Endoscopic cyclophotocoagulation for glaucoma compared to alternative procedures –A Systematic review

Abstract

INTRODUCTION:

Despite many recent developments, preference in the choice of surgical treatment of uncontrolled intraocular pressure (IOP) remains a challenge.

OBJECTIVE:

This study compares the clinical efficacy and safety of endoscopic cyclophotocoagulation (ECP) to alternative surgical procedures, for all types of glaucoma.

METHODOLOGY:

The methodology adheres to the preferred reporting items for systematic reviews and meta-analyses guidelines for systematic review reporting. Studies reporting ECP and alternative surgeries in treating refractory glaucoma, neovascular glaucoma, aphakic glaucoma, filtering surgical failure-induced glaucoma, congenital or juvenile glaucoma, and secondary glaucoma such as uveitis glaucoma, traumatic glaucoma, secondary glaucoma postcorneal transplantation, etc. were included. The efficacy was evaluated from the number of IOP-lowering drugs, and mean change in pre- and post-IOP were the outcomes assessed in ECP and non-ECP groups in this review. Evaluations of the postoperative complications revealed the safety assessment of the procedure.

RESULTS:

In total, 11 relevant studies were selected in this study with a total of 5418 eyes, including 763 eyes in the ECP group and 4655 in the non-ECP group. This review observed that both ECP and non-ECP procedures had been successful in reducing postoperative IOP.

CONCLUSION:

It can be deduced from this review, that all types of glaucoma can be treated efficiently with significantly higher success rates with ECP and ECP demonstrates lowest postoperative complications when compared to non ECP procedures. This review provides updated scientific evidence which caters to support clinical decisions for surgical treatment of glaucoma.

Introduction

Glaucoma is treated by cyclo-destructive procedures since 1930s by reducing the aqueous humor via the coagulation or destruction of the ciliary body.[1] In regard to the targeted ciliary destruction and the safety improvement, the surgical techniques for cyclodestruction have been very advanced recently.[2] Despite all the recent developments in this field, it remains a dispute and challenge in adopting the right surgical intervention to treat refractory glaucoma, such as neovascular glaucoma, aphakic or intraocular lens glaucoma, filtering surgery failure-induced glaucoma, congenital juvenile glaucoma, glaucoma complicated with uveitis, traumatic glaucoma, and glaucoma after vitrectomy.[2]

Cyclodestruction and filtering conventionally have been efficient in glaucoma treatment but had safety issues with postsurgical complications.[3] This is due to the inevitable injuries to the tissues surrounding the ciliary body during the procedure as it has to penetrate the sclera and destroy the ciliary body under a limited surgical field.[4,5]

Postoperative complications arise mostly from its the procedures failure to evaluate qualitatively the severity of the damage to the ciliary body.[5] Ablation of the ciliary processes with minor damage to the adjacent tissues can be carried out using a diode laser, either as Endoscopic Cyclophotocoagulation (ECP) or as Transcleral Cyclophotocoagulation (TCP)[6], Continuous Wave Transscleral Cyclophotocoagulation (CW-TSCPC), Micropulse Transscleral Cyclophotocoagulation (MP-TSCPC), and high-intensity focused ultrasound cyclodestruction are common variations of various cyclodestructive modalities.[7,8,9] Laser energy is utilized in ECP which is an endoscope-assisted technique to destroy the partial ciliary body and reduce the production of aqueous humor, thus lowering the intraocular pressure (IOP).[10]

ECP can be executed as a standalone procedure regardless of the status of the lens or combined with lens extraction.[11] Enhanced postoperative reduction of IOP has been reported with ECP for almost all types of glaucoma, including primary open-angle glaucoma, primary angle closure glaucoma, glaucoma secondary to neovascular or trauma, and congenital and normal tension glaucoma.[12,13,14,15] ECP has been gaining support and preference due to these reasons. A lower performance of ECP has also been advocated in some studies which stated lower efficacy of ECP in (pseudoexfoliative glaucoma, 30.4%) and uveitis and pediatric glaucoma.[16,17]

