A Clinical Investigation of the ClarVista HARMONI™ Modular Intraocular Lens Implant Following Cataract Surgery

• Sponsor: ClarVista Medical (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02521766
• Collaborator: (none)
• Enrollment: 217
• Locations: 2
• Arms: 4
• Actual Duration (Months): 24.8
• Patients Per Site: 108.5
• Patients Per Site Per Month: 4.4

Study Details

Study Description

Brief Summary

The main objectives of this feasibility study were:

• To demonstrate the feasibility of HARMONI Modular Intraocular Lens (HMIOL) implantation and assembly in subjects undergoing cataract surgery (All HMIOL Cohort), and

• To demonstrate the feasibility of the HMIOL optic component exchange procedure (performed 3 months following primary cataract extraction) (Cohort 2).

Condition or Disease	Intervention/Treatment	Phase
Cataract	Device: Harmoni Modular Intraocular Lens; Device: Commercially Available Intraocular Lens; Procedure: Optic exchange	N/A

Detailed Description

Eligible subjects with bilateral cataracts underwent cataract extraction and IOL implantation using phacoemulsification. The study eye was implanted with the investigational device (All HMIOL Cohort). The fellow eye was treated with a commercially available intraocular lens (IOL) per standard of care procedure. At the scheduled Month 3 post-operative visit, subjects who did not opt to pursue an optic exchange procedure in the study eye were enrolled into subgroup Cohort 1 and followed for an additional 6 months. The total duration of participation for Cohort 1 was up to 15 months, which included a Day -90 to Day -1 preoperative period and a 12 month post-operative follow-up period. At the scheduled Month 3 post-operative visit, subjects who elected to pursue an optic exchange procedure in the study eye were enrolled into subgroup Cohort 2 and followed for an additional 12 months. The total duration of participation for Cohort 2 was up to 18 months, which included a Day -90 to Day -1 preoperative period, an optic exchange at Month 3 postoperative, and a 12 month post-exchange follow-up period.

Alcon Research, LLC, acquired ClarVista Medical in 2017. This study was designed and conducted by ClarVista Medical, Inc., to evaluate the safety and effectiveness of the HMIOL. The study results were collected, analyzed, and provided by ClarVista Medical, Inc. to Alcon Research, LLC.

Study Design

• Study Type: Interventional
• Actual Enrollment: 217 participants
• Allocation: Non-Randomized
• Intervention Model: Single Group Assignment
• Masking: Single (Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Prospective, Multi-Center, Feasibility Trial of the ClarVista HARMONI™ Modular Intraocular Lens System for the Treatment of Aphakia Following Cataract Surgery
• Actual Study Start Date: Oct 1, 2015
• Actual Primary Completion Date: Feb 7, 2017
• Actual Study Completion Date: Oct 26, 2017

Arms and Interventions

Arm	Intervention/Treatment
Experimental: All HMIOL Cohort HMIOL implantation with or without optic exchange	Device: Harmoni Modular Intraocular Lens; 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; Other Names: HMIOL
Experimental: Cohort 1 HMIOL implantation with no optic exchange	Device: Harmoni Modular Intraocular Lens; 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; Other Names: HMIOL
Experimental: Cohort 2 HMIOL implantation with optic exchange	Device: Harmoni Modular Intraocular Lens; 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; Other Names: HMIOL ; Procedure: Optic exchange; Removal of one optic and replacement with another for the purpose of improving refractive outcomes
Other: Fellow Eye IOL implantation per standard of care	Device: Commercially Available Intraocular Lens; IOL per investigator's standard of care

Outcome Measures

Primary Outcome Measures

1. Percentage of Eyes With Postoperative BCDVA 20/40 Snellen or Better by Study Visit - All HMIOL Cohort [Month 1 postoperative, Month 3 postoperative]

   Visual acuity (VA) was assessed using the Early Treatment Diabetic Retinopathy Study (ETDRS)-Fast method under well-lit conditions at a distance of 4 meters (m) with the correction obtained from manifest refraction testing. BCDVA was recorded in Snellen, with 20/20 considered to be 'normal' vision. A 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. This analysis was prespecified for the study eye. No formal statistical hypothesis testing was planned.

2. Percentage of Eyes With Postoperative BCDVA 20/40 Snellen or Better by Study Visit - Cohort 1 [Month 1 postoperative, Month 3 postoperative, Month 6 postoperative, Month 12 postoperative]

   VA was assessed using the ETDRS-Fast method under well-lit conditions at a distance of 4 m with the correction obtained from manifest refraction testing. BCDVA was recorded in Snellen, with 20/20 considered to be 'normal' vision. A 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. This analysis was prespecified for the study eye. No formal statistical hypothesis testing was planned.

