HORIZON: The Data Tells the Story

The HORIZON study was the largest prospective, randomized, controlled MIGS pivotal trial to date.¹

556 Patients
•
38 centers
9 countries

556 Patients
38 centers
9 countries

About the HORIZON Study

A phase 3 clinical trial that compared Hydrus® Microstent plus cataract surgery to cataract surgery alone, split into two phases:

Pivotal stage:

The primary endpoint was the percentage of patients with 20% or greater reduction in diurnal IOP after 2 years of follow-up
Additional monitoring:

Patients were continuously followed for an additional 3 years to monitor safety and to assess predefined efficacy endpoints

Enrolled patients with mild-to-moderate primary open-angle glaucoma on one to four medications.
Patients were randomized 2:1 to Hydrus® Microstent placement (Hydrus + CS; n = 369) or cataract surgery alone (CS alone; n = 187)

HORIZON Met Its Primary Endpoint

The mean reduction in washed-out diurnal IOP at 2 years was -7.5 ±4.1 mm Hg and -5.3 ±3.9 mm Hg in the Hydrus® + CS group and the CS alone group, respectively (difference = -2.2 mm Hg; P < .001)²

The mean number of medications was reduced from 1.7 ±0.9 to 0.3 ±0.8 in the Hydrus® + CS group and from 1.7 ±0.9 to 0.7 ±0.9 in the CS alone group

At 2-years of follow-up, 78% and 48% of eyes were on zero medications in the Hydrus® + CS group and the CS alone group, respectively²

Extended Follow-Up Confirmed Long-Term Efficacy

Five-year follow-up was completed in 80% of patients in the Hydrus® + CS group and in 71.7% in the CS alone group³

The change in IOP versus before surgery was -8.3 ±3.8 mm Hg in the Hydrus® + CS group and -6.5 ±4.0 mm Hg in the CS alone group³

The rate of Secondary Surgical Interventions (SSIs) was lower in the Hydrus® + CS group (2.4%; n = 9/369) compared to the CS alone group (5.3%; n = 10/187)—a greater than 50% relative reduction^3*

*Secondary Surgical Interventions (SSI) include trabeculectomy, tube shunt, gel stent, ECP/TSCP, non-penetrating; (9/369 Hydrus Microstent +cataract surgery and 10/187 cataract surgery); vs. cataract surgery alone: 2.4% in Hydrus + cataract surgery vs. 5.3% in cataract surgery only.

More Profound Effects in Mild Glaucoma

of patients on 1 medication at baseline remained medication-free at 2 years³

Among Hydrus Microstent patients on 1 prior medication, 66.1% remained medication-free for 5 years.

Patients previously on 1 medication: Hydrus Microstent + cataract surgery (n=308 patients) vs. cataract surgery alone (n=134 patients); 41.1% of the cataract surgery-alone patients remained drop-free.

The rate of SSIs among patients on 1 medication at baseline was⁶

in the Hydrus® + CS group

in the CS alone group

Among Hydrus Microstent patients on 1 prior medication, the rate of incisional SSls was 1.8% for Hydrus Microstent + cataract surgery and 4.1% for cataract surgery alone at 5 years.

Excellent Long-Term Safety

Comparable rates of serious adverse events after 5 years of follow-up: 3.5% in the Hydrus® + CS group (n = 13/369) and 4.3% in the CS alone group (n = 8/187)⁵

In the majority of eyes with PAS (30/42 or 71.4%), peripheral anterior synechiae were focal or <1 clock hour in size, there was no adverse impact to IOP or visual acuity, and there were no sequelae observed in eyes with device obstruction

*n=369 eyes receiving Hydrus Microstent + cataract surgery, n=187 eyes receiving cataract surgery alone (results not reported for this endpoint).PAS observation based on gonioscopic appearance, not IOP.

Analysis of Postoperative Endothelial Cell Loss

At 3 months postoperatively, Hydrus^® had an initial postoperative spike in endothelial cell loss versus cataract surgery alone⁵

After this point, the rate of change in endothelial cell density was stable and followed the same trajectory as the cataract surgery only group, with no difference in the rate of postoperative endothelial cell loss⁵

No patients demonstrated any clinically significant sequelae such as corneal edema or corneal decompensation⁵

Post-Hoc Analysis Examined Progressive Visual Field (VF) Damage from 5-Year HORIZON Study⁷

Background

No prospective analysis of VF data was planned in the HORIZON study
A large number of VF assessments were collected over the 5-year study period and used in this analysis
MD worsening ≥2.5 dB at any point was considered an adverse event and was confirmed with 2 additional reliable VF assessments

