ClarVista HARMONI Toric Trial With Intraoperative Exchange

Subjects were implanted with the HARMONI® Modular Intraocular Lens System (HMIOL). The eye with the higher corneal astigmatism (study eye) was assigned to Cohort 1 and received the HARMONI® Modular Intraocular Lens System with a toric optic. The fellow eye was assigned to Cohort 2 and received the HARMONI® Modular Intraocular Lens System with a non-toric optic during primary implantation, which was replaced with the appropriate optic power (toric or non-toric) during an intraoperative exchange (IOE) procedure. 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, which included a Day -90 to Day -0 preoperative period.

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.

• HARMONI® Modular Intraocular Lens System (Device), also known as HMIOL: Two-component system consisting of a base and a separate optic that allows for an intraoperative exchange of the optic only without direct manipulation of the capsular bag
• Intraoperative optic exchange (Procedure), also known as IOE: Removal of one optic and replacement with another during cataract surgery for the purpose of improving refractive outcomes

Primary outcomes

• Mean Manifest Refraction Cylinder (MRCYL) for Eyes Implanted With HMTIOL [Month 1 postoperative, Month 3 postoperative]: 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.
• Mean Manifest Refraction Cylinder (MRCYL) Prediction Error (PE) for Eyes Implanted With HMTIOL [Month 1 postoperative, Month 3 postoperative]: 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.
• Mean Reduction in Cylinder Power for Eyes Implanted With HMTIOL [Baseline (Day 0 preoperative), Month 3 postoperative]: 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.
• Mean Percent Reduction in Cylinder Power for Eyes Implanted With HMTIOL [Baseline (Day 0 preoperative), Month 3 postoperative]: 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.
• Mean Manifest Refraction Spherical Equivalent (MRSE) Prediction Error (PE) [Month 3 postoperative]: 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.
• Mean Absolute Rotation of IOL Meridian [Baseline (Day 0 operative), Day 1 postoperative, Week 1 postoperative, Month 1 postoperative, Month 3 postoperative]: 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, with a lower number indicating less rotation. No formal statistical hypothesis testing was planned.
• Number of Eyes With Absolute Rotation of IOL Meridian by Visit - Cohort 1 [Baseline (Day 0 operative), Day 1 postoperative, Week 1 postoperative, Month 1 postoperative, Month 3 postoperative]: 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.
• Number of Eyes With Absolute Rotation of IOL Meridian by Visit - Cohort 2 [Baseline (Day 0 operative), Day 1 postoperative, Week 1 postoperative, Month 1 postoperative, Month 3 postoperative]: 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.
• Percentage of Eyes With Best Corrected Distance Visual Acuity (BCDVA) by Visit - Cohort 1 [Baseline (Day 0 operative), Week 1 postoperative, Month 1 postoperative, Month 3 postoperative]: 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.
• Percentage of Eyes With Best Corrected Distance Visual Acuity (BCDVA) by Visit - Cohort 2 [Baseline (Day 0 operative), Week 1 postoperative, Month 1 postoperative, Month 3 postoperative]: 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. 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.
• Percentage of Eyes With Uncorrected Distance Visual Acuity (UCDVA) by Visit - Cohort 1 [Baseline (Day 0 operative), Day 1 postoperative, Week 1 postoperative, Month 1 postoperative, Month 3 postoperative]: 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). The Snellen fraction 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.
• Percentage of Eyes With Uncorrected Distance Visual Acuity (UCDVA) by Visit - Cohort 2 [Baseline (Day 0 operative), Day 1 postoperative, Week 1 postoperative, Month 1 postoperative, Month 3 postoperative]: 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). The Snellen fraction 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.
• Number of Eyes With Preservation of BCDVA at Month 1 and Month 3 [Week 1 postoperative, Month 1 postoperative, Month 3 postoperative]: 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.
• Number of Ocular Adverse Events Through Month 3 [Up to Month 3 postoperative]: Ocular adverse events were identified as outlined in ISO 11979-2014 Annex B. No formal statistical hypothesis testing was planned.
• Number of Device Deficiencies Post Implantation [Up to Month 3 postoperative]: A Device Deficiency (DD) 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.
• Number of Secondary Surgical Interventions, Other Than Intraroperative Optic Exchange and Rotational Adjustment of the Toric Optic in Cohort 2 [Up to Month 3 postoperative]: 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.
• Percent Change in Endothelial Cell Count (ECC) at Month 3 [Baseline (preoperative), Month 3 postoperative]: High quality images of the corneal endothelium (the single layer of cells on the inner surface of the cornea) were taken at the investigative site and sent to an independent central reading center for evaluation. A negative percent change value may indicate a decrease in the ability of the endothelium to maintain its primary function. No formal statistical hypothesis testing was planned.

Sex: All, ages: 22 Years to any

Key Inclusion Criteria

* Willing and able to return for scheduled treatment and follow-up examinations for up to 6 month study duration.
* Planned removal of visually significant bilateral cataracts.
* Pre-existing corneal astigmatism in at least 1 eye.
* Willing to discontinue contact lens wear for the duration of the study.
* Best Corrected Visual Acuity (BCVA) projected to be 0.2 logarithm Minimum Angle of Resolution (logMAR) or lower.
* Visual symptoms related to cataracts.

