Systematic review and meta-analysis of the clinical effectiveness, safety, humanistic and economic burden of the OMNI^® surgical system and its predecessors

Abstract

Objective

The aim of this systematic review and meta-analysis was to assess the clinical, humanistic, and economic evidence of the OMNI^® Surgical System (OMNI), Visco360 and Trab360 for open-angle glaucoma (OAG).

Methods

Search strategies were applied across MEDLINE^®, Web of Science™, Cochrane (January 2016–April 2024) on 16th April 2024. Congress proceedings (2021–2024) were searched in July 2024. Studies containing ≥15 patients that reported clinical, humanistic or economic outcomes associated with the use of OMNI, Visco360 or Trab360 for the treatment of adults with OAG were included. Structured summaries were used to summarize findings and a meta-analysis synthesized the data. Risk of bias was assessed using the Newcastle-Ottawa and CHEERS checklists. The protocol was registered on PROSPERO (CRD42024536680).

Results

Among 29 included publications, 27 reported clinical and 2 reported economic outcomes. OMNI significantly reduced intraocular pressure (IOP) with mean IOP <18 mmHg (11.5–17.2 mmHg) at 12 months when used standalone or combined with cataract surgery. The meta-analysis confirmed statistically significant, comparable IOP reductions at months 6, 12 and 24. IOP-lowering medication use decreased from 0.9–3.4 at baseline to 0.1–2.2 at month 12 (standalone and combination); these continued months 24–36. Adverse events were generally mild and transient.

Conclusion

OMNI consistently reduced IOP and medication use demonstrating sustained effects over 24­–36 months with a favorable safety profile, thus supporting its use in patients with OAG. Limitations of this review include the absence of randomized controlled trials. Six studies were assessed as good quality, the remainder showed risk of bias.

Introduction

Globally, glaucoma is the second leading cause of blindness, and the primary cause of irreversible blindness. ¹ The only modifiable risk factor for glaucoma is elevated intraocular pressure (IOP) ² and long-term data have demonstrated that an IOP <18 mmHg is associated with little or no change in visual field (VF) defect. ³ Adult glaucoma can be classified into open-angle (OAG) and closed-angle. ⁴ In OAG, the anterior chamber angle appearance is normal. Raised IOP is caused by resistance in the trabecular meshwork outflow pathway. ⁵ The extent of glaucoma ranges from suspected or pre-perimetric glaucoma with largely undetected VF deficits, to advanced disease which threatens the central VF. The Hodapp-Parrish-Anderson method is commonly used to classify glaucoma, with mild glaucoma mean deviation (MD) of VF loss between zero and −6 dB; moderate MD −6.01 to −12 dB; and advanced MD worse than −12.01. ⁶

Accounting for >70% of cases, the most common form of glaucoma is primary OAG (POAG). ⁷ In a 2021 analysis, the global prevalence of POAG was 2.4% in people aged >40 years (95% confidence interval [CI], 2.0–2.8%), resulting in an estimated 68.56 million cases. ⁸ In the United States (US), glaucoma imposes an economic burden of approximately $2.9 billion annually (2004 data and costs). ⁹

Previously, management of IOP typically began with pharmaceutical options (i.e., eye drops), laser procedures, and finally filtration surgery. ¹⁰ Recent developments have led to a transformative change in the use of selective laser trabeculoplasty as a first-choice intervention. ¹¹ Furthermore, minimally invasive glaucoma surgery (MIGS) may be considered for patients with early glaucoma, ⁵ or those with inadequately controlled IOP following medical therapy or laser procedures.^12,13 MIGS can be performed alone or in combination with cataract surgery.^12,13 MIGS techniques involve minimal tissue manipulation, thus enabling a faster recovery with fewer complications versus filtration surgery. ⁵

The OMNI^® Surgical System is a MIGS device that has a conformité européenne (CE) mark for the catheterization and transluminal viscodilation of Schlemm's canal and the cutting of trabecular meshwork to reduce IOP in adult patients with OAG. ¹⁴ In 2017, the US Food and Drug Administration (FDA) cleared OMNI for delivery of small amounts of viscoelastic fluid and indicated OMNI to cut trabecular meshwork tissue during trabeculotomy procedures. ¹⁵ In 2021, this indication was extended to canaloplasty (microcatheterization and transluminal viscodilation of Schlemm's canal) followed by trabeculotomy (cutting of trabecular meshwork) to reduce IOP in adult patients with POAG. ¹⁶ OMNI combines the procedures performed by previous iterations (Visco360 and Trab360).

