Comparison between MIGS with trabeculectomy in the management of open-angle glaucoma with cataract: A systematic review

Abstract

Age is an important risk factor for both glaucoma and cataract. As global life expectancy continues to rise, the prevalence of concomitant open-angle glaucoma (OAG) and cataracts is increasing. Currently, there is a lack of definitive consensus on the optimal management approach for such individuals. Conventionally, trabeculectomy (Trab) in combination with phacoemulsification is the preferred method. Recent developments in microinvasive glaucoma surgery (MIGS), which offer similar results with fewer complications, provide a new possible approach to this condition. This study aimed to assess the current knowledge of combination surgery in patients with cataract and OAG to provide a comprehensive understanding and help its implementation in clinical settings. A comprehensive systematic search was conducted in May 2021 on five databases (MEDLINE, Embase, SCOPUS, Proquest, EBSCO, and Cochrane Library). The results were filtered for English and human studies but not publication year. All studies published up to May 2021 were reviewed. Newcastle–Ottawa Scale and PEDro scale were used to screen studies for risk of bias where appropriate. Four studies satisfied the inclusion criteria and were subsequently added in this review. Study designs consisted of one RCT and three descriptive studies. Appropriate assessment tools were used; these studies demonstrated moderate to good quality. Postoperative mean IOP, IOP reduction, and qualified success rates were comparable in the Phaco-MIGS (Phaco-endoscopic cyclophotocoagulation (ECP), Phaco-ab interno trabeculectomy (AIT)) and Phaco-Trab group. Severe complication was reported only in the latter. Phaco-MIGS (in particular, trabectome) shows excellent promise as an option for individuals with OAG and concomitant cataract; further research through RCT is required to validate these findings.

Glaucoma is a group of disorders with progressive multifactorial optic neuropathy represented by loss of neuronal tissue, excavation of the optic disc, and thinning of the nerve fiber layer.[1] It is the leading cause of irreversible vision loss in the world. According to the Vision Loss Expert Group of the Global Burden of Disease Study published by The Lancet, in older populations, cataracts and glaucoma were the two leading causes of blindness globally.[2,3,4] Around 76 million individuals aged 40–80 years suffered from glaucoma in 2020, with a predicted constant increment in prevalence to reach 112 million individuals by 2040, affecting more people in Asia and Africa.[2,3] The main risk factor for the development and progression of the disease is intraocular pressure (IOP). Thus, the mainstay treatment of glaucoma is to reduce IOP through drugs or surgical intervention.[1] Primary open-angle glaucoma (POAG) is the most common subtype of glaucoma.[3,5] The prevalence of POAG is closely related to age, with an increased odds ratio prevalence of 1.73 for each decade increase in age.[3] Cataracts, the leading cause of blindness globally, also contribute largely to the prevalence of age-related eye diseases. With increasing life expectancy, their coexistence is becoming more common in the elderly population.[6,7,8] As aging is one of the most influencing risk factors in eye disease, the aging population will directly increase the number of people with cataracts and glaucoma.[4,9]

There is currently no clear consensus on the management of these concomitant diseases. From a surgical standpoint, cataract surgery may enhance aqueous drainage; however, patients are more likely to require medication postoperatively.[7,8,9] In addition, for patients with OAG, this might be insufficient to reach the IOP goal; thus, conventionally, phacoemulsification with trabeculectomy is the approach taken.[10,11]

Trabeculectomy is the gold standard of glaucoma surgical management. However, despite its effectiveness and success in reducing IOP, trabeculectomy is associated with prolonged recovery time and postoperative complications such as choroidal effusion, hyphema, bleb leak, and ptosis.[12]

Microinvasive glaucoma surgery (MIGS) is a novel surgical method mainly used to treat mild and moderate glaucoma by lowering the IOP with as minimum trauma as possible while avoiding the postoperative complications encountered in conventional glaucoma filtration surgery.[13] MIGS constitute several groups of surgical approaches that share common characteristics: high safety profile, enhanced aqueous outflow mechanism without major alteration of ocular anatomy, an ab interno approach, comparable efficacy to traditional filtering surgery, and rapid recovery with the least additional downtime.[13,14]