Many studies have been reported cyclophotocoagulation procedures, efficacies, and safety.[16,17,18,19,20,21,22] Studies evaluating by comparing ECP with similar and alternative procedures are very limited.[23,24,25] There has been no recent update and consensus on this topic to assist clinical decisions in surgical approaches to glaucoma. Updated scientific evidence is critical as there is debate regarding which cyclodestructive method is best and how they compare to other glaucoma surgeries. Thus, the objective of this review is to assess the relative effectiveness and safety of ECP compared with alternative surgical procedures in patients with refractory glaucoma of any type, within a time frame of 7 years from 2015 to 2022.

The participants, intervention, comparisons, and outcomes of the current systematic review were as follows: Participants (P): Patients who underwent surgical intervention for glaucoma; Intervention (I): ECP for surgical treatment of glaucoma; Comparisons (C): Alternative surgical procedure for treating glaucoma; and Outcomes (O): Efficacy of treatment from the evaluation of the postoperative mean IOP reduction and the mean reduction in IOP lowering medications along with postoperative complications assessment, and safety of treatment from the assessment of success rates of the treatment. Hence, this review raises the question does ECP present better clinical efficacy and safety for the surgical treatment of glaucoma as compared to alternative surgical procedures for treating glaucoma?

Methodology

This systematic review complies with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA)[26] statement. The institutional research board and ethics committee ruled out that approval was not required for this study being a review study. This study has been registered in Prospero[27] with ID: CRD42022326806.

Publication search strategy

Studies reporting cyclodesctructive procedures, ECP, and glaucoma surgeries were retrieved from medical bibliographic databases. Cochrane Central Register of Controlled Trials (which contains the Cochrane Eyes and Vision Trials Register) Ovid MEDLINE, Embase.com, PubMed, and ClinicalTrials.gov were searched for relevant papers published from January 2015 to February 2022. Search terms included “ECP,” “cyclophotocoagulation,” and “glaucoma surgeries,” “cyclodestructive procedures” in. AND, NOT, OR Boolean operators were used between the keywords to guarantee the systematic searching. Table 1 shows the design of the keywords used in this study.

Table 1.

Keywords used in the database search

Database	Keyword strategy
PubMed,	1. Endoscopic cyclophotocoagulation
Web of science,	AND
Cochrane and others	Glaucoma surgeries
	OR
	Cyclophotocoagulation
	2. Refractive glaucoma
	AND cyclodestructive procedures
	OR endoscopic cyclophotocoagulation
	NOT
	3. Non-English,
	4. Animal subjects

Inclusion and exclusion criteria

The inclusion and exclusion criteria were designed for this systematic review were designed to assess the most recent articles describing the topic of review with respect to the participants, intervention under study, comparison of the intervention under study with similar treatments and the postoperative outcomes of the treatment studies. Table 2 is descriptive of the designed inclusion and exclusion criteria.

Table 2.

The inclusion and exclusion criterias for the study selection

	Inclusion criteria	Exclusion criteria
Participants	All types of participants (adults and pediatric) diagnosed with any type of refractive glaucoma.	Animal studies
Intervention	Studies with Endoscopic cyclophotocoagualtion for glaucoma treatment with any laser type, route of administration, and laser settings	Non glaucoma studies Descriptive studies without demographic data and therapeutic measures of the subjects
Comparison	Studies comparing Endoscopic cyclophotocoagualtion with alternative surgical intervention glaucoma treatment.	Studies with patients in the control group did not undergo surgery, insufficient raw data
Outcomes	Studies which observed and stated efficacy of treatment with post-operative mean IOP reduction and mean reduction in intraocular pressure lowering medications, and the success rates to assess the safety of treatment.	Studies that have not adequately defined post-operative outcomes of the treatment,
Study designs	All methodologies of clinical trials, systematic reviews, meta-analysis, and case series	Conference proceedings, letter to editors, narrative reviews
Language	English publications	Non English publication without English translations available.
Availability	Full texts available	Abstracts only available, Author duplicate publications
Time	From 2015 till 2022	Dated before 2015

Data extraction and synthesis

The selected titles and abstracts were reviewed, and full-text reports were retrieved of those that were potentially relevant, and later classified as included or excluded. Data from the included studies were extracted into a predesigned spreadsheet. These data included the publication details, methodological attributes, and postoperative outcomes featured in the study, laser technique used, participant’s number, and demographics. Tables 3-5 are illustrative of this data extraction and synthesis.

