 2015 and 2021.

Ethical ApprovalThis study adhered to the Declaration of Helsinki and the study protocol was approved by the Ethics Committee of the Wenzhou Medical University prior to study commencement (Number: 2022-111-K-85). Informed consent was not required, as data were collected in de-identified fashion.Population and ProceduresAs this was a retrospective study, clinical records were obtained from the hospital’s electronic medical record system (Thiseye, Eye Care System,Versions 2022.4.14.24461) for the period of January 1, 2015,until December 31, 2021.

The inclusion criteria of this study included patients who had been diagnosed with glaucoma and had received anti-glaucoma surgery during their hospitalisation. The exclusion criteria included patients who had received paracentesis, anterior chamber irrigation, air injection to the anterior chamber,glaucoma drainage device adjustment or extraction, injection of viscoelastic agent, intravitreal injection, iriplasty, scleral allograft or coreoplasty alone. Demographic information was also obtained, such as gender, age, the type of glaucoma, and the surgeries received.

ClassificationThe types of glaucoma were classified as follows: 1) PACG: primary acute or chronic angle-closure glaucoma, primary angle closure; 2) primary open angle glaucoma (POAG): POAG and normal tension glaucoma;3) paediatric glaucoma: congenital, childhood, and juvenile glaucoma; 4) secondary glaucoma: steroid-induced glaucoma,exfoliative glaucoma, angle recession glaucoma, pigmentary glaucoma, malignant glaucoma, neovascular glaucoma, Posner-Schlossman Syndrome, iridocorneal endothelial syndrome,nanophthalmic, Sturger-Weber syndrome, uveitis and other causes lead to the glaucoma[17]; 5) reoperation: patients who had previously undergone anti-glaucoma surgery and had now been readmitted for surgery; 6) others: where classification could not be determined based on the medical records.

The surgeries were classified as follows: 1) internal filtration surgery[18]: promoting aqueous humor outflow through physiological channels (including angle surgery and suprachoroidal drainage), which was independent of bleb,including trabeculotomy, Phaco, canaloplasty, goniotomy,peripheral iridectomy, GSL, PCP, cataract extraction combined with GSL/PCP, and other similar types; 2) external filtration surgery[19]: based on the Trab and glaucoma drainage implant(GDI), including non-penetrating trabecular surgery, Ahmed,Ex-Press, XEN implantation, cataract extraction combined with Trab/GDI and so on; 3) cyclodestruction surgery:cyclophotocoagulation, low dose laser cystoplasty, ultrasound cystoplasty; 4) bleb-management surgery that was present only in the reoperation group, including bleb revision, bleb separation, conjunctival suture.

Statistical AnalysisThe glaucoma types and surgical procedures were analysed using R (Version 4.1.2) and Prism 9 (Version 9.0.0, GraphPad Software Ink). Non-normal distribution variables were represented by the median and quartiles. The Cochrane-Armitage trend test was performed to determine the trend of glaucoma surgical procedures over a period of time. Statistical significance was denoted atP＜0.05.

This study comprised 6543 (8435 eyes) patients with glaucoma who had received anti-glaucoma surgeries in the Glaucoma Department of the Eye Hospital of Wenzhou Medical University. The median age of the sample was 63 years old,with a minimum value of 1mo and a maximum value of 95 years old. Of the total sample, 2749 patients were men and 3794 patients were women (42.01%vs57.99%). These findings are shown in Table 1. The number of hospitalised patients in the Glaucoma Department exhibited an increase of 82.58% in 2021 from 2015.

Table 2 presented the number of surgeries for each type of glaucoma. PACG cases accounted for 54.00% of the hospitalised patients who received anti-glaucoma surgeries,followed by secondary glaucoma patients (15.05%), POAG patients (13.28%), and paediatric glaucoma patients (1.74%).Table 3 demonstrated the number of glaucoma surgeries performed at the Eye Hospital of Wenzhou Medical University between 2015 and 2021. The most common surgery was Phaco combined with GSL (Phaco-GSL), which accounted for 37.10% of glaucoma surgeries over the last seven years. The second most common surgery was Phaco or Phaco combined with intraocular lens implantation. Meanwhile, the proportion of GDI surgeries decreased from 7.88% in 2015 to 4.16% in 2021, while the proportion of PCP increased from 1.70% to 11.92% over this time period. The proportion of combined cataract extraction with PCP/goniotomy also increased from 0.85% to 2.81%, while combined cataract extraction with Trab/GDI witnessed a decrease in proportion from 15.34% to 9.72%. The proportion of Trab surgeries decreased between 2016-2018, but then increased slightly the following years. The proportion of cyclodestruction surgeries remained consistent over the entire time period.