Glaucoma surgery has rapidly evolved in the last five years, however published data supporting the use of specific techniques has lagged. The selection of a MIGS approach that maximizes effectiveness whilst maintaining safety is a priority, and evidence is needed to support these decisions. ¹⁷ Use of OMNI has been rapidly increasing,^18–20 however, new clinical, humanistic, and economic data have not been systematically reviewed. Therefore, a systematic review (SR) and meta-analysis were conducted to comprehensively assess the latest clinical, humanistic and economic evidence for OMNI to support clinical decision making.

Methods

This SR was conducted in accordance with standard methodology endorsed by Cochrane and reported in accordance with Preferred Reporting Items for SRs and Meta-Analyses (PRISMA) guidelines. The protocol was registered on PROSPERO (CRD42024536680). Minor amends were made to the initial protocol registered with PROSPERO. These included adjustments to the inclusion criteria to minimize any ambiguity or discrepancies in interpretation between reviewers. SRs were also removed from the inclusion criteria for study design. Instead, relevant SRs identified during the search process were examined to identify potential primary studies that may meet the inclusion criteria of this SR. Bibliographies of the included studies were also be reviewed to obtain further relevant references.

Search strategy

A comprehensive search was conducted across three electronic databases including MEDLINE^® (via PubMed.com), Web of Science™ (via Clarivate), and Cochrane Database of SRs & Cochrane Controlled Register of Trials (via Cochrane Library). The search was run on 16^th April 2024 and a grey literature search was conducted in July 2024. Selected conference proceedings were searched including the American Academy of Ophthalmology (AAO), American Glaucoma Society (AGS), International Society for Health Economics and Outcomes Research (ISPOR), American Society of Cataract and Refractive Surgeons (ASCRS) and European Glaucoma Society (EGS). Articles published between January 2016–April 2024 and conference presentations published 2021–2024 were included. The full search strategy can be found in Supplemental Materials 1.

Eligibility criteria

During the study selection process, retrieved publications were evaluated against the pre-determined Population, Intervention, Control, Outcomes, Study design and Timeframe (PICOS-T) criteria (Table 1).

Table 1.

Full PICOS-T criteria for the SR.

Criteria	Inclusion criteria	Exclusion criteria
Population	Adults (≥18 years) patients diagnosed with OAG (≥80% of involved patients diagnosed with OAG) Studies with ≥15 patients with OAG	Studies evaluating patients with diseases other than OAG Studies primarily involving patients with other types of glaucoma (e.g., angle-closure glaucoma, normal-tension glaucoma) without a significant proportion (≥80%) of patients diagnosed with OAG Animals/in-vitro studies Studies with <15 patients with OAG
Intervention	Studies focusing on the following interventions of interest: OMNI (and previous iterations Visco360 and Trab360)	Studies evaluating OMNI used in combination with other devices (e.g., Hydrus)
Comparator	Any comparator, no comparator	Not applicable
Outcomes	Studies reporting the following outcomes for the population of interest: Clinical outcomes • IOP effects o Mean IOP at follow up (mmHg) o Average percent and absolute IOP reduction (% or mmHg) o Any definition of IOP treatment success or failure in included studies e.g., patients with a ≥ 20% reduction in mean IOP from baseline, IOP ≤18 mmHg at 12 months without anti-glaucoma medications* o Use of another IOP lowering procedure e.g., trabeculectomy, deep sclerectomy • Use of medication (average percent, absolute change from baseline, number of patients/eyes medication free) • Secondary surgical intervention† • AEs (type and frequency of AEs, number of patients/eyes affected) Economic outcomes • Direct and indirect costs e.g., procedure cost, healthcare resource use (currency, year) Humanistic outcomes • QoL e.g., quality adjusted life years, utility scores	Studies not reporting any of the outcomes of interest
Study Design	Randomized controlled trials, single-arm trials Observational studies Cross-sectional studies Case series	Editorials/commentaries Case-reports Narrative reviews SRs and/or meta-analysis
Timeframe	Studies published January 2016–16 April 2024; conference presentations published 2021–July 2024	Studies published before 2016

AE, adverse events; IOP, intraocular pressure; OAG, open-angle glaucoma; QoL, quality of life; SRs, systematic reviews. *Note that the definition of treatment success or failure varied between publications. ^†Secondary surgical intervention is reported in Supplemental Materials 2.