The approaches in the MIGS procedure reduce IOP through one or several of the following four mechanisms: (1) enhancing trabecular outflow, (2) ablation of the ciliary body to decrease aqueous production, (3) increased alternate pathway outflow, and (4) subconjunctival filtration.[14]

The trabecular meshwork offers the greatest resistance to aqueous outflow. MIGS procedure that aims to enhance trabecular outflow may do so by stenting (i.e., iStent, Hydrus) to circumvent the aqueous flow to allow direct drainage from the anterior chamber into Schlemm’s canal, trabecular meshwork tissue excision (i.e., Trabectome), or widening of the Schlemm’s canal. Other MIGS work to enhance aqueous outflow through the uveoscleral pathway (i.e., CyPass microstent) or into the subconjunctival space (i.e., XEN glaucoma implants). Lastly, another target for MIGS procedures to reach the IOP goal is reducing aqueous production through ciliary body ablation by using a laser unit (i.e., endocyclophotocoagulation). Compared to trabeculectomy, MIGS in conjunction with phacoemulsification may provide the same benefit with fewer complications in individuals with mild-to-moderate glaucoma and a population that does not meet the criteria of trabeculectomy.[13,14,15,16]

This study aimed to assess the current knowledge of combination surgery in patients with cataract and OAG to provide a comprehensive understanding and guidance in clinical practice.

Methods

This systematic review was written according to the Guidelines for Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) guidelines 2020. No protocol was prepared prior to the writing of this review.

Search strategy

To discover the appropriate direction for practice and treatment in POAG and cataracts, a comprehensive systematic search was done on May 5, 2021, comprising Boolean operators (AND, OR, NOT), wildcards, and truncation. The keywords used in the search process include microinvasive glaucoma surgery, trabeculectomy, glaucoma, iStent, Hydrus, Xen, Trabectome, endocyclophotocoagulation, micropulse, Omni, Cypass, cataract, and phacoemulsification. Additional filters were applied for English language studies and human studies. The systematic literature search was conducted on these databases: Medline Library, Embase, and SCOPUS-Elsevier. Grey literature was also included and searched for using Proquest and EBSCO. A manual search for additional studies was also conducted through relevant publications.

Eligibility criteria

Inclusion criteria were formulated using the Population, Intervention, Comparison, and Outcome (PICO) formula. The following criteria were used: adult population (>18 years old) with OAG and concomitant cataract in either eye undergoing a combination surgery of either phacoemulsification and trabeculectomy or phacoemulsification and MIGS, cohort, case series, case-control or randomized controlled trial study design, English as a primary language, without publication year limitation. Exclusion criteria were animal studies, case reports, conference proceedings, and review papers.

Data collection

Search results were documented and managed using Endnote (X9.3.3), where duplicate studies were screened and removed. Title and abstract screening of each unique article was conducted by two independent reviewers (AZ and TGP) against the established inclusion and exclusion criteria by using Covidence. Full-text reviews were then performed on the identified articles. Studies were extracted by including publication year, study design, number of participants, intervention received, length of follow-up, and success cutoff for IOP reduction. Only study participants receiving combinations of either phacoemulsification and trabeculectomy (Phaco-Trab) or phacoemulsification and MIGS (Phaco-MIGS) were reviewed and analyzed. Any disagreements were resolved through discussions among reviewers with the senior authors until a consensus was reached.

Critical appraisal

Included studies were examined for risk of bias by using appraisal tools. Newcastle–Ottawa scale was employed for case series, case-control, and cohort studies, whereas the PEDro scale was employed to determine the risk of bias in RCT studies.[17,18] Two independent reviewers (AZ and TGP) analyzed the studies by following the tool criteria.