The number and types of glaucoma surgeries for each type of glaucoma were shown in Table 4. The proportion of external filtration surgeries for PACG decreased from 26.10%to 15.40% from 2015 to 2021. However, the proportion of internal filtration surgeries fluctuated between 71.70% and 81.90% over this time. The angle-closure glaucoma group showed the highest proportion of internal filtration surgeries,accounting for over 70.00% of the total surgeries for this group, with a fairly consistent, statistically significant trend over the study time period (Z=2.46,P=0.014; Figure 1A).Meanwhile, the proportion of cyclodestruction surgeries remained stable without evident change between 2015 and 2021.

In 2015, the most common surgical procedure was external filtration (71.50%), while internal filtration surgery accounted for only 27.40% of surgeries in POAG patients. Yet, by 2021,this had increased to 54.40% of total surgeries for this group,whereas external filtration surgery decreased to 44.20%. The increase in internal filtration surgery over the seven-year period was found to be statistically significant (Z=6.41,P＜0.001;Figure 1B).

Table 1 Age and gender for glaucoma patients undergoing antiglaucoma surgery in the Eye Hospital of Wenzhou Medical University from 2015 to 2021

The number of surgeries performed for secondary glaucoma cases was second to angle-closure glaucoma surgeries between 2015 and 2021. The proportion of internal filtration surgeries increased from 18.20% in 2015 to a peak prevalence in 2018 of 50.00%, before fluctuating for the remaining time period, as depicted in Figure 1C (Z=5.91,P＜0.001). In contrast, external filtration surgeries exhibited the opposite trend, whereby the proportion decreased from 49.6% in 2015 to 39.00% in 2021. Cyclodestruction surgeries remained generally stable,accounting for 25.00% of total surgeries.

For paediatric glaucoma patients, the number of surgeries increased by 537.50% from 2015 to 2021, thus indicating a significant trend over this period. However, external filtration surgeries decreased from a peak proportion of 50.00% in 2015 to 9.80% in 2021, whilst the volume of internal filtration surgeries increased by 50.70%. This trend is displayed in Figure 1D (Z=5.17,P＜0.001). In addition, there were too few cyclodestruction surgeries to determine a trend over the seven years.

In regard to reoperation, a stable trend was observed between 2015 and 2021, representing 11.29% of the total 939 ophthalmic procedures in glaucoma patients in 2015 and 16.30% of the 1779 cases in 2021. Of these procedures,internal filtration surgery was the most common, accounting for almost over 50.00%, followed by bleb-management surgery. However, the proportions of external filtration and cyclodestruction surgeries were lower, at 12.30% and 7.70%of surgeries, respectively. There is no evident trend in the proportion change for these surgeries over the study period, as there are only minor fluctuations, as depicted in Table 5.

Figure 1 The trend of internal drainage surgery in different types of glaucoma A: The trend of internal drainage surgery in primary angleclosure glaucoma remined stable; B: The trend of internal drainage surgery in primary open angle glaucoma increased; C: The trend of internal drainage surgery in secondary glaucoma was upward; D: The internal drainage surgery in pediatric glaucoma presented the trend of escalation every year.

Table 2 The number of surgeries in different type of glaucoma in the Eye Hospital of Wenzhou Medical University from 2015 to 2021 n (%)