3. Percentage of Eyes With Postoperative BCDVA 20/40 Snellen or Better by Study Visit - Cohort 2 [Month 1 postoperative, Month 3 postoperative, Week 1 post-optic exchange, Month 1 post-optic exchange, Month 3 post-optic exchange, Month 6 post-optic exchange, Month 12 post-optic exchange]

   VA was assessed using the ETDRS-Fast method under well-lit conditions at a distance of 4 m with the correction obtained from manifest refraction testing. BCDVA was recorded in Snellen, with 20/20 considered to be 'normal' vision. A 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. An optic exchange occurred at the Month 3 visit, after which subjects were followed for an additional 12 months. Month 1 postoperative and Month 3 postoperative visits were pre-optic exchange. This analysis was prespecified for the study eye. No formal statistical hypothesis testing was planned

4. Percentage of Eyes With Postoperative BCDVA 20/40 Snellen or Better by Study Visit - Fellow Eye [Month 1 postoperative, Month 3 postoperative, Month 12 postoperative]

   VA was assessed using the ETDRS-Fast method under well-lit conditions at a distance of 4 m with the correction obtained from manifest refraction testing. BCDVA was recorded in Snellen, with 20/20 considered to be 'normal' vision. A 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. This analysis was prespecified for the study eye. No formal statistical hypothesis testing was planned.

5. Percentage of Eyes With Postoperative Manifest Refraction Spherical Equivalent (MRSE) Within Target by Study Visit - All HMIOL Cohort [Week 1 postoperative, Month 1 postoperative, 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). This analysis was prespecified for the study eye. No formal statistical hypothesis testing was planned.

6. Percentage of Eyes With Postoperative Manifest Refraction Spherical Equivalent (MRSE) Within Target by Study Visit - Cohort 1 [Week 1 postoperative, Month 1 postoperative, Month 3 postoperative, Month 6 postoperative, Month 12 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). This analysis was prespecified for the study eye. No formal statistical hypothesis testing was planned.

7. Percentage of Eyes With Postoperative Manifest Refraction Spherical Equivalent (MRSE) Within Target by Study Visit - Cohort 2 [Week 1 postoperative, Month 1 postoperative, Month 3 postoperative, Week 1 post-optic exchange, Month 1 post-optic exchange, Month 3 post-optic exchange, Month 6 post-optic exchange, Month 12 post-optic exchange]

   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). An optic exchange occurred at the Month 3 visit, after which subjects were followed for an additional 12 months. Week 1 postoperative, Month 1 postoperative, and Month 3 postoperative visits were pre-optic exchange. This analysis was prespecified for the study eye. No formal statistical hypothesis testing was planned.

8. Percentage of Eyes With Postoperative Manifest Refraction Spherical Equivalent (MRSE) Within Target by Study Visit - Fellow Eye [Month 1 postoperative, Month 3 postoperative, Month 12 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). This analysis was prespecified for the fellow eye. No formal statistical hypothesis testing was planned.

9. Mean BCDVA (Letters Read) by Study Visit - All HMIOL Cohort [Day -90 to Day -1 preoperative, Month 1 postoperative, Month 3 postoperative]

   VA was assessed using the ETDRS-Fast method under well-lit conditions at a distance of 4 m with the correction obtained from manifest refraction testing. BCDVA was recorded in letters read correctly. This analysis was prespecified for the study eye. No formal statistical hypothesis testing was planned.

10. Mean BCDVA (Letters Read) by Study Visit - Cohort 1 [Day -90 to -1 preoperative, Month 1 postoperative, Month 3 postoperative, Month 6 postoperative, Month 12 postoperative]

    VA was assessed using the ETDRS-Fast method under well-lit conditions at a distance of 4 m with the correction obtained from manifest refraction testing. BCDVA was recorded in letters read correctly. This analysis was prespecified for the study eye. No formal statistical hypothesis testing was planned.

11. Mean BCDVA (Letters Read) by Study Visit - Cohort 2 [Day -90 to -1 preoperative, Month 1 postoperative, Month 3 postoperative, Week 1 post-optic exchange, Month 1 post-optic exchange, Month 3 post-optic exchange, Month 6 post-optic exchange, Month 12 post-optic exchange]

    VA was assessed using the ETDRS-Fast method under well-lit conditions at a distance of 4 m with the correction obtained from manifest refraction testing. BCDVA was recorded in letters read correctly. An optic exchange occurred at the Month 3 visit, after which subjects were followed for an additional 12 months. Month 1 postoperative and Month 3 postoperative visits were pre-optic exchange.This analysis was prespecified for the study eye. No formal statistical hypothesis testing was planned.