Results

Search finding

Using the aforementioned search criteria, 1454 articles were established at first. After eliminating 598 duplicates, a total of 856 studies remained. Those studies were then filtered based on the title and abstract, and a further 796 studies were excluded because they were non-OAG study populations, review papers, case report studies, guidelines, child populations, animal studies, or irrelevant topics. The remaining 60 studies were then analyzed for full-text assessment. Subsequently, 56 studies were removed due to the following reasons: 36 studies were removed due to not having phacoemulsification and trabeculectomy combination surgery as a comparator, 19 studies were removed due to study participants not diagnosed with either cataract or OAG, and one study was removed for not having a subanalysis for the key outcome on the OAG population in the study [Fig. 1].

Figure 1.

PRISMA flow diagram of study selection

Quality assessment of included studies

Quality assessments of the four included studies were done using appropriate tools in concordance with their study design. Newcastle–Ottawa scale (NOS), as seen in Table 1, was used to assess the risk of bias of three cohorts included in this review. The scale comprised eight questions regarding the selection of study groups, comparability, and confirmation of outcomes. In total, if all eight questions are satisfied, a maximum of nine stars could be rewarded. The cohort studies included in this systematic review were awarded 6–9 stars, indicating a moderate to excellent quality of studies.[19,20,21,22]

Table 1.

Newcastle–Ottawa quality assessment

Study		Newcastle–Ottawa Quality Assessment																Critical appraisal rating
		Selection								Comparability		Outcome/Exposure
Lau et al., 2018[22]				*		*		*		*		*		*		*		7
Parra et al., 2019[20]		*		*		*		*		**		*		*		*		9
Töteberg-Harms et al., 2017[21]						*		*		*		*		*		*		6

PED ro scale, as shown in Table 2, was employed to assess one randomized controlled trial study by Ting et al. (2018).[19] The study was a single-blind randomized controlled trial in which only the participants were blinded to their group allocation. The therapists who administered the intervention and the assessor who measured the outcome were not, hence a possible source of bias. The study satisfied other scale criteria and exhibited good reliability.

Table 2.

PEDro scale

Ting et al., 2018[19]
Eligibility criteria were specified		Yes		Individuals aged 40–85 years old, with OAG (≥ Shaffer grade 2), inadequately controlled glaucoma and/or IOP on medical therapy; visually significant cataract with BCVA ≤20/30
Subjects were randomly allocated to groups (in a crossover study, subjects were randomly allocated an order in which treatments were received)		Yes		Block randomization was performed
Allocation was concealed		Yes		Randomization was done by the study coordinator to blind participants
The groups were similar at baseline regarding the most important prognostic indicators.		Yes		Baseline IOP in both groups are not statistically significant (Phaco-AIT (Ab interno trabeculectomy or Trabectome) vs. Phaco-Trab, 20 vs. 23.1, P=0.22)
There was blinding of all subjects.		Yes		There was blinding of study participants
There was blinding of all therapists who administered the therapy		No
There was blinding of all assessors who measured at least one key outcome		No
Measures of at least one key outcome were obtained from more than 85% of the subjects initially allocated to groups.		Yes		Measurements were obtained on all subjects
All subjects for whom outcome measures were available received the treatment or control condition as allocated; where this was not the case, data for at least one key outcome was analyzed by intention to treat		Yes		All subjects received treatment according to the group allocated
The results of between-group statistical comparisons are reported for at least one key outcome		Yes		Statistical comparisons are reported on key outcomes
The study provides both point measures and measures of variability for at least one key outcome		Yes
Total				9/11