A distinct increase in internal filtration surgeries for glaucoma patients was identified over the seven year study period, which corroborates the findings of previous studies[20-21]. However,this study also found that the proportions of the different glaucoma surgeries had distinct features over this time.External filtration surgeries were the main surgical approach for POAG patients in 2015. Although Trab is traditionally the most popular and flexible surgical method, especially in combination with detachable suture technology, argon laser suture release technology, and viscoelastic materials, issues such as postoperative ocular hypotony, shallow anterior chamber,and bleb-related complications (infection, leakage, scarring),have been troublesome and unavoidable[19,21-22]. Subsequently,postoperative IOP reduction and visual quality have not been optimal in many Trab cases. Furthermore, Trab can accelerate lens degeneration, and the failure rate of Trab can be increased if cataract surgery is conducted subsequently[23]. Therefore,this explains the observed decline in Trab-related surgeries found in this study. In contrast, the number of internal filtration surgeries showed a considerable increase, accounting for more than half of the surgeries in 2021. Research has evidenced positive results in POAG patients following internal filtration surgery[24]. Meanwhile, a comparison of the safety, efficacy,and postoperative management of canaloplasty versus Trab with mitomycin C in POAG cases showed that both canaloplasty and Trab are effective in lowering IOP. However,canaloplasty was more favourable due to the fewer follow-up visits and significantly fewer complications and interventions compared with Trab[25]. Several other studies have shown similar results[26-27]. Moreover, this study found that more POAG patients were undergoing PCP; a previous long-termefficacy study identified the ability of PCP to sustain IOP reduction with a high complete success rate (81.3%) at 36 and 60mo postoperatively[28]. Compared with external filtration surgery, internal filtration surgery primarily aims to rebuild the function of the trabecular meshwork, and therefore, it is a more natural and physiological process to facilitate aqueous outflow.Internal filtration surgeries can be canal-based, whereby filtration is restored through Schlemm’s canal; this procedure is designed to retain the normal anatomy as opposed to removing it, and to be conjunctival bleb free, as this minimises the risk of long-term endophthalmitis and ocular hypotony[19]. Due to this advantage of being bleb-independent, internal filtration surgery has the potential to be the future dominating surgical method for POAG.

Table 3 The number of glaucoma surgeries in the Eye Hospital of Wenzhou Medical University from 2015 to 2021 n (%)

Table 4 Numbers and proportions of 3 types glaucoma surgery for various type of glaucoma in the Eye Hospital of Wenzhou Medical University from 2015 to 2021 n (%)

Table 5 Numbers and proportions of 4 types of glaucoma surgery for reoperation in the Eye Hospital of Wenzhou Medical University from 2015 to 2021 n (%)

The findings for paediatric glaucoma were similar to the trend of internal filtration surgery in POAG. The underlying mechanism of paediatric glaucoma involves maldevelopment of the trabecular meshwork and/or anterior chamber angle,resulting in reduced aqueous outflow, elevated IOP, enlarged corneal diameter, cupping of the optic disc, and a series of other clinical features[29]. Goniotomy or trabeculotomyab externoare often the preferred initial treatment for this disease[30]. In primary congenital glaucoma, Trab (with or without mitomycin-C) is typically reserved as a second procedure if angle surgery fails, or it is used as part of a combined approach with Trab. Children, especially infants,have a superior healing response compared with adults,meaning the risk of scarring of the fistula or the conjunctiva is higher; thus, the surgical outcomes of Trab for children are worse than for adults[31]. Nonetheless, as surgical technologies have undergone innovation in recent times, the development of 360° trabeculotomy has produced more accurate positioning of Schlemm’s canal and effective cutting of the trabecular meshwork. An extensive amount of literature has confirmed the superior results yielded by 360° trabeculotomy in terms of IOP control and success rates in paediatric glaucoma[30,32-33].Cyclodestructive procedures are considered a last resort option in refractory paediatric glaucoma, including cyclocryotherapy(the use of freezing temperatures), transscleral cyclophotoco-agulation (the use of laser), or endoscopic cyclophotocoagulation (the use of laser with endoscope). This is because cyclodestructive methods can damage the ciliary body and reduce the formation of aqueous humor. In most parts of the world, most paediatric glaucoma patients undergo internal filtration surgery to restore physiological aqueous drainage pathways. In 2015, there were only eight cases of childhood glaucoma in the Eye Hospital of Wenzhou Medical University hospital; however, the limited treatment experience at the time meant that half of these patients underwent Trab.As the hospital’s experience and number of patients in this situation have increased over time, more mainstream treatment methods have been implemented, especially internal filtration surgery.