Table 3.

The summary of the attributes included studies

Study	Study type	Study population	Follow up	Country	Non ECP type compared	Remarks
Lanzagorta[30]2021	Retrospective, non-randomized cohort	Refractory glaucoma patients	1 year	Spain	Transcleral yclophoto coagulation	Despite the post-operative complications of TCP, both TCP and ECP are effective at decreasing intraocular pressure.
Bakr[31] 2021	Retrospective case–control	Cataract and glaucoma patients	4 years	KSA	Trabeculectomy with MMC	ECP is safe and effective as a primary procedure alternative to combined cataract and trabeculectomy surgery for glaucoma patients having cataract.
Koduri[32]2021	analysis	Refractory glaucoma patients	1 year	USA	Phacoemulsification only	The addition of endoscopic cyclophotocoagulation to phacoemulsification significantly increases the risk of developing PAU in the post-operative period compared to phacoemulsification alone.
Klug[33]2022	Retrospective Comparative case series	Refractory glaucoma patients	1 year	USA	Dual blade ab interno trabeculectomy (PEcK)	Both PEcK and ECP provide clinically relevant reductions in IOP and glaucoma medication burden.
Bartolomé[34]2018	Retrospective notes review	POAG patients	1 year	UK	Combined phacoemulsification	Phaco-ECP is both safe and effective as surgical management for cataract and glaucoma.
Feinstein[35] 2019	Retrospective study	Refractory glaucoma patients	2 years	USA	Pars plana (ECP-plus)	ECP-plus may offer superior IOP control for the management of glaucoma
Marco[36]2017	Retrospective cohort study	POAG patients	6 months	Canada	Trabeculectomy with mitomycin C (trab) with cataract surgery	ECPphaco patients had higher incidences of immediate postoperative complications.
Kang[37]2017	Retrospective case series review	POAG patients	21 months	UK	Combined with phacoemulsification	Phaco-ECP can be considered as an effective, safe and predictable surgical treatment option for glaucoma patients with co-existing cataract
Beardsley[38] 2017	Retrospective chart review	Refractory glaucoma patients	1 year	USA	Transcleral cyclophotocoagulation	TCP was associated with a higher rate of post-operative complications.
Murakami[39]2017	Retrospective, nonrandomized, interventional case series	Refractory glaucoma patients following a failed initial tube shunt	2 years	USA	Implantation of a second GDD-2	Both ECP and GDD-2 are both effective as second surgeries for refractory glaucoma that has failed a prior aqueous shunt.
Siegel[40] 2015	Retrospective chart review	Refractory glaucoma patients	36 months	USA	Combined phacoemulsification	Phaco-ECP may help to increase medication compliance and reduce glaucoma progression in mild to moderate glaucoma.

ECP: Endoscopic cyclophotocoagulation, TCP: Transcleral cyclophotocoagulation, PEcK: Dual blade ab interno trabeculectomy, GDD: Glaucoma drainage device, IOP: Intraocular pressure, PAU: Persistent anterior uveitis, POAG: Primary openangle glaucoma, MMC: Mitomycin C (MMC)

Table 5.