Key Exclusion Criteria

* History of any intraocular or corneal surgery in either eye (including refractive).
* Pregnant or lactating.
* History of any clinically significant retinal pathology or ocular diagnosis in either eye that could alter or limit final postoperative visual prognosis.
* History of any ocular condition which could affect the stability of the intraocular lens (IOL) in either eye.
* Uncontrolled glaucoma in either eye (per Investigator judgement).
* Severe dry eye that, in the opinion of the investigator, would impair the ability to obtain reliable study measurements

Participant flow

Outcome results

• Mean Manifest Refraction Cylinder (MRCYL) for Eyes Implanted With HMTIOL (Primary), Mean, diopter: Cohort 1 -0.54 +/- 0.32; Cohort 2 -0.75 +/- 0.31
• Mean Manifest Refraction Cylinder (MRCYL) Prediction Error (PE) for Eyes Implanted With HMTIOL (Primary), Mean, diopter: Cohort 1 -0.30 +/- 0.28; Cohort 2 -0.53 +/- 0.36
• Mean Reduction in Cylinder Power for Eyes Implanted With HMTIOL (Primary), Mean, diopter: Cohort 1 0.79 +/- 0.56; Cohort 2 0.53 +/- 0.39
• Mean Percent Reduction in Cylinder Power for Eyes Implanted With HMTIOL (Primary), Mean, percent reduction: Cohort 1 54.9 +/- 29.3; Cohort 2 39.5 +/- 34.2
• Mean Manifest Refraction Spherical Equivalent (MRSE) Prediction Error (PE) (Primary), Mean, diopter: Cohort 1 0.03 +/- 0.45; Cohort 2 -0.12 +/- 0.43
• Mean Absolute Rotation of IOL Meridian (Primary), Mean, degrees: Cohort 1 1.8 +/- 1.3; Cohort 2 2.1 +/- 1.4
• Number of Eyes With Absolute Rotation of IOL Meridian by Visit - Cohort 1 (Primary), Number, eyes: Cohort 1 - Day 1 Postoperative 22; Cohort 1 - Week 1 Postoperative 23; Cohort 1 - Month 1 Postoperative 23; Cohort 1 - Month 3 Postoperative 22
• Number of Eyes With Absolute Rotation of IOL Meridian by Visit - Cohort 2 (Primary), Number, eyes: Cohort 2 - Day 1 Postoperative 20; Cohort 2 - Week 1 Postoperative 17; Cohort 2 - Month 1 Postoperative 18; Cohort 2 - Month 3 Postoperative 19
• Percentage of Eyes With Best Corrected Distance Visual Acuity (BCDVA) by Visit - Cohort 1 (Primary), Number, Percentage of eyes: Cohort 1 - Baseline (Day 0 Preoperative) 22.2; Cohort 1 - Week 1 Postoperative 66.7; Cohort 1 - Month 1 Postoperative 59.3; Cohort 1 - Month 3 Postoperative 70.4
• Percentage of Eyes With Best Corrected Distance Visual Acuity (BCDVA) by Visit - Cohort 2 (Primary), Number, percentage of eyes: Cohort 2 - Baseline (Day 0 Preoperative) 23.1; Cohort 2 - Week 1 Postoperative 76.9; Cohort 2 - Month 1 Postoperative 73.1; Cohort 2 - Month 3 Postoperative 76.9
• Percentage of Eyes With Uncorrected Distance Visual Acuity (UCDVA) by Visit - Cohort 1 (Primary), Number, percentage of eyes: Cohort 1 - Baseline (Day 0 Preoperative) 3.7; Day 1 Postoperative 48.1; Cohort 1 - Week 1 Postoperative 44.4; Cohort 1 - Month 1 Postoperative 40.7; Cohort 1 - Month 3 Postoperative 40.7
• Percentage of Eyes With Uncorrected Distance Visual Acuity (UCDVA) by Visit - Cohort 2 (Primary), Number, percentage of eyes: Cohort 2 - Baseline (Day 0 Preoperative) 0.0; Cohort 2 - Day 1 Postoperative 46.2; Cohort 2 - Week 1 Postoperative 53.8; Cohort 2 - Month 1 Postoperative 42.3; Cohort 2 - Month 3 Postoperative 34.6
• Number of Eyes With Preservation of BCDVA at Month 1 and Month 3 (Primary), Number, eyes: Cohort 1 - Month 1 Postoperative 27; Cohort 1 - Month 3 Postoperative 25; Cohort 2 - Month 1 Postoperative 25; Cohort 2 - Month 3 Postoperative 26
• Number of Ocular Adverse Events Through Month 3 (Primary), Number, adverse event: Cohort 1 1; Cohort 2 0
• Number of Device Deficiencies Post Implantation (Primary), Number, device deficiency: Cohort 1 - No Exchange 0; Cohort 2 - Intraoperative Exchange 0
• Number of Secondary Surgical Interventions, Other Than Intraroperative Optic Exchange and Rotational Adjustment of the Toric Optic in Cohort 2 (Primary), Number, Secondary surgical interventions: Cohort 1 - No Exchange 0; Cohort 2 - Intraoperative Exchange 0
• Percent Change in Endothelial Cell Count (ECC) at Month 3 (Primary), Mean, percent change: Cohort 1 - No Exchange -12.5 +/- 10.1; Cohort 2 - Intraoperative Exchange -9.0 +/- 10.3

Adverse events

Time frame: Adverse events were collected from time of consent until study exit: Up to 6 months, including a Day -90 to Day -0 preoperative period and a 3-month postoperative period.

Serious adverse events by term

• Study Protocol (PDF, 2016-12-01)
• Statistical Analysis Plan (PDF, 2017-08-14)

• Sr. Clinical Trial Lead, CDMA Surgical, Study director, Alcon Research, LLC