PACG is more common in Asians than in Africans or Europeans[34]. This study showed that angle-closure glaucoma and secondary glaucoma were the most common types of glaucoma cases at the Eye Hospital of Wenzhou Medical University, which matched the findings of studies conducted in Shanghai[35], Tianjin[36], and Beijing[37]. In regard to angleclosure glaucoma, the proportion of internal filtration surgeries increased slightly from 2015 to 2021 to over 70% of patients.Of these patients, most underwent Phaco or Phaco-GSL.Patients with PACG have some specific anatomic abnormalities and are characterised by the thick lens and short axial length of their eyeballs, which can lead to pupillary block, narrowed anterior chamber, and subsequent increases in IOP[38-39].Phaco is an appropriate surgical treatment because it can deepen the anterior chamber and eliminate the pupillary block by removing the lens. According to the fifth edition of the European Glaucoma Guidelines, Phaco is chiefly recommended for primary angle closure and PACG patients who are aged 50 years and older[4]. A study reported the qualified success after Phaco-GSL as being over 85%, with the follow-up period over 12mo[40]. In the Eye Hospital of Wenzhou Medical University,Phaco-GSL was the most common antiglaucoma surgery prior to 2014[41]. However, internal filtration surgeries rebuilt access to Schlemm’s canal for aqueous humor. The present study also found that cataract extraction combined with an anti-glaucoma procedure was the second most common surgical treatment for angle-closure glaucoma. These findings could be due to several reasons; PACG with concurrent cataracts is fairly typical for aging glaucoma patients, and Phaco has become more widely accessible to patients due to the rapid economic developments and continued medical education programs in China[21]. This study identified a small number of patients who had received PCP, which had good efficacy and safety profiles,and maximally maintained the physiological anatomy of the operated eyes and restored the aqueous humor outflow in a bleb-independent manner, irrespective of the extent of angle closure[13].

Secondary glaucoma is a complex condition that is caused by a variety of factors. Based on the specific cause of glaucoma in each patient, an appropriate surgical procedure is selected.Previous studies have highlighted that GDI and Trab in secondary open-angle glaucoma and neovascular glaucoma patients, respectively, produced unsatisfactory results[42-43].In this study, PCP was performed for some of the patients with secondary glaucoma, such as traumatic angle recession glaucoma[14], steroid glaucoma[44], iridocorneal endothelial syndrome[45], satisfactory clinical outcomes were determined for these patients in terms of IOP control and avoidance of postoperative bleb-related complications. Therefore, internal filtration surgery for secondary glaucoma showed an increase in this hospital.

Whilst these are insightful findings, certain limitation must be acknowledged. The chosen surgical procedure is somewhat dependent on the experiences and preferences of the lead surgeon, thus, this sample had potential selection bias.

In conclusion, an increase in internal filtration surgeries based on physiological channels and non-bleb was identified in the surgical management of glaucoma in this study. The proportion of internal filtration surgeries accounted for over half of the total surgeries across a diverse range of types of glaucoma in the studied hospital. This anticipates internal filtration surgery as becoming the mainstream surgical procedure for glaucoma in the future. However, the trend does not mean the disappearance of external filtration surgeries, such as Trab or GDI, which are still the important surgical procedures for some type of glaucoma.

ACKNOWLEDGEMENTS

Authors’ contributions:Study concept and design: Liang YB,Cao Y, Lin HS; data collection, analysis and interpretation:Cao Y, Lin HS, Mao HY, Zhao Y; manuscript writing: Cao Y; statistical analysis: Cao Y, Lin HS; technical or material support, and supervision: Xie YQ, Zhang SD, Zhang Q,Wang PJ, Li GX, Fang AW, Liang YB; critical revision of the manuscript for intellectual content: Liang YB, Lin HS. All authors approved the final version of the manuscript.

Foundations:Supported by the National Key Research and Development Project of China (No.2020YFC2008200); the Program for Zhejiang Leading Talent of S&T Innovation(No.2021R52012); Key Research and Development Projects of Zhejiang Province (No.2022C03112); the Zhejiang Provincial Program for the Cultivation of Leading Talents in Colleges and Universities (No.2020099).

Conflicts of Interest: Cao Y,None;Lin HS,None;Mao HY,None;Zhao Y,None;Xie YQ,None;Zhang SD,None;Zhang Q,None;Wang PJ,None;Li GX,None;Fang AW,None;Liang YB,None.