Evaluation of the Safety and Performance of the HARMONI® Toric Lens

Study Overview
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Brief Summary
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The purpose of this study was to evaluate the safety and effectiveness of the HARMONI® Modular Intraocular Lens System with a toric optic (HMTIOL) in subjects with pre-existing corneal astigmatism in need of cataract surgery.

Detailed Description
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Subjects with visually significant bilateral cataracts (cortical, nuclear, posterior subcapsular, or a combination) were implanted unilaterally (in one eye only) or bilaterally (in both eyes) with the HMTIOL. A total of 7 study visits were planned, including a preoperative visit, operative visits for each eye, and 4 follow-up visits at 1 day, 1 week, 1 month, and 3 months postoperative. The total duration of participation for each subject was up to 6 months, including the preoperative period (up to 3 months). Alcon Research, LLC, acquired ClarVista Medical in 2017. This study was designed and conducted by ClarVista Medical, Inc. The study results were collected, analyzed, and provided by ClarVista Medical, Inc. to Alcon Research, LLC.

Official Title
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A Prospective, Multicenter Study to Evaluate the Safety and Performance of the Exchangeable ClarVista HARMONI Modular Toric Intraocular Lens System for the Treatment of Pre-Existing Corneal Astigmatism and Aphakia Following Cataract Surgery

Conditions
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Aphakia, Corneal Astigmatism, Cataract

Intervention / Treatment
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* Device: HARMONI® Modular Toric Intraocular Lens
* Procedure: Cataract extraction with intraocular lens (IOL) implantation


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Planned removal of visually significant bilateral cataract by manual phacoemulsification cataract extraction Pre-existing corneal astigmatism in at least 1 eye of 0.75 to 2.50 diopter (D) Target dioptric lens power within the range of 16 - 26 D Willing to discontinue contact lens wear for the duration of the study BCVA projected to be ≤0.2 logarithm minimum angle of resolution (LogMAR) Stable cornea Dilated pupil size at least 7.0 millimeters (mm) Able to understand and provide informed consent. Key Exclusion Criteria: History of any intraocular or corneal surgery in study eye (including refractive) Pregnant or lactating History of any clinically significant retinal pathology or ocular diagnosis in study eye that could alter or limit final postoperative visual prognosis History of ocular conditions which could affect the stability of the IOL in study eye Any anterior segment pathology likely to increase the risk of complications from phacoemulsification cataract extraction in study eye Any visually significant intraocular media opacity other than cataract in study eye Uncontrolled glaucoma in study eye Uncontrolled systemic disease Severe dry eye that would impair the ability to obtain reliable study measurements Systemic medication that may confound the outcome or increase the intraoperative and postoperative risk to the subject.