Study selection and extraction

Titles and abstracts identified from the database searches were reviewed by two independent reviewers (AS, FG) to assess suitability according to the PICOS-T pre-defined inclusion and exclusion criteria. For titles and abstracts that were included, full-text articles were retrieved and reviewed against the eligibility criteria by the two independent reviewers. Disagreements between reviewers were resolved by a third reviewer (PB). Data from included studies was extracted into a data extraction template in Microsoft Excel™. Outcomes extracted included IOP effects (such as mean IOP at follow up and absolute mmHg IOP reduction), use of IOP lowering medication, treatment success or failure, adverse events (AEs), secondary surgical intervention, direct and indirect costs, cost drivers and quality of life (QoL). The most common definition of treatment success from included studies was an IOP reduction ≥20% from baseline, therefore we used this definition for this outcome. Structured summaries were used to synthesize and summarize the data for each outcome.

Risk of bias assessment

Studies were assessed for quality using standard quality appraisal checklists depending on publication type by two independent reviewers. Cochrane Risk-of-Bias 2.0 was proposed for randomized controlled trials (RCTs) and the Critical Appraisal Skills Programme Checklist for SRs. As no gold-standard tool exists to assess the quality of non-randomized studies, the Newcastle-Ottawa Scale was selected ²¹ as it is an established, widely used method. ²² Economic analyses were appraised using the Consolidated Health Economic Evaluation Reporting Standards (CHEERS) checklist. ²³

Meta-analysis

A random-effects meta-analysis was performed to synthesize data from the SR (Supplemental Materials 3). The unit of analysis was the number of patients. Four subgroups of patients were examined; OMNI stand-alone versus OMNI combined with cataract surgery; and OMNI in patients with a baseline IOP ≥18 mmHg versus <18 mmHg. Timepoints analyzed were 6, 12, 24 and 36 months. Effect sizes included IOP reduction, number of medications, percentage of medication-free patients, and patients with treatment success (IOP reduction ≥20% from baseline).

Standardized mean difference (SMD) was used to measure effect size for IOP due to variations in the measurement scales and methods across the included studies. Although IOP is typically reported in mmHg, differences in baseline values, instruments, and reporting formats (e.g., change-from-baseline vs. final values) introduced heterogeneity that made direct comparison of raw mean differences challenging. Using SMD allowed us to standardize the effect sizes across studies and reduce the impact of these methodological differences. A restricted maximum-likelihood estimator was utilized to estimate between-study variance (tau-squared). The Q-Profile method was employed to calculate 95% CI for tau-squared and tau, offering insights into the uncertainty of variance. Heterogeneity was assessed using the I-squared and Q-statistical tests. Studies were assessed for publication bias. All meta-analyses were conducted using R software (version 4.3.3; R Foundation for Statistical Computing, Vienna, Austria). The analyses were performed using the meta and metafor packages.

Results

Search results

In total 94 publications were identified (Figure 1). Twenty-nine publications of 22 unique studies, including over 2,375 eyes (Supplemental Materials 4).

Figure 1.

PRISMA flow diagram.

Study characteristics

Among the 22 unique studies, 14 were retrospective, six were prospective and two were health economic evaluations. The majority of studies were conducted in the US (17 studies)^{18,20,24–38}; the remainder were conducted in Europe (4 studies)^19,39–41 and Asia (1 study). ⁴² Eleven studies assessed OMNI in combination with cataract surgery,^{18,24,27,29,31,33,34,36–38,42} four assessed standalone OMNI surgery,^25,26,32,39 and seven studies assessed both combination and standalone OMNI surgery.^{19,20,28,30,35,40,41} Follow-up periods ranged from 6–36 months; median follow up duration was 12 months (8 studies).

Study population

Sample sizes ranged from 17 to 541 eyes. Thirteen studies predominantly enrolled eyes with mild-to-moderate OAG,^{19,20,25–30,33,35,39–41} while six studies included severe OAG.^{18,24,31,36–38} Glaucoma severity was unspecified in three publications,^32,34,42 and the scales used to determine glaucoma severity were different across studies, which could affect the generalizability of findings. Five studies categorized patients according to baseline IOP, using thresholds of ≥18 mmHg and <18 mmHg.^{18,31,33,35,40}

Clinical, humanistic and economic outcomes

Clinical efficacy

IOP reduction

Twenty-seven publications reported clinical outcomes (Table 2). Baseline IOP ranged between 14.1 ⁴³ and 28.8 mmHg. ⁴² A reduction in IOP was demonstrated at months 6, 12, and 24, and this trend continued to month 36. Studies comparing standalone OMNI surgery and OMNI in combination with cataract surgery showed similar clinical effectiveness with no significant differences in IOP reduction between groups.

Table 2.

Clinical outcomes (change in IOP and medication use) at month 12.

Author, year	Total patients enrolled (eyes at follow up)	Baseline IOP (mmHg), mean (SD) or [SE]	IOP (mmHg) at month 12, mean (SD) or [SE]	Absolute change from baseline (mmHg) [%]	No. of medications at baseline, mean (SD) or [SE]	No. of medications at month 12, mean (SD) or mean [SE]	No. of patients medication free at month 12, n (%)
Standalone and combination cohort
Grabska-Liberek 2022 19	15 (14)	20.4 [1.1]	12.7 [0.5]	−7.3 [-36%]	2.6 [0.2]	0.6 [0.2]	7 (41.2%)
Hughes 2020 28	64 (72)	24.5 (8.3)	16.5 (3.4)	-8.0* [-37.7%]*	2.5 (1.3)	1.8 (1.4)	NR
Murphy 2022 20	136 (136)	22.3 (3.7)	15.9 (4.4)	-6.4 [-28.6%]	1.9 (1.3)	1.3 (1.2)	41 (30.0%)
Ondrejka 2019 40	130 (72)†	24.6 (7.1)	14.6 (2.8)	-10.0* [-41.0%]	2.1 (1.0)	0.2 (0.6)	85.0%
	130 (34)‡	14.9 (1.8)	13.6 (2.3)	-1.3* [-8.7%]*	1.8 (0.9)	0.2 (0.6)	88.0%
Toneatto 2022 41	73 (66)	22.5 (5.3)	15.0 (3.6)	-6.9 [-29%]	3.2 (1.0)	1.9 (1.4)	NR
Standalone cohort
Grabska-Liberek 2022 19	15 (6)	22.1 [1.6]	13.3 [1.1]	-8.7 [-39%]	2.6 [0.2]	0.7 [0.2]	NR
Hughes 2020 28	64 (11)	NR	NR	-7.1	NR	NR	NR
Klabe 2021 39	27 (30)	24.6 (3.0)	14.7 (1.6)	-10.1 [-39.8%]	1.9 (0.7)	0.4 (0.6)	63.0%
Ondrejka 2019 40	130 (11)†	28.8 (6.4)	14.5 (3.6)	-14.3 [-49.7%]*	3.0 (1.3)	0.8 (1.1)	NR
Williamson 2023 35 # Vold 2021 17 #	72 (24)§	21.8	15.6	-6.2* [-27.1%]	1.7 (1.3)	1.2 (1.3)	9 (37.5%)
	48 (24)ǁ	15.4	13.9	-1.5* [-10.2%]	2.0 (1.3)	1.3 (1.3)	6 (31.6%)
Sarkisian 2019 32	69 (44)	23.7	15.7	-7.3 [-33.8%]*	1.7	1.1	NR
Toneatto 2022 41	73 (40)	23.0 (5.7)	15.6 (3.6)	-6.5 [-26.8%]	3.0 (1.1)	2.0 (1.4)	NR
Combination cohort
Chen 2020 42	34 (40)	28.8 (7.0)	11.5 (2.3)	-17.3* [-60.1%]*	2.6 (0.7)	0.1 (0.3)	NR
Gallardo 2022a 27	149 (120)	23.9 (3.0)	15.6 (4.0)	-8.2 [-34.7%]*	1.8 (0.9)	0.3 (0.9)	98 (82.0%)
Grabska-Liberek 2022 19	15 (8)	18.5 [1.1]	12.3 [0.5]	-6.3 [-34%]	2.6 [0.3]	0.6 [0.3]	NR
Hughes 2020 28	64 (31)	NR	NR	-7.5	NR	NR	NR
Mbagwu 2024 31	428 (541)	16.5 (4.9)	NR	-1.7	2.0 (1.0)	NR	90 (32.8%)
	428 (153)§	NR	NR	-7.0	NR	NR	NR
	428 (388)ǁ	NR	NR	-0.1	NR	NR	NR
Noh 2024 38	29 (12)¶	17.6 (5.2)	13.3 (2.8)	-4.3* [-24%]	2.2 (1.3)	1.3 (1.5)	NR
	29 (12)Δ	17.6 (4.6)	13.1 (2.2)	-4.5* [-26%]	2.4 (1.3)	2.2 (1.6)	NR
Ondrejka 2019 40	130 (61)†	23.8 (6.9)	14.6 (2.6)	NR [-38.7%]*	1.9 (0.8)	0.1 (0.5)	NR
Williamson 2023 35 # Hirsch 2021 43 #	72 (24)§	21.9 (3.7)	15.1 (3.7)	-6.8* [-30.2%]	2.0 (1.3)	1.1 (1.1)	8 (33.3%)
	81 (57)ǁ	14.1 (2.5)	13.4 (3.1)	-0.9* [-3.8%]	1.6 (1.3)	0.9 (1.2)	26 (49.1%)
Smith 2024 18	33 (42)	17.2 [4.8]	13.4 [2.4]	-3.8* [-22.3%]	2.4 [1.2]	1.7 [1.6]	NR
	12 (15)†	22.2 [4.6]	14.3 [2.8]	-7.9* [-35.4%]	2.5 [1.5]	2.0 [1.8]	NR
	21 (27)‡	14.4 [1.8]	12.8 [2.0]	-1.6* [-11.4%]	2.3 [1.1]	1.6 [1.5]	37.0%
Toneatto 2022 41	73 (26)	21.5 (4.7)	14.1 (3.3)	-7.6 [-32.4%]	3.4 (0.8)	1.9 (1.4)	NR
Tracer 2020 33	130 (111)†	23.0 (5.5)	17.2 (5.1)	-5.2* [-22%]	0.9 (0.9)	1.0 (0.9)	32.0% of eyes
	130 (69)‡	14.3 (2.3)	15.4 (4.1)	+1.1* [7.7%]*	1.1 (0.9)	0.6 (0.6)	47.0% of eyes
Yadgarov 2023 37	128 (128)	17.2	14.3	-2.9* [-16.9%]	1.3	0.8	NR

NR, not reported; SD, standard deviation; SE, standard error. *Calculated manually. **Diurnal IOP.

^§Baseline IOP >18 mmHg. ^ǁBaseline IOP ≤18 mmHg. ^†Baseline IOP ≥18 mmHg; ^‡Baseline IOP <18 mmHg ^#Please note that Williamson 2023, Vold 2021 and Hirsch all report findings from the ROMEO study. ROMEO included pseudophakic patients undergoing standalone OMNI as well as patients undergoing OMNI combined with phacoemulsification cataract surgery. Vold 2021 only reports patients who underwent OMNI, Hirsch 2021 reports patients who underwent OMNI and cataract surgery, and Williamson 2023 reports both, thus why these are reported in different categories. ^¶Patients who underwent the procedure in the superior direction; ^ΔPatients who underwent the procedure in the inferior direction.

OMNI effectively reduced IOP in the subgroup patients with baseline IOP ≥18 mmHg, while maintaining IOP control in those <18 mmHg.

At month 12, IOP was reduced by 5.2–14.3 mmHg from baseline in patients with IOP ≥18 mmHg, and +1.1–1.6 mmHg in patients with IOP <18 mmHg. In the subgroup of patients who received standalone OMNI surgery, IOP was reduced by 6.2–14.3 mmHg in patients with ≥18 mmHg, and 1.5 mmHg in patients with <18 mmHg. In the combination subgroup, IOP was reduced by 5.2–7.9 mmHg in patients with ≥18 mmHg, and +1.1–1.6 mmHg in patients with <18 mmHg.

At month 24, IOP was reduced by 6.1–7.4 mmHg from baseline in patients with IOP ≥18 mmHg and 0.5–2.3 mmHg in patients with ≤18 mmHg. In the standalone OMNI subgroup, IOP was reduced by 7.4 mmHg from baseline in patients with IOP ≥18 mmHg, and 2.3 mmHg in patients <18 mmHg. In the combination subgroup, IOP was reduced by 6.1–6.6 mmHg in patients with ≥18 mmHg and 0.5–0.6 mmHg in patients with <18 mmHg.

One study reported IOP reduction at month 36 in patients who received standalone OMNI or in combination with cataract surgery. IOP was reduced by 5.8 mmHg (mean change from baseline) at month 36. ⁴⁵ In the subgroup patients with baseline IOP <18 mmHg, this study reported maintenance of IOP control at month 36 (15.4 mmHg, baseline; 13.9 mmHg, month 36). ⁴⁵

Medication use

At baseline patients were using 0.9–3.4 medications. At month 6, no patient received more than two medications in any study. At month 12, medication use ranged from 0.1–2.2 medications, and at month 24 the range narrowed further to 0.5–1.6 medications (Table 2 and Table 3). The rate of patients who were medication-free ranged from 34.2–78% at month 6,^31,46 to 74% at month 36. ⁴⁴ Four studies reported medication washout prior to surgery.^25–27,39 The rate of patients who were medication-free following washout was 82% at month 12, ²⁷ and up to 67% at month 24. ²⁵ Patients with medication washout received fewer medications at months 6 (0.3 ³⁹ versus 0.5–1.7^19,41), 12 (0.4 ³⁹ versus 0.7–2.0^19,41) and 24 (0.5–0.7^25,39 versus 1.2–1.6 ³⁵ ) compared to patients without washout prior to standalone OMNI surgery. Changes in medication reduction between standalone and combined treatments are presented in Supplemental Materials 5.

Table 3.

Clinical outcomes (change in IOP and medication use) at month 24.

Author, year	Total patients enrolled (eyes at follow up)	Baseline IOP (mmHg), mean (SD)/ Mean [SE]	IOP (mmHg) at month 24, mean (SD)/ Mean [SE]	Absolute change from baseline (mmHg) [%]	No. of medications at baseline, mean (SD)/ Mean [SE]	No. of medications at month 24, mean (SD)/ Mean [SE]	No. of patients medication free at month 24, n (%)
Standalone and combination cohort
Williamson 2023 35	72 (39)	NR	NR	NR	NR	1.3	33.3%
Standalone cohort
Flowers 2024 25	17	26.1 (4.0)	16.0 (3.4)	−10.1* [-39%]	2.1 (1.0)	0.7	67.0%
Klabe 2021 39	27 (26)	24.6 (3.0)	14.9 (2.0)	-10.0 [-39.6%]	1.9 (0.7)	0.5 (0.7)	58.0%
Williamson 2023 35	17 (17)§	22.1	14.7	-7.4 [-33.5%]*	1.9	1.6	NR
	12 (11)ǁ	15.6	13.3	-2.3* [-14.7%]*	2.2	1.2	NR
Combination cohort
Chen 2020 42	34 (40)	28.8 (7.0)	11.5 (2.28)	-17.3* [-60.1%]*	2.6 (0.7)	0.1 (0.3)	NR
Greenwood 2023 44	66 (66)	23.1 (2.7)	16.7 (4.1)**	-6.2 [-27%]	1.6	0.4 (0.9)	51 (77.0%)
Mbagwu 2024 31	428 (225)	16.5 (4.9)	NR	-2.3	2.0 (1.0)	NR	134 (59.6%)
	428 (NR)§	NR	NR	-6.6	NR	NR	NR
	428 (NR)ǁ	NR	NR	-0.5	NR	NR	NR
Williamson 2023 35	17 (15)§	21.7	15.6	-6.1 [-28.1%]*	2.2	1.4	NR
	26 (24)ǁ	14.3	13.7	-0.6* [-4.2%]*	1.9	1.2	NR
Yadgarov 2023 37	71 (71)	17.2	14.0	NR [-18.2%]	1.3	0.9	NR

NR, not reported; SD, standard deviation; SE, standard error. *Calculated manually. **Diurnal IOP.

^§Baseline IOP >18 mmHg; ^ǁBaseline IOP ≤18 mmHg.

Treatment success

Treatment success was defined as an IOP reduction ≥20% from baseline as this was a commonly used definition in included studies. Three studies reported treatment success at month 6 ranging from 97.4–100% (Supplemental Materials 6).^18,27,39

Safety

Thirteen studies reported at least one AE (Supplemental Materials 2).^{18–20,24,32,33,35,37,39–41,46,47} Most AEs were mild with no serious AEs reported.

Meta-analysis

The meta-analysis revealed that both standalone and combination surgery with OMNI effectively reduce IOP, and medication use from baseline over various timeframes (Figure 2(A), (B) and (C) and Figure 3(A) and (B), Supplemental Materials 5–8). At 6 and 12 months, changes in IOP from baseline were comparable between OMNI standalone and combination procedures (Figure 2(C)). Significant reductions were maintained up to 24 months for OMNI in combination with cataract surgery. The meta-analysis showed a small overall effect size, with high heterogeneity among included studies, potentially due to differences in study populations, interventions, baseline IOP levels and follow-up durations.

Figure 2.

A. IOP reduction from baseline at 6 and 12 months (OMNI standalone surgery). B. IOP reduction from baseline at 6, 12 and 24 months (OMNI in combination with cataract surgery). C. IOP reduction from baseline at 6 and 12 months (OMNI standalone and in combination with cataract surgery). CI, confidence interval; SD, standard deviation; SMD, standardized mean difference.

Figure 3.

A. Medication reduction from baseline by standalone treatment at 6 and 12 months. B. Medication reduction from baseline by combined therapy at 6, 12 and 24 months. CI, confidence interval; SD, standard deviation; SMD, standardized mean difference.

Patients with baseline IOP ≥18mmHg showed significantly reduced IOP at months 6, 12, and 24 following treatment. Patients with IOP <18 mmHg also showed significantly reduced IOP at months 6 and 12. The meta-analysis demonstrated a moderate and statistically significant negative overall effect size (Supplemental Materials 7). Subgroup analyses at 6 and 12 months showed negative effect sizes with no significant differences, suggesting similar levels of IOP reduction at these time points. High heterogeneity was observed within subgroups, potentially due to differences in study populations, interventions, baseline IOP levels, and follow-up durations.

At 6 and 12 months, 66–68% of patients treated with standalone or combined surgery remained medication-free.^{19,26,27,31,39,40,46} OMNI standalone surgery significantly reduced medication use at months 6 and 12 (Figure 3(A)). Combination procedures significantly reduced medication use at months 6, 12 and 24 (Figure 3(B)). Patients with baseline IOP ≥18 mmHg showed a similar reduction in medication use from baseline to month 12 compared to those with IOP <18 mmHg.

Treatment success (defined as an IOP reduction ≥20% from baseline) was observed in approximately 89% of patients treated with either standalone or combined therapy (see Supplemental Materials 6).^{18,20,26,27,39} At months 6, 12, and 24, 99%, 83% and 93% of patients demonstrated treatment success respectively, showing a strong treatment effect.

Overall, the meta-analysis demonstrates that OMNI is effective in achieving significant reductions in IOP and medication use, with sustained improvements over 6–24 months.

Economic outcomes

Two economic analyses examined cost outcomes associated with OMNI.^29,48 Both analyses were conducted from a US payer perspective using 2022 Medicare tariffs. A budget impact model found that increasing the adoption of OMNI resulted in budget neutrality over two years. Per member per month costs remained unchanged when used without cataract surgery and yielded cost savings of -$0.01 with cataract surgery. ⁴⁸ A cost-utility analysis compared OMNI to iStent inject^® (Glaukos, Aliso Viejo, US) in patients with mild-to-moderate POAG. ²⁹ OMNI was cost-effective compared to iStent inject when combined with cataract surgery over a lifetime horizon ($552 USD lower costs, gain of 0.02 quality-adjusted life years [QALY]). The analysis concluded that OMNI was less costly and more effective than iStent inject.

Humanistic outcomes

The cost-utility analysis included QoL outcomes in the form of QALYs. The average QALYs per patient treated with OMNI were 8.95 over a lifetime horizon and 1.59 over two years, compared with 8.93 and 1.58 for iStent inject. ²⁹ The slightly higher QALYs for OMNI were attributed to its favorable AE profile.

Risk of bias

As no RCTs were identified and SRs were subsequently excluded from the search, quality assessment using the Cochrane Risk-of-Bias 2.0 and Critical Appraisal Skills Progamme Checklist were not conducted. Four studies were considered good quality following assessment with the Newcastle-Ottawa scale (see Supplemental Materials 9).^17,20,31,43 The remaining studies showed risk of bias due to being single-cohort studies or due to significant loss of patients during follow-up. The economic evaluations scored 21 and 22 points out of 28 on the CHEERS checklist, indicating robust methodologies.^29,30

Discussion

This SR and meta-analysis assessed the published evidence relating to clinical, safety, humanistic, and economic outcomes in studies that evaluated OMNI in patients with OAG. OMNI demonstrated a favorable efficacy and safety profile over periods up to 36 months and is thus a beneficial long-term treatment option for patients with OAG. In the meta-analysis, a significant reduction in IOP was observed following surgery using OMNI both as a standalone approach and when combined with cataract surgery.

Low IOP is associated with reduced progression of VF defect. Data from the Advanced Glaucoma Intervention Study (AGIS) showed that eyes presenting with IOP <18 mm Hg at all study visits showed reduced progression in VF defect over 6 years with mean changes from baseline close to zero. ³ An effective intervention therefore needs to reduce IOP below this threshold.