ECP and non ECP comparisons of post-operative mean IOP reduction and mean reduction in intraocular pressure lowering medications and complications

Study	Mean post-operative Medicines reduction		Mean post-operative IOP (mmHg) reduction		Post-operative Complications
					% phthisis bulbi		% Pupil irregularity		% Hypotony		% Cystoid macular edema, CME
	ECP	Non ECP	ECP	Non ECP	ECP	Non ECP	ECP	Non ECP	ECP	Non ECP	ECP	Non ECP
Lanzagorta[30] 2021	3.6±0.4	3.5±0.5	24.4±6.2	21.1±4.1	0.0	5.0	3.0	8.0	0.0	2.0	13.0	24.0
Bakr[31] 2021	2.00±0.9	1.50±1.1	12.88±3.48	15.24±7.04	0.0	5.9	0.0	5.9	NA	NA	0.0	0.0
Koduri[32] 2021	NA	NA	13.3±3.7	14.2±3.2	3.7	25.0	14.9	1.7	0.0	0.0	3.7	25.0
Klug[33] 2022	0.94±0.94	1.7±1.2	13.3±2.8	14.1±3.4	0.0	6.0	0.0	4.0	0.0	0.0	0.0	0.0
Bartolomé[34] 2018	0.73±0.71	0.23±0.56	4.5±5.13	1.83±3.61	NA	NA	0.0	1.5	0.0	5.8	NA	NA
Feinstein[35] 2019	−1.11 0.36	−0.13 0.36	16.4±5.5	12.1±5.6	0.0	0.0	1.0	0.0	1.0	1.0	NA	NA
Marco[36] 2017	1.39±1.09	0.48±0.92	14.2±3.6	13.0±2.5	0.0	2.0	0.0	1.0	0.0	5.0	NA	NA
Kang[37]2017	2.3±3.1	2±3	−7.7±47.8	22.6±47.8	4.8	20.5	2.0	0.0	2.0	4.0	2.0	2.0
Beardsley[38] 2017	1.9±1.3	0.3±0.46	14.4±3.95	4.9±2.11	0.0	1.0	1.6	6.5	0.0	0.0	0.0	0.0
Murakami[39]2017	1 1.5±1.9	1 0.9±1.6	18.1±7.4	14.6±3.8	0.0	0.0	0.0	0.0	0.0	1.0	0.0	0.0
Siegel[40] 2015	0.2±0.6	1.3±0.6	14.7±3.1	15.5±3.6	0.0	0.0	0.0	1.0	0.0	1.0	0.0	1.0
Final	1.06±0.8	1.06±0.7	11.04±1.5	13.7±2.9
	P value P=0.01		P value P=0.4

Quality of studies and assessment of the risk of bias

The risk of bias method from the Cochrane Collaboration was used[28] to appraise the quality of the included studies. The studies were graded as low, high, or unclear risk of bias for each of the following items using this method. The domains included in this grading of risk of bias were the random sequence generation and allocation concealment, (both items relate to selection bias), masking of participants and personnel (detection bias), incomplete outcome data (attrition bias), selective reporting (reporting bias), and other biases. Figure 1 is descriptive of the risk of bias summary used in this study.

Figure 1.

PRISMA flow chart descriptive of the study selection[29]

Results and Discussion

Study search

The PRISMA flow diagram of the study selection procedure is shown in Figure 2. A total of 1191 studies from 2015 to 2022 were originally identified and articles were filtered according to the predesigned inclusion and exclusion criteria. Only 11 studies with a total of 5418 eyes, including 763 eyes in the ECP group and 4655 in the non-ECP group were included in the subsequent review, illustrated in Figure 1, and Table 3 provides the summary of the attributes included studies.

Figure 2.

Risk of bias summary about the methodological quality of studies included using the Cochrane risk of bias tool. Symbols show low risk of bias (+), unclear risk of bias (?) or high risk of bias (-)

Characteristics and quality of trials

In relation to the randomizing of the trials, all the studies were at “high risk of bias”: due to being nonrandomized and this is a clear indication of a research gap in this field of intervention for glaucoma treatment. All the included studies did not have performance bias they were all were doubled blinded studies. There was no reporting bias in any studies included as they were all at “low risk of bias.” As for attrition bias, most trials were rated at “low risk of bias,” because they reported the complete outcome data (10 out of 11 trials, 90.10%). %). Figure 2 is illustrative of the risk of bias summary based on review quality appraisal judgements about each risk of bias item for each included study included using the Cochrane risk of bias tool.[29] Symbols show a low risk of bias shown as “+,” unclear risk of bias shown as “?” or high risk of bias shown as “−.” Figure 3 shows the risk of bias graph with judgments about each risk of bias item presented as percentages across all included studies.