Data extraction

Study characteristic

The characteristic summary of the included studies is presented in Table 3, with a total of 306 OAG eyes from 276 individuals. Of this, only 140 and 119 eyes received a combination of phacoemulsification and trabeculectomy (Phaco-Trab) or MIGS (Phaco-MIGS), respectively. Thus, a total of 259 eyes were analyzed in this study. The included studies’ most common OAG diagnoses were POAG and pseudoexfoliative glaucoma (PEG). One retrospective cohort study (Parra et al.), one case-control study (Lau et al.), one case series study (Töteberg-Harms et al.), and one randomized controlled trial (Ting et al.) were included, all published between 2017 and 2019. All studies performed phacoemulsification combined with trabeculectomy (Phaco-Trab) or phacoemulsification and MIGS (Phaco-MIGS). The MIGS procedure discussed in this review included endocyclophotocoagulation, ab interno trabeculectomy, Xen gel implant, and Excimer laser trabeculostomy.[19,20,21,22]

Table 3.

Characteristics of included studies

Study		Population		Intervention		IOP definition of qualified success		Follow up period		Risk-of-bias scoring
Randomized controlled trial										PEDro scale (/11)
Ting et al.[19]		19 eyes from 19 patients with open-angle glaucoma (Shaffer grade ≥2)		Ab interno trabeculectomy (Trabectome) trabeculectomy with mitomycin C combined with phacoemulsification		≤21 mmHg or ≥20% reduction from baseline IOP		1, 3, 6, and 12 months		9
Descriptive studies										Newcastle–Ottawa scale (/9)
Lau et al.[22]		53 eyes of 53 patients with open-angle glaucoma		Phaco-ECP (Endoscopic Cyclophotocoagulation) vs. Phaco-trab		≤15 mmHg or ≥30% reduction from baseline		6 months		7
Parra et al.[20]		74 eyes with open-angle glaucoma		Phaco-Xen (XEN Implant) vs. Phaco-trab		IOP ≥6 and ≤16 mmHg		1 day, 1 week (±2 days), 1 month (±1 week), 3 months (±2 weeks), 6 months (±2 weeks), 12 months (±1 month)		9
Töteberg-Harms et al.[21]		113 eyes from 113 patients with open-angle glaucoma (Shaffer 3 or 4)		Phaco-ELT (Excimer laser trabeculotomy) vs. Phaco-Trab		≤21 mmHg or ≥20% IOP reduction from baseline		1 year, 4 years		6

In our review, follow-up ranged from 1 day to 4 years post procedure. Lau et al. conducted a single follow-up assessment at 6 months post surgery, In contrast, Parra et al. did the most extensive follow-up assessment at 1 day, 1 week, and 1, 3, 6, and 12 months post intervention.[20,22] The longest follow-up period was by Töteberg-Harms et al., in which the patients were followed up to 4 years post procedure.[21]

Success criteria for IOP reduction differed between the studies included. Ting et al. and Töteberg-Harms et al. defined successful IOP reduction as IOP ≤21 mmHg or a drop of at least 20% from baseline.[19,21] Lau et al. used a cutoff of ≤15 mmHg or ≥30% reduction from baseline, while Parra et al. defined success as IOP ≤16 mmHg postoperative without antiglaucomatous medication.[20,22]

Baseline IOP measurement

Prior to treatment, IOP was measured in all studies to ascertain the difference in baseline IOP, as shown in Table 4. Three studies used Goldmann applanation tonometry to measure IOP (Ting et al., Lau et al., and Töteberg-Harms et al.).[19,21,22] Ting et al., in particular, recorded IOP measurements from the mean of two consecutive measurements.[19] No description was given by Parra et al. on the method used for measuring IOP.[20] Baseline IOP in the MIGS group showed a lower trend in comparison to the trabeculectomy group, and this difference was statistically significant (P < 0.05) except in the study by Ting et al. (20 mmHg vs. 23.1 mmHg, P = 0.22).[19,20,21]

Table 4.