At month 12 following the use of OMNI and cataract surgery, mean IOP ranged from 11.5–17.2 mmHg.^33,42 Significant IOP reductions were also observed at months 6 and 12 in patients with a baseline IOP <18 mmHg. High heterogeneity was observed at months 6 and 12, suggesting variability across studies, potentially due to differences in study populations, interventions, baseline IOP levels, and follow-up durations, however there was no strong evidence of publication bias. In this SR, when OMNI was used as a combined procedure in patients with baseline IOP <18 mmHg, IOP was 13.3–13.9 mmHg at month 6, 12.8–15.4 mmHg at month 12, 13.7–14 mmHg at month 24 and 13.9 mmHg at month 36, demonstrating long-term maintenance of IOP control well below the 18 mmHg-threshold. In a real-world evidence study of 171 eyes, OMNI also maintained a significant IOP reduction in patients with a mean baseline IOP <18 mmHg up to 24 months (13.6 mmHg and 13.0 mmHg at months 12 and 24, respectively, p < 0.001). ³⁷ In this SR, when OMNI was used as a combined procedure in patients with baseline IOP ≥18 mmHg, IOP was maintained between 11.5 and 16.7 mmHg^35,42,44 at month 24, and 16.3 mmHg at month 36. ⁴⁴ A 2024 post-hoc analysis of the ROMEO study suggested that meaningful reductions in IOP and medication use can be expected following treatment with OMNI in eyes with mild, moderate and advanced VF loss. ⁴⁹ Similar results were reported by Yadgarov et al. ³⁷ Thus, OMNI procedures have a strong evidence base as an effective treatment for lowering IOP across a wide variety of patient populations.

High rates of medication-free patients indicate that OMNI can reduce the need for medication, reducing the burden of treatment, potentially improving patient adherence and QoL. In patients with medication washout, the rate of patients who were medication-free were higher at month 12 versus those without (82% ²⁷ vs 49.1% ⁴³ ), supporting the benefit of medication washout prior to surgery. Patients with baseline IOP <18 mmHg also showed a significant reduction in medication use at month 12. The high rates of treatment success observed over 24 months (∼89%) further validate the efficacy of OMNI in maintaining IOP reductions. Some studies reported that patients required SSIs to further reduce IOP following OMNI. However, in 9 of 12 studies reporting SSIs, this affected less than 10% of study participants. The occurrence of SSIs highlights the importance of identifying suitable patients and post-operative management to ensure long-term success.

The most frequently reported AEs were hyphema (mostly self-resolving) and IOP spikes, which are the most common complications associated with this category of MIGS. ⁵⁰ There was no consistent definition of hyphema and infrequent reporting of hyphema severity across studies (Supplemental Materials 2). To minimize the risk and extent of hyphema and associated complications, it is advisable to leave the anterior chamber pressurized after surgery, thus tamponading any sources of hemorrhage (i.e., adding balanced salt solution and ensuring a water-tight wound at the end of surgery). Additionally, OMNI's ab-interno approach leaves the conjunctiva uncompromised which is crucial for successful prospective future filtration surgery.

Limitations of this SR include the absence of randomized controlled trials. These types of trial are challenging to perform with surgical procedures, which may explain why none were identified. Studies varied in terms of their geographical location, patient population and follow-up periods. Whilst not a limitation, the search was limited to studies with a sample size of ≥15 patients with OAG. Appropriate sample sizes guarantee the generation of valid data within clinical studies. Considering that studies involving medical devices used in a surgical environment often have smaller sample sizes, the cut-off (n = 15) was chosen to balance a large enough patient population to reduce the bias and variability that can be associated with smaller studies while still including as many studies as possible. The majority of the included studies were conducted in the US (17 studies). This geographical distribution suggests a focus on the US healthcare context which may influence the generalizability of the findings to other regions, however the US healthcare context reflects the population which is heterogenous. A limitation of the meta-analysis is that no formal sensitivity analyses was performed because the number of included studies per outcome was limited in some cases. However, there were no extreme outliers or inconsistencies that would suggest undue influence from individual studies.

To substantiate the current clinical findings, future research beyond 24 months in different healthcare settings and additional subpopulations, e.g., other common forms of OAG such as pseudoexfoliation, steroid-induced, or pigment dispersion glaucoma, would be advantageous. Subsequent research should also focus on standardizing the criteria of treatment success. Furthermore, no studies directly measured QoL in patients receiving OMNI. Evaluation of QoL is needed to explore the impact of reduced need for medical therapy and other implications of OMNI on patients’ lives.

Conclusion

OMNI demonstrates a favorable safety and efficacy profile and is thus a beneficial treatment option for patients with POAG. Low IOP values are associated with reduced VF progression, and effective treatments should achieve an IOP of ≤18 mmHg. In this SR, meaningful reductions in IOP and medication were observed following treatment with OMNI regardless of baseline IOP. OMNI's duration of effect will help postpone or negate the need for more invasive treatment options, such as bleb-forming surgeries. Limitations of this review and meta-analysis include the absence of RCTs and inability to perform sensitivity analyses because the number of included studies per outcome was limited. Further research is needed to provide longer-term clinical evidence, characterize specific subpopulations, and evaluate the impact of OMNI on humanistic and economic outcomes.