Figure 3.

Risk of bias graph with judgements about each risk of bias item presented as percentages across all included studies

Clinical outcomes

This review was grouped into ECP versus non-ECP for outcome comparisons. The efficacy of the procedure was assessed from the postoperative mean reduction in IOP and postoperative mean reduction in IOP-lowering medications. The postoperative complications were observed to review the safety evaluation ECP and non-ECP procedures. The success rate comparison between the procedures gave the long-term benefit picture of the procedures under comparison.

Success rates

Ten of the included studies[30,31,33,34,35,36,37,38,39] reported the success rate of ECP and non-ECP in treating refractory glaucoma. These values were reported based on the longest follow-up period. From the mean of the values representing 5350 eyes, the significant lead of ECP surgical procedures for treating glaucoma is very apparent from the mean success rate of 73.53% for ECP in comparison with non-ECP with 46.34%. These observations along with the laser setting used for the procedures are illustrated in Table 4.

Table 4.

Success rates and laser settings for ECP and Non ECP procedures

Study	No of Eyes			Success Rates %		Laser Settings
	ECP	Non ECP	Total	ECP	Non ECP	ECP	Non ECP
Lanzagorta[30]2021	30	32	62	93.8	83.3	Endo Optiks Inc., Little Silver, NJ, USA)	G-Probe; IRIS Medical Instruments, Inc., Mountain View, CA, USA)
Bakr[31] 2021	181	4242	4423	64.7	29.4	NA	NA
Klug[33] 2022	23	53	76	44	51	NA	NA
Bartolomé[34]2018	69	30	99	69.6	40	Iridex OcuLight SL or Iridex IQ	Iridex OcuLight SL or Iridex IQ
Feinstein[35] 2019	54	25	79	80	33.3	NA	NA
Marco[36] 2017	34	33	67	75	31	NA	NA
Kang[37]2017	62	62	124	100	90	Infinity Vision System; Alcon Laboratories, Fort Worth, TX, USA	20G ECP probe (E2; Endo Optiks, Little Silver, NJ, USA)
Beardsley[38]2017	42	44	86	63.6	30	EndoOptiks E2 system 810 nm diode laser (Endo Optiks, Inc., Little Silver, NJ, USA)	IRIS Oculight 810 nm with G-Probe (Iridex, Inc., Mountain View, CA, USA).
Murakami[39] 2017	25	48	73	72	52.1	Endo Optiks, Little Silver, NJ, USA	Abott Medical Optics, Santa Ana, CA, USA)
Siegel[40] 2015	209	52	261	72.6	23.3	Endo Optiks, Little Silver, NJ, USA	Endo Optiks, Little Silver, NJ, USA

ECP: Endoscopic Cyclophotocoagulation; TCP: Transcleral Cyclophotocoagulation; CME: Cystoid Macular Edema; PEcK: Dual Blade Ab Interno Trabeculectomy; GDD: Glaucoma Drainage Device; IOP: Intra Ocular Pressure; PAU: Persistent Anterior Uveitis; POAG: Primary Open-Angle Glaucoma

Postoperative mean intraocular pressure reduction and mean reduction in intraocular pressure lowering medications

All of the included studies[30,31,32,33,34,35,36,37,38,39] reported the mean postoperative reduction IOP and with standard deviation after ECP and non-ECP in treating refractory glaucoma. Table 5 is descriptive of the postoperative mean IOP reduction and the mean reduction in IOP lowering medications comparisons between the two groups. Though there is no significant difference (P = 0.001) in the mean IOP lowering medicines in both ECP and non-ECP procedures, it can be seen ECP had a significant reduction in postoperative IOP reduction in comparison with non-ECP procedures (P = 0.4).