IOP at baseline

Study		Method of measurement		Baseline IOP (mmHg)				P
				Phaco-MIGS		Phaco-Trab
Ting et al.[19]		Goldmann applanation tonometry, recorded as the mean of two consecutive measurements.		20		23.1		0.22
Lau et al.*[22]		Goldmann applanation tonometry.		18		20.5		0.003
Parra et al.[20]		-		18.0±4.5		20.0±4.7		0.0765
Töteberg-Harms et al.[21]		Goldmann applanation tonometry		19.0		22.8		<0.001

*IOPs are expressed in median

Mean IOP during follow-up

Only two studies reported IOP points during follow-up. Ting et al. reported no significant difference in mean IOP between the Phaco-AIT group and the Phaco-Trab group at 6 months (17.5 mmHg vs. 16.0 mmHg, P = 0.54) and 12 months follow-up (16.8 mmHg vs. 17.1 mmHg, P = 0.57).[19] Interestingly, in a study by Töteberg-Harms et al., the Phaco-Trab group showed higher IOP at baseline in comparison to the Phaco-ELT group (22.8 mmHg vs. 19.0 mmHg, P < 0.001), whereas at 1-year follow-up, the Phaco-Trab group showed lower median IOP (13.0 mmHg vs. 15.0 mmHg, P < 0.001). However, these differences diminished at 4 years follow-up, where both groups had a median IOP of 14.0 mmHg (P = 0.097)[21] [Table 5].

Table 5.

Mean IOP

Author		Time of follow-up		IOP (mmHg)				P
				Phaco-MIGS		Phaco-Trab
Phaco-AIT vs. Phaco-Trab
Ting et al.[19]		6 months		17.5±3.8		16.0±6.0		0.54
		12 months		16.8±2.7		17.1±5.0		0.57
Phaco-ELT vs. Phaco-Trab
Töteberg-Harms et al.*[21]		1 year		15.0		13.0		<0.001
		4 years		14.0		14.0		0.097

*Data presented as median

IOP change

Four studies reported IOP evolution between the Phaco-MIGS and Phaco-Trab groups throughout their follow-up periods. Neither group had a statistically significant difference in each follow-up visit performed by Lau et al. and Ting et al.[19,22] Studies by Parra et al. and Töteberg-Harms et al. found a statistically significant difference in mean IOP reduction between the Phaco-MIGS and Phaco-trab groups at postoperative follow-up visits.[20,21] However, no significant difference in mean IOP changes was reported after 6 months (−4.3 mmHg vs. −7.1 mmHg, P = 0.36) in a study by Parra et al.[20] All studies reported statistically significant IOP reduction postoperative compared to baseline (P < 0.05)[19,20,21,22] [Table 6].

Table 6.

IOP reduction during follow-up

Study		Time of follow-up		IOP (mmHg)				P
				Phaco-MIGS		Phaco-Trab
Phaco-ECP vs. Phaco-Trab
Lau et al.[22] (mean)		6 months		−3		-6		0.137
Phaco-AIT vs. Phaco-Trab
Ting et al.[19] (mean, SD)		6 months		−2.8 ± 3.2		−7.4 ± 9.7		0.54
		12 months		−2.7 ± 5.3		−6.4 ± 8.7		0.35
Phaco-Xen vs. Phaco-Trab
Parra et al. (mean, 95%CI)[20]		1 day		−5.5 (−9.2, −1.8)		−10.4 (−14.7, −6.2)		0.0122
		1 week		−5.6 (−8.2, −3.1)		− 10.3 (−14.6, −6.0)		0.0173
		1 month		−3.3 (−5.9, −0.6)		−8.4 (−11.7, −5.0)		0.0083
		3 months		−2.8 (−5.5,−0.1)		−7.6 (−11.4, −3.9)		0.0093
		6 months		−4.3 (−6.7, −1.9)		−7.1 (−10.2, −4.0)		0.3623
		12 months		−3.5 (−5.8, −1.1)		−7.3 (−10.7, −4.0)		0.0508
Phaco-ELT vs. Phaco-Trab
Töteberg-Harms et al.[21] (mean, SD)		12 months		−4 (5.8)		−9.8 (4.09)		<0.05
		4 years		−5 (5.8)		−8.8 (4.05)		<0.05