Ages Eligible for Study
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Minimum Age: 22 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: HMTIOL<br>HARMONI® Modular Toric Intraocular Lens implanted in the capsular bag following removal of the cataractous lens, intended for lifetime use | Device: HARMONI® Modular Toric Intraocular Lens<br>* Two-component system consisting of a base and a separate toric optic<br>* Other names: HMTIOL;Procedure: Cataract extraction with intraocular lens (IOL) implantation<br>* Cataract removal via manual phacoemulsification, followed by HMTIOL implantation<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean Manifest Refraction Cylinder (MRCYL) for Eyes Implanted With HMTIOL | A manifest refraction (manual vision test) was conducted using letter charts and a phoropter. Manifest refraction cylinder is the amount of added correction needed to compensate for any astigmatism that may be present. MRCYL was measured in diopters and reported as a negative number, with a less negative number indicating a lesser amount of added correction. No formal statistical hypothesis testing was planned. | Month 1 postoperative, Month 3 postoperative | 
| Mean Manifest Refraction Cylinder (MRCYL) Prediction Error (PE) for Eyes Implanted With HMTIOL | A manifest refraction (manual vision test) was conducted using letter charts and a phoropter. Manifest refraction cylinder is the amount of power needed to correct any astigmatism that may be present. MRCYL was measured in diopters and reported as a negative number. MRCYL PE was calculated as postoperative MRCYL adjusted to 6 meters minus MRCYL target residual refractive error (TRRE), with a lower absolute value indicating a more accurate cylinder power calculation. No formal statistical hypothesis testing was planned. | Month 1 postoperative, Month 3 postoperative | 
| MRCYL PE for Eyes Implanted With HMTIOL Per Vector Analyses | Manifest refraction cylinder is the amount of power needed to correct any astigmatism that may be present. MRCYL PE is calculated as postoperative MRCYL adjusted to 6 meters minus MRCYL target residual refractive error (TRRE), with a lower absolute value indicating a more accurate cylinder power calculation. No formal statistical hypothesis testing was planned. | Month 1 postoperative, Month 3 postoperative | 
| Mean Reduction in Cylinder Power for Eyes Implanted With HMTIOL | A manifest refraction (manual vision test) was conducted using letter charts and a phoropter. Manifest refraction cylinder is the amount of power needed to correct any astigmatism that may be present. MRCYL was measured in diopters and reported as a negative number. Cylinder power reduction was calculated as the absolute preoperative magnitude of corneal cylinder (K) minus the absolute postoperative magnitude of MRCYL at the corneal plane. No formal statistical hypothesis testing was planned. | Baseline (Day 0 preoperative), Month 3 postoperative | 
| Mean Percent Reduction in Cylinder Power for Eyes Implanted With HMTIOL | A manifest refraction (manual vision test) was conducted using letter charts and a phoropter. Manifest refraction cylinder is the amount of power needed to correct any astigmatism that may be present. MRCYL was measured in diopters and reported as a negative number. Cylinder power reduction was calculated as the absolute preoperative magnitude of corneal cylinder (K) minus the absolute postoperative magnitude of MRCYL at the corneal plane. Therefore, the cylindrical power percent reduction was the cylinder power reduction divided by the absolute value of preoperative magnitude of corneal cylinder (K) × 100. A higher number (greater percent reduction) indicates better astigmatism correction by the toric IOL. No formal statistical hypothesis testing was planned. | Baseline (Day 0 preoperative), Month 3 postoperative | 
| Mean Manifest Refraction Spherical Equivalent (MRSE) Prediction Error (PE) | A manifest refraction (manual vision test) was conducted using letter charts and a phoropter. The manifest refraction spherical equivalent (MRSE) was calculated as follows: sphere + 1/2 cylinder, and measured in diopters (D). MRSE PE was calculated as postoperative MRSE adjusted to 6 meters minus MRSE target residual refractive error (TRRE). The lower the absolute number, the more accurate the IOL power calculation is. No formal statistical hypothesis testing was planned. | Month 1 postoperative, Month 3 postoperative | 
| Mean Absolute Misalignment of IOL Meridian - Target Versus Actual at Operative Visit | Absolute misalignment of IOL meridian was defined as the summation of IOL misplacement and IOL rotation. A lower number indicates minimal IOL misalignment. No formal statistical hypothesis testing was planned. | Day 0 (operative) | 
| Mean Absolute Rotation of IOL Meridian by Visit | IOL orientation was measured with slit-lamp photography. IOL rotation was defined as the difference between axis of IOL orientation on the day of surgery and the subsequent postoperative visit. IOL rotation was measured in degrees. No formal statistical hypothesis testing was planned. | Baseline (Day 0 preoperative), Day 1 postoperative, Week 1 postoperative, Month 1 postoperative, Month 3 postoperative | 