Methods

All patients had mild-to-moderate POAG, with VF mean deviation (MD) ≥-12 per original inclusion criteria
VF assessments were performed preoperatively and at Months 6, 12, 24, 36, 48, and 60
Included were patients with ≥3 postoperative VF assessments, with the last performed >1 year following surgery
Excluded were preoperative VF assessments (to avoid confounding effects of cataracts) and VF assessments with poor reliability (false-positive error rate >15%)

POAG = primary open angle glaucoma

Endpoints

Primary: Rate of progression of VF damage (dB/year) for Hydrus^® + CS vs. CS alone
Secondary: Cluster and location-specific rates of progression
Included were patients with ≥3 postoperative VF assessments, with the last performed >1 year following surgery

A Bayesian hierarchical censored model (as performed in the LiGHT and TAGS trials) was used to evaluate differences in group, cluster, and pointwise rate of progression

Post-Hoc Analysis Examined Progressive Visual Field (VF) Damage from 5-Year HORIZON Study

Baseline as well as 2-and 5-year global visual field metric data were comparable between groups^2,8*

*n=352 eyes receiving Hydrus Microstent + cataract surgery, n=165 eyes receiving cataract surgery alone.

MD worsening by ≥ 2.5 dB was defined as an adverse event. Safety outcomes were similar between groups.^1,2

Baseline sensitivities (estimated via a separate analysis) were similar between groups after cataract surgery⁷

Approximately 6 VF measurements over 4.9 years were used for each group

The rate of progression was -0.49 dB/year in the CS alone group vs. -0.26 dB/year in the Hydrus® + CS group⁷

Limitations of the post hoc analysis⁷

This type of analysis is limited to use in a research setting due to the complexity of the data and the analysis
Garway-Heath clusters are approximations of the anatomic location of the retinal nerve fibers with likely overlap between clusters
The HORIZON Trial population included mild-to-moderate glaucoma subjects undergoing cataract surgery; these results might not be applicable to subjects with other glaucoma types
Using a hierarchical methodology, The HORIZON 5-year data span identified some visual field progression differences between groups; however, glaucoma is a long-term, unpredictable disease requiring prolonged clinical follow-up
The clinical relevance of these visual field (VF) findings has not been well established
The difference in overall IOP control between groups based on clinic DIOP measurements in HORIZON did not appear to account for the differences in the rates of progression
It is unknown if this presence of “fast progressors” is a result of random chance as this is not something that could be identified in a patient in advance as a part of baseline demographics due to the unpredictability of glaucoma

DIOP=diurnal intraocular pressure; IOP=intraocular pressure.

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

2. 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.

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. Alcon Data on File, 2024. REF-24145.

5. Alcon Data in File, 2021. REF-15037

6. Alcon Data on file, 2023. REF-22437.

7. Montesano G, Ometto G, Ahmed IIK, et al. Five-year visual field outcomes of the HORIZON trial. Am J Ophthalmol. 2023 Jul;251:143-155.

INDICATIONS FOR USE: The Hydrus^® Microstent is intended for the reduction of intraocular pressure (IOP) in patients with primary open angle glaucoma (POAG) as a standalone treatment or in conjunction with cataract surgery.

CONTRAINDICATIONS: The Hydrus^® Microstent is contraindicated under the following circumstances or conditions: (1) In eyes with angle closure glaucoma; (2) In eyes with secondary glaucoma such as neovascular glaucoma or uveitic glaucoma; (3) Patients with known nickel allergy; (4) Pediatric patients less than 18 years of age.

WARNINGS: Clear media for adequate visualization is required. Conditions such as corneal haze, corneal opacity or other conditions may inhibit gonioscopic view of the intended implant location. Gonioscopy should be performed prior to surgery to exclude congenital anomalies of the angle, peripheral anterior synechiae (PAS), angle closure, rubeosis and any other angle abnormalities that could lead to improper placement of the stent and pose a hazard.

PRECAUTIONS: The surgeon should monitor the patient postoperatively for proper maintenance of intraocular pressure. The safety and effectiveness of the Hydrus^® Microstent has not been established as an alternative to the primary treatment of glaucoma with medications, in patients 21 years or younger, eyes with significant prior trauma, eyes with abnormal anterior segment, eyes with chronic inflammation, eyes with glaucoma associated with vascular disorders, eyes with uveitic glaucoma, eyes with other secondary open angle glaucoma, or eyes that have undergone argon laser trabeculoplasty (ALT). The safety and effectiveness of use of more than a single Hydrus^® Microstent or with other metallic implants has not been established.

ADVERSE EVENTS: The most common intra-operative and post-operative device-related ocular adverse events reported include transient hyphema; peripheral anterior synechiae without device obstruction; partial or complete device obstruction; non-persistent anterior uveitis/ iritis; subconjunctival hemorrhage; and device malposition.

MRI INFORMATION: The Hydrus^® Microstent is MR-Conditional meaning that the device is safe for use in a specified MR environment under specified conditions. Please refer to product direction for use for list of indications, contraindications and warnings.