12. Mean BCDVA (Letters Read) by Study Visit - Fellow Eye [Day -90 to -1 preoperative, Month 1 postoperative, Month 3 postoperative, Month 12 postoperative]

    VA was assessed using the ETDRS-Fast method under well-lit conditions at a distance of 4 m with the correction obtained from manifest refraction testing. BCDVA was rrecorded in letters read correctly. This analysis was prespecified for the fellow eye. No formal statistical hypothesis testing was planned.

13. Mean Uncorrected Distance Visual Acuity (UCDVA) (Letters Read) by Study Visit - All HMIOL Cohort [Day 1 postoperative, Week 1 postoperative, Month 1 postoperative, Month 3 postoperative]

    VA was assessed using the ETDRS-Fast method under well-lit conditions at a distance of 4 m with an optical infinity adjustment of +0.25 diopter (D). UCDVA was recorded in letters read correctly. This analysis was prespecified for the study eye. No formal statistical hypothesis testing was planned.

14. Mean Uncorrected Distance Visual Acuity (UCDVA) (Letters Read) by Study Visit - Cohort 1 [Day 1 postoperative, Week 1 postoperative, Month 1 postoperative, Month 3 postoperative, Month 6 postoperative, Month 12 postoperative]

    VA was assessed using the ETDRS-Fast method under well-lit conditions at a distance of 4 m with an optical infinity adjustment of +0.25 diopter (D). UCDVA was recorded in letters read correctly. This analysis was prespecified for the study eye. No formal statistical hypothesis testing was planned.

15. Mean Uncorrected Distance Visual Acuity (UCDVA) (Letters Read) by Study Visit - Cohort 2 [Day 1 postoperative, Week 1 postoperative, Month 1 postoperative, Month 3 postoperative, Day 1 post-optic exchange, Week 1 post-optic exchange, Month 1 post-optic exchange, Month 3 post-optic exchange, Month 6 post-optic exchange, Month 12 post-optic exch]

    VA was assessed using the ETDRS-Fast method under well-lit conditions at a distance of 4 m with an optical infinity adjustment of +0.25 diopter (D). UCDVA was recorded in letters read correctly. An optic exchange occurred at the Month 3 visit, after which subjects were followed for an additional 12 months. Day 1 postoperative, Week 1 postoperative, Month 1 postoperative, and Month 3 postoperative visits were pre-optic exchange. This analysis was prespecified for the study eye. No formal statistical hypothesis testing was planned.

16. Mean Uncorrected Distance Visual Acuity (UCDVA) (Letters Read) by Study Visit - Fellow Eye [Day 1 postoperative, Week 1 postoperative, Month 1 postoperative, Month 3 postoperative, Month 6 postoperative, Month 12 postoperative]

    VA was assessed using the ETDRS-Fast method under well-lit conditions at a distance of 4 m with an optical infinity adjustment of +0.25 diopter (D). UCDVA was recorded in letters read correctly. This analysis was prespecified for the fellow eye. No formal statistical hypothesis testing was planned.

17. Percentage of Eyes With UCDVA by Category (Snellen) for Each Post-optic Exchange Study Visit - Cohort 2 [Day 1 post-optic exchange, Week 1 post-optic exchange, Month 1 post-optic exchange, Month 3 post-optic exchange, Month 6 post-optic exchange, Month 12 post-optic exchange]

    VA was assessed using the ETDRS-Fast method under well-lit conditions at a distance of 4 m with an optical infinity adjustment of +0.25 diopter (D). UCDVA was recorded in Snellen, with 20/20 considered to be 'normal' vision. A 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. An optic exchange occurred at the Month 3 visit, after which subjects were followed for an additional 12 months. Day 1 postoperative, Week 1 postoperative, Month 1 postoperative, and Month 3 postoperative visits were pre-optic exchange. This analysis was prespecified for the study eye, Cohort 2 only. No formal statistical hypothesis testing was planned.