| Number of Eyes With Absolute Rotation of IOL Meridian by Visit | IOL orientation was measured with slit-lamp photography. IOL rotation was defined as the difference between axis of IOL orientation on the day of surgery and the subsequent postoperative visit. IOL rotation was measured in degrees and is reported categorically. No formal statistical hypothesis testing was planned. | Baseline (Day 0 preoperative), Day 1 postoperative, Week 1 postoperative, Month 1 postoperative, Month 3 postoperative | 
| Percentage of Eyes With Best Corrected Distance Visual Acuity (BCDVA) by Visit | Visual Acuity of the eye was tested while reading charts at 20-foot equivalent distance from the participant with the correction obtained from manifest refraction testing. BCDVA is reported categorically using the Snellen fraction, which compares the participant's result to the result expected from a 'normal' visual system. The numerator represents the distance between the participant and the chart, and the denominator represents the distance at which a person with 'normal' vision would be able to discern the same letter size. 20/20 is considered to be 'normal' vision, whereas visual acuity of 20/40 means the participant is able to read a certain size letter 20 feet away that a person with 'normal' vision would be able to read from 40 feet away. A larger denominator, therefore, indicates a lower visual acuity. No formal statistical hypothesis testing was planned. | Baseline (Day 0 preoperative), Week 1 postoperative, Month 1 postoperative, Month 3 postoperative | 
| Percentage of Eyes With Uncorrected Distance Visual Acuity (UCDVA) by Visit | Visual Acuity of the eye was tested while reading charts at 20-foot equivalent distance from the participant with an optical infinity adjustment of +0.25 diopter (D). UCDVA is reported categorically using the Snellen fraction, which compares the participant's result to the result expected from a 'normal' visual system. The numerator represents the distance between the participant and the chart, and the denominator represents the distance at which a person with 'normal' vision would be able to discern the same letter size. 20/20 is considered to be 'normal' vision, whereas visual acuity of 20/40 means the participant is able to read a certain size letter 20 feet away that a person with 'normal' vision would be able to read from 40 feet away. A larger denominator, therefore, indicates a lower visual acuity. No formal statistical hypothesis testing was planned. | Baseline (Day 0 preoperative), Day 1 postoperative, Week 1 postoperative, Month 1 postoperative, Month 3 postoperative | 
| Standard Error of the Mean in Lens Power A-constant for Refinement | The A-constant (lens power constant) is a theoretical value that is used to calculate the power of the intraocular lens. It relates the lens power to the eye's axial length and keratometry. It is not expressed in units; it is specific to the design of the IOL and its intended location and orientation within the eye. A-constants are typically empirically developed for new IOLs based on hundreds of clinical uses. Data from a sufficient number of eyes are needed in order to reduce bias due to surgical technique, unusual eyes, and differences in equipment, such that the standard error of the mean in the lens power constant would be less than ±0.10 mm (approximately ±0.2 diopter). This study represented the first clinical use of the HMTIOL. | Day 0 operative | 
| Number of Ocular Adverse Events Through Month 3 | Ocular adverse events were identified as outlined in ISO 11979-2014 Annex B. No formal statistical hypothesis testing was planned. | Up to Month 3 postoperative | 
| Number of Device-Related Secondary Surgical Interventions (SSI) Other Than Optic Exchange and Rotational Adjustment of the HMTIOL | A secondary surgical intervention (SSI) was defined as a surgical procedure that occurred after primary implantation and was conducted for the purpose of resolving residual refractive error (RRE) and optimizing visual outcomes. No formal statistical hypothesis testing was planned. | Up to Month 3 postoperative | 
| Number of Device Deficiencies Post Implantation | A device deficiency was defined as a failure of the device to meet its performance specifications or expectations, or otherwise not perform as intended. This could include either a malfunction or damage to the device or any part thereof, regardless of the source of malfunction or damage, including user error, and regardless of the presence of injury (or lack thereof) to subject, user, or bystander. No formal statistical hypothesis testing was planned. | Up to Month 3 postoperative | 
| Number of Eyes With Preservation of Best Corrected Distance Visual Acuity (BCDVA) at Month 1 and Month 3 | Preservation of BCDVA was defined in terms of lines lost when reading the ETDRS chart at each visit compared to the prior best-achieved BCDVA. Loss of < 1 line included subjects with less than a 1 line loss, no change or improvement in BCDVA. No formal statistical hypothesis testing was planned. | Month 1 postoperative, Month 3 postoperative | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Toric, Intraocular lens