Number of antiglaucomatous medication

Tables 7 and 8 summarize the study findings on the reduction and number of antiglaucomatous medications postoperatively. All four studies reported a significant reduction in antiglaucomatous medication in both groups at postoperative follow-up.[19,20,21,22] Two studies reported a comparable number of antiglaucomatous medications used postoperatively in the Phaco-MIGS and Phaco-Trab groups.[19,20] This differed from the Töteberg-Harms et al. study, where the median amount of drugs used after Phaco-ELT was higher compared with after the Phaco-Trab (1 vs. 0, P = <0.001) in each of the follow-up visits (1 and 4 years postoperatively).[21] At 6 months follow-up, Lau et al. found that the reduction of antiglaucomatous medication number in the Phaco-Trab group was significantly higher than in the Phaco-ECP group (4 vs. 1, P = 0.001).[22]

Table 7.

Antiglaucomatous medication used

Study		Time of follow-up		Number of antiglaucomatous medication				P
				Phaco-MIGS		Phaco-Trab
Phaco-Xen vs. Phaco-Trab
Parra et al.[20]		baseline		2.1		2.4		>0.05
		12 months		0.1±0.3		0.1±0.2		>0.05
Phaco-AIT vs. Phaco-Trab
Ting et al.[19]		baseline		1.8		1.4		0.59
		6 months		0.78±1.39		0.38±0.74		0.68
		12 months		0.44±0.88		0.75±0.89		0.41
Phaco-ELT vs. Phaco-Trab
Töteberg-Harms et al.*[21]		baseline		2		2		0.722
		1 year		1		0		<0.001
		4 years		1		0		<0.001

*Presented in median

Table 8.

Reduction of medication

Study		Time of follow-up		Number of antiglaucomatous medication reduction				P
				Phaco-MIGS		Phaco-Trab
Phaco-ECP vs. Phaco-Trab
Lau et al.[22]		6 months		1		4		0.001

Success rate

Table 9 summarizes the success rate in both treatment groups from the four included studies. Qualified success was awarded if a defined target IOP criteria [Table 3] was achieved and maintained with or without medication in the study participants, whereas in complete success, the target IOP has to be achieved without medication use. Overall, the Phaco-Trab group showed a higher trend of success in comparison to the Phaco-MIGS group for both qualified and complete criteria, although not always statistically significant.[19,21,22] At 1-year and 4-year follow-ups, Töteberg-Harms et al. reported a significantly higher percentage of success in the Phaco-Trab group than in the Phaco-ELT group (P < 0.001).[21] In contrast, when Phaco-AIT was compared with Phaco-Trab, Phaco-AIT demonstrated no statistically significant difference in qualified and complete success (P = 0.14).[19] Lau et al. reported a comparable qualified success rate at 6-month follow-ups (76.2% vs. 71%, P = 0.677) but a statistically higher complete success for the Phaco-Trab group (38.1% vs. 3.2%, P = 0.002).[22] Parra et al. did not report their qualified success findings and found a significantly higher complete success in the Phaco-Trab group (84.6% vs. 62.5%, P = <0.05).[20]

Table 9.

Success rate during follow-up

Study		Criteria		Success rate (%)				P
				Phaco-MIGS		Phaco-Trab
Phaco-ECP vs. Phaco-Trab
Lau et al.*[22]		Qualified successa		71		76.2		0.677
		Complete successa		3.2		38.1		0.002
Phaco-AIT vs. Phaco-Trab
Ting et al.†[19]		Qualified successa		40		37.5		0.14
		Complete successa		20		50
Phaco-ELT vs. Phaco-Trab
Töteberg-Harms et al.†[21]		Qualified success		47a, 34b		95a, 89b		<0.001
		Complete success		18a, 9b		90a, 75b		<0.001
Phaco-XEN vs. Phaco-Trab
Parra et al.[20]		Qualified success
		Complete success		62.5		84.6		<0.05

a: at 1 year, b: at 4 years, *≤15 mmHg/≥30% reduction from baseline, ^†≤21 mmHg/≥20% reduction from baseline