Postoperative complications

Most of the studies reported post-operative complications like Cystoid macular edema, CME, hypotony, pupil irregularities and phthisis bulbi. Table 5 summarizes the post-operative complication comparisons between the ECP and non ECP groups. The mean values of each observed variables as seen from the table 5 clearly reinstates the minimal post-operative complications observed with ECP procedures as compared to non ECP methods.

Conclusion

Adopting the right surgical technique in treating different types of refractory glaucoma, is still a debate and a challenge. Other treatment options like filtering surgery combined with antimetabolites are the currently adopted modality;[40] aqueous shunt implantation including Molteno and Baerceldt drainage shunt without a valve and Krupin, Ahmed, and OptiMed valve implantation.[41,42] suprachoroidal drainage (filtering surgery),[43] scleral diathermy, cyclocryotherapy, and cyclophotocoagulation are the types of cyclodestruction procedures where scleral diathermy and cyclocryotherapy tend to result in postoperative atrophy of eyeball due to severe pain during and after surgery, and thus are rarely applied in clinical practice.[44,45,46,47] Thus, this review highlights the importance of reviewing the widely practiced methods for surgically treating glaucoma to provide an evidence-based guidance in clinical decision-making. This review results asserts ECP is a reliable method of treating different types of refractory glaucoma.

Implications for practice

Evidence assimilated in this review clearly points out that, ECP can be presumed as a successful, safe, and efficient surgical treatment of all types of refractory glaucoma. From the postoperative complications evaluations, the complications faced by non-ECP methods are many and presents with the need of greater amount of postoperative IOP lowering medicines and the requirement for re-surgeries, which presents a hurdle to its long-term success rates. ECP which is seen to be superior in these aspects thus can be visualized as a long-term visual function-promoting procedure for glaucoma patients. There are vast differences in the methodologies of the included studies in this review, and thus the evidence from the included studies can be stated only as a support in clinical judgment and not a conclusive statement to advise clinical recommendations regarding the use of ECP and other cyclodestructive procedures.

Limitations

This systematic review has some limitations that should be acknowledged. A serious setback in this review is the explicit lack of randomized controlled trials (RCT) which can be inferred from the included studies. Due to the variety in the included methodologies and the lack of RCTs, a meta-analysis was not done in this review. Meta-analysis was also not feasible as heterogeneity might arise between the ECP and non-ECP groups when multiple surgical methods were adopted in the non-ECP group, which can affect the analysis outcomes and its reporting. The data reported by the studies were inconsistent between observational and analytical studies especially in reporting the postoperative complications.

This review emphasizes a clear lack of studies on evaluating the quality of life (QOL), and cost-benefit ratio for patients undergoing glaucoma surgical procedures. Typically, the cost of the machines is considered to be a significant factor restricting the development of a surgical technique. Some studies[30,31,33,36] are not explicit about the laser equipment used but refer to the surgical process only. Expect just one study[28] which was set in KSA, all the other studies are set in the US and European countries, this could deflect the outcome analysis based on ethnic factors. None of the included studies did not observe and report pain score and patient satisfaction levels, so it could not be brought for comparison in this review. The IOP-lowering degree, safety, and incidence of complications remain to be further elucidated by RCTs with a larger sample size.

Implications for research

To supplement and update clinical guidelines of surgical practices in glaucoma, prospective and retrospective controlled trials should be undertaken comparing ECP with other glaucoma surgeries. Future research should address and differentiae clearly the efficacy of the procedures on the clinical outcomes among participants with prior surgical intervention experiences and those who have not. Refractory glaucoma being a debilitating and advanced disease, patient-reported outcomes like QOL, pain scores should be assessed and evaluated in future trials as primary outcomes. Industrial funding is an area in research which is usually overlooked. External funding agencies influence and impact the favoring of certain commercial equipment, which again deforms the true effect of a method under study.

Patient and public involvement

This study being a systematic literature review, the patients selected were recruited by the researchers of the included studies. All the patient and families related aspects involved in the design and implementation of the interventions were priori addressed by the authors of the selected studies.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest