Background

The HORIZON trial was a phase 3 clinical trial conducted in two phases.¹ The first portion was designed as a 2-year pivotal study comparing Hydrus Microstent (Alcon LLC; Fort Worth, TX; USA) plus cataract surgery (CS) to CS alone. In the second phase, patients were studied for an additional 3 years for ongoing safety monitoring, as well as assessment of predefined efficacy endpoints. At a topline, the study met its primary endpoint: a statistically greater percentage of patients in the Hydrus plus CS group had 20% or greater reduction in washed-out diurnal IOP (DIOP) compared to the CS group; the secondary endpoint, change in washed-out DIOP, also favored the Hydrus plus CS group. Serious adverse events were similar between the two groups. Efficacy outcomes were confirmed after 5 years of follow-up, with a number of secondary endpoints showing significant and clinically meaningful benefits.

Key Facts, Demographics, and Enrollment^1,2

• HORIZON is the largest of the micro-invasive glaucoma surgery (MIGS) pivotal trials conducted to date, with 38 sites in nine countries. Approximately 40% of the Hydrus patient population came from outside the United States.

• Groups were matched for baseline demographics.
• Approximately 80% of enrollment was retained at 5 years.

• The study included subjects with mild to moderate primary open-angle glaucoma on one to four glaucoma medications.
• The subjects underwent CS and were randomized 2:1 to include either device placement (n = 369) or CS alone (n = 187).
• IOP and medication count, as well as safety, were assessed at months 1, 3, 6, 12, 18, and 24 postoperatively.

Two-Year Findings

Efficacy

• Primary endpoint (Figure 1).
• The difference in medication-free eyes throughout follow-up may reflect the clinical effect of device implantation (Figure 2).

Safety

• There was a low percentage of adverse events, overall.
• The rate of peripheral anterior synechiae (PAS) was greater in the Hydrus arm, but most were nonobstructive and did not affect the outcome.

Five-Year Data³

Safety

• Primary safety outcomes:

• There were no sight threatening adverse events related to the Hydrus Microstent.
• The percent of subjects with reported serious adverse events was 3.5% in the Hydrus plus CS group (n = 13/369) and 4.3% in CS alone group (n = 8/187).

• Secondary safety outcomes:

• No significant difference in safety outcomes from 2 to 5 years except for PAS:

• PAS was significantly higher at 5 years for Hydrus Microstent: 14.6% versus 3.7% (P = .0001).
• The majority of Hydrus Microstent eyes with PAS (8.7%) were not device obstructing.
• No difference in IOP control between Hydrus patients with and without PAS: 16.9± 3.3 mmHg versus 16.6± 3.5 mmHg (P = .49).

• The baseline mean central endothelial cell density (ECD) was comparable between groups (P = .81).

• The between-group difference in mean central ECD was 2% at 3 months (11% CS, 13% Hydrus) which increased to 6% over 5 years (13% CS, 19% Hydrus), which was not significant.
• The 3-month postoperative decrease may be attributable to the additional manipulation when inserting the Hydrus Microstent (Figure 3).
• At 3 months, ≥ 30% endothelial cell loss (ECL) occurred in 17.3% in the Hydrus group and 9.4% in the CS group (difference = 7.9%).
• At the 5-year follow up, the proportion with ≥ 30% ECL increased from 17.3% at 3 months to 20.8% (P = .27) in the Hydrus group and from 9.4% at 3 months to 10.6% (P = .85) in the CS group.
• Logistic regression showed no difference in the rate of change of ≥ 30% ECL between the Hyrdus group compared to the CS group from 3 months to 5 years (P = .82).
• No eyes with ≥ 30% ECL in Hydrus Microstent or CS groups had associated clinical sequelae.

Secondary Effectiveness Outcomes⁴

• There was a > 50% reduction in the rate of secondary IOP lowering interventions with Hydrus plus CS versus CS alone (2.4% versus 5.3%).

• The lower cumulative rate of secondary procedures (inclusive of nonincisional procedures) with Hydrus plus CS versus CS alone was 4.9% versus 7.5%.

• The change in diurnal IOP versus before surgery (mm Hg) in unmedicated patients was mean ± SD: -8.0 ± 3.6 in the Hydrus plus CS group versus -6.5 ± 3.5 in the CS group.⁵
• Medication-free eyes were 59% in the Hydrus plus CS group versus 36% in the CS group.⁵

• Medication-free eyes with a ≥ 20% IOP reduction were 48.4% in the Hydrus plus CS group versus 25.4% in the CS group.⁵

1. Samuelson TW, Chang DF, Marquis R, et al; HORIZON Investigators. A schlemm canal microstent for intraocular pressure reduction in primary open-angle glaucoma and cataract: The HORIZON Study. Ophthalmology. 2019;126(1):29-37.

2. Ahmed IIK, Rhee DJ, Jones J, et al; HORIZON Investigators. Three-year findings of the HORIZON Trial: a schlemm canal microstent for pressure reduction in primary open-angle glaucoma and cataract. Ophthalmology. 2021;128(6):857-865.

3. Ahmed IIK, De Francesco T, Rhee D, et al; HORIZON Investigators. Long-term outcomes from the HORIZON Randomized Trial for a schlemm’s canal microstent in combination cataract and glaucoma surgery. Ophthalmology. 2022;129(7):742-751.

4. HYDRUS Microstent [instructions for use]. Irvine, CA: Alcon Vision LLC; September 2021 (United States).

5. Alcon data on file, 2024.