Complication

Ting et al. and Töteberg-Harms et al. reported that most early postoperative period complications were IOP spikes and hypotony.[19,21] IOP spikes were more common in the Phaco-MIGS group than in the Phaco-Trab group in studies; However, Ting et al. found that the difference was not statistically significant (50% vs. 33%, P > 0.05).[19] Töteberg-Harms et al. only found IOP spike incidence in the Phaco-MIGS group (10% vs. 0%, P = 0.017).[21] Conversely, hypotony in the early postoperative period was more common in the Phaco-Trab group in both studies. However, only Töteberg-Harms et al. found this to be statistically significant (22% vs. 4%, P < 0.001). Overall, Ting et al. disclosed that the incidence of early postoperative complications and late postoperative complications in both groups were not significantly different. Severe early postoperative complications, choroidal effusion, and hypotony maculopathy were seen only in the Phaco-Trab group.[19,21]

Discussion

An externo trabeculectomy with antifibrotic agents is the favored surgical intervention for a patient with OAG and cataract when phacoemulsification alone is deemed insufficient to reach the target IOP. It was first successfully described by Cairns et al. in 1968. Since then, there have been several modifications to the procedure to increase its success rate, such as using antifibrotic agents to prevent fibrovascular ingrowth.[23] However, this procedure is invasive and carries many risks, such as choroidal effusion, endophthalmitis, and hypotony maculopathy.[12]

MIGS is a relatively new procedure that might be an alternative to trabeculectomy with better safety properties. Yet, studies on MIGS in combination with Phaco for patients with OAG are sparse. In this review, we included four studies published between 2017 and 2019; all studies were examined for risk of bias by using appropriate tools and showed moderate to excellent quality.[19,20,21,22]

All four included studies noted a significant reduction of IOP compared to baseline and comparable IOP reduction between treatment groups at each follow-up, except for the Phaco-XEN group in the study by Parra et al., which reported a significant difference between treatment groups during early postoperative follow-up to 3 months, which became comparable at 6 and 12 months follow-up.[19,20,21,22] Previous meta-analysis done by Wang et al. of 1602 eyes comparing the effectiveness of Xen implant either alone or in combination with phacoemulsification against trabeculectomy reported a similar finding in which both procedures managed to achieve a significant reduction of antiglaucomatous medication and found that the IOP was comparable.[24] The efficacy of XEN in combination with phacoemulsification might be influenced by the viscoelastic used, where the residues might cause differences in the early postoperative period and gradually diminish.[24] This was also seen in the study by Parra et al., wherein the mean IOP reductions between Phaco-XEN and Phaco-Trab differed significantly up to the 3^rd-month follow-up but remained similar from the 6^th-month follow-up onward (P > 0.05).[20] XEN implant works similarly to trabeculectomy to reduce IOP by shunting the aqueous outflow toward subconjunctival space. Interestingly, XEN possesses several benefits compared with trabeculectomy due to its simpler procedure, smaller incision, stable anterior chamber, less postoperative inflammation, and most importantly, not causing conjunctival injury or scar.[24] With similar efficacy and fewer complications reported, Phaco-XEN might be a promising alternative to treat OAG less invasively.

In our study, the success rates of the Phaco-AIT group reported by Ting et al. at 1-year follow-up were lower (40%) than in previous studies.[19] A possible cause for this is insufficient engagement or reapproximation with the footplate, in addition to other factors such as lower baseline IOP, younger age, and BMI >25 kg/m².[25,26] In contrast, our included comparison of Phaco-ECP and Phaco-Trab by Lau et al. revealed a comparable IOP reduction and success rate between the two groups (P > 0.05).[21] This finding aligns with the only RCT ever done comparing the two interventions of 58 eyes by Gayton et al. In addition to similar IOP reduction and success rate profile, they reported a similar antiglaucomatous medication reduction.[27]

According to the study by Töteberg-Harms et al., Phaco-Trab showed significantly higher qualified and complete success rates at 1 and 4 years postoperatively than Phaco-ELT. Despite this, their other findings revealed a significant IOP reduction from baseline in eyes having Phaco-ELT, with constant results after a year of follow-up, and no severe complication was reported except for a mild anterior chamber reaction.[28] This is corroborated by a review by Durr et al. showing significant IOP reduction with minimal complications, including IOP spikes and hyphema, which can be resolved without complicated measures.[29]

The use of antifibrotic agents in trabeculectomy to increase its success rate may lead to an increased incidence of bleb-related infections.[25,26,30,31] Studies have reported an incidence rate of endophthalmitis after filtration procedures with antifibrotic agents between 1.1% and 3%.[25,26,31] A thinner bleb wall due to the use of antifibrotic agents may lead to bleb leak, which is a predisposing factor for infection from the transconjunctival spread of the organism.[30]

Overall, in our included studies, we found that the Phaco-MIGS group reported fewer complications compared to the Phaco-Trab. Possibly because of a restricted number of studies and eyes, no post-intervention infection was reported in both groups from the four studies included.[19,20,21,22] Although the report of endophthalmitis post Phaco-MIGS is scarce compared to Phaco-Trab, previously, severe endophthalmitis had been reported in a patient who underwent Phaco-MIGS using IStent injection.[32] Nevertheless, the risk of infection must be acknowledged by surgeons in either intervention.

Overall, the Phaco-MIGS group reported fewer complications, such as hypotony, choroidal hemorrhage, inflammation, and lower anterior chamber reaction incidence, than the Phaco-Trab group, which aligns with previous studies.[27,33,34] In the Phaco-AIT group, there is no bleb formation and no device is left in the eye, thus reducing the perpetual risk of infection. The low incidence of severe complications reported in the study by Ting et al. was consistent with previous studies, in which out of approximately 10,902 reported cases, hypotony made up 0.09% of all reported cases, choroidal hemorrhage 0.01%, and endophthalmitis 0.01%.[19,33,34]

Due to the limited number of available studies on the topic, the population in our included studies was pretty small at 259 OAG eyes from four studies with different types of MIGS.[19,20,21,22] There was also a varying definition of target IOP used as success criteria between studies: whereas two studies (Ting et al. and Töteberg-Harms et al.) used ≤21 mmHg or ≥20% reduction from baseline based on a prior study by Gedde et al., one study by Lau et al. used ≤15 mmHg or ≥30% reduction from baseline as their criteria.[19,21,22,35] These factors might influence the interpretation of the overall success rates reported in our study and imply that the success rate in the Lau et al. study might be higher than reported.[22] IOP baselines differed between the Phaco-MIGS and Phaco-Trab eyes in the study by Lau et al. and Töteberg-Harms et al., thus affecting the result interpretation.[21,22] There was a risk of population bias in studies included, with a homogenous racial profile as most participants were Caucasians, while Asians were rarely reported. The differences in conjunctival cell profile and racial differences might influence the pigmentation of ciliary epithelium, which may affect the result of the MIGS procedure. This racial influence has also been studied by Husain R et al. but reflects its effect only on trabeculectomy eyes.[36]

Furthermore, RCTs should be done for each type of MIGS available in combination with phacoemulsification, comparing it to Phaco-Trab. Future studies should include more Asian populations with robust IOP criteria and OAG definition at baseline.

Conclusion

Phaco-MIGS, particularly Trabectome, offer a good option for individuals with OAG and concomitant cataracts, showing a comparable outcome to Phaco-Trab. Complications are comparable in both groups, although severe complications such as hypotony, maculopathy, and choroidal effusion were only observed in the Phaco-Trab group. Further studies through RCT are needed to validate these findings.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.