18. Mesopic Best Corrected Distance Visual Acuity (mBCDVA) (With and Without Glare) (Letters Read) at Study Visit - All HMIOL Cohort [Month 3 postoperative]

    VA was assessed using the ETDRS-Fast method under mesopic (dimly lit) conditions at a distance of 4 m with the correction obtained from manifest refraction testing. Testing was performed with and without glare. Chart luminance was set to 3 cd/m2. mBCDVA was recorded in letters read correctly. This analysis was prespecified for the study eye, All HMIOL Cohort only. No formal statistical hypothesis testing was planned.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 22 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Must be able to understand and provide informed consent

• Must be willing and able to return for scheduled treatment and follow-up examinations for up to 15 month study duration

• Planned bilateral removal of visually significant bilateral cataracts

• Best-corrected distance visual acuity (BCDVA) projected to be better than 20/32 after IOL implantation in both eyes

• Preoperative bilateral BCDVA of 20/40 or worse

• Both eyes must have corneal astigmatism ≤ 1.50 diopter (D)

• Women must be post-menopausal ≥1 year or surgically sterilized, or a pregnancy screen must be performed prior to the study and a reliable form of contraception, approved by the investigator, must be maintained during the study

• Dilated pupil size equal to or greater than 6 millimeters (mm) in primary study eye

• Other protocol-specified inclusion criteria may apply.

Exclusion Criteria:

• Participation in any other drug or device clinical trial within 30 days prior to enrolling in this study and/or during study participation

• History of any intraocular or corneal surgery in either eye (including refractive)

• History of any clinically significant retinal pathology or ocular diagnosis in either eye

• History of any ocular conditions which could affect the stability of the IOL

• Uncontrolled glaucoma in either eye

• Other protocol-specified exclusion criteria may apply.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	ClarVista Investigational Site	Auckland		New Zealand	1050
2	ClarVista Investigational Site	Makati City	Manila	Philippines	1200

Sponsors and Collaborators

• ClarVista Medical

Investigators

• Study Director: Sr. CDMA Project Lead, Surgical, Alcon Research, LLC

Study Documents (Full-Text)

• Study Protocol - Mar 14, 2016
• Statistical Analysis Plan - Feb 24, 2017

More Information

Publications

None provided.

• Responsible Party: ClarVista Medical
• ClinicalTrials.gov Identifier: NCT02521766
• Other Study ID Numbers: CP-00001
• First Posted: Aug 13, 2015
• Last Update Posted: May 14, 2020
• Last Verified: May 1, 2020

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: Yes
• Product Manufactured in and Exported from the U.S.: Yes
• Keywords provided by ClarVista Medical: Cataract; IOL; Modular IOL; IOL exchange
• Additional relevant MeSH terms: Cataract

Study Results

Participant Flow

Recruitment Details	Subjects were recruited from 3 investigational sites located in the Philippines (2) and New Zealand (1).
Pre-assignment Detail	Of the 217 enrolled, 101 subjects did exit the study prior to implantation, and 2 subjects failed implantation of Harmoni Modular Intraocular Lens (HMIOL). This reporting group includes all subjects with successful HMIOL implantation (114) by subgroup (Cohort 1 and Cohort 2).

Arm/Group Title	Cohort 1	Cohort 2
Arm/Group Description	HMIOL implantation with no optic exchange	HMIOL implantation with optic exchange
Period Title: Overall Study
STARTED	49	65
Per Protocol	47	65
COMPLETED	44	62
NOT COMPLETED	5	3

Baseline Characteristics

Arm/Group Title	Cohort 1	Cohort 2	Total
Arm/Group Description	HMIOL implantation with no optic exchange	HMIOL implantation with optic exchange	Total of all reporting groups
Overall Participants	47	65	112
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	66.8 (6.9)	65.4 (6.7)	66.0 (6.8)
Sex: Female, Male (Count of Participants)
Female	31 66%	40 61.5%	71 63.4%
Male	16 34%	25 38.5%	41 36.6%
Race/Ethnicity, Customized (Count of Participants)
Asian	28 59.6%	52 80%	80 71.4%
Black	0 0%	0 0%	0 0%
Caucasian	19 40.4%	11 16.9%	30 26.8%
Other	0 0%	2 3.1%	2 1.8%

Outcome Measures

1. Primary Outcome

Title	Percentage of Eyes With Postoperative BCDVA 20/40 Snellen or Better by Study Visit - All HMIOL Cohort
Description	Visual acuity (VA) was assessed using the Early Treatment Diabetic Retinopathy Study (ETDRS)-Fast method under well-lit conditions at a distance of 4 meters (m) with the correction obtained from manifest refraction testing. BCDVA was recorded in Snellen, with 20/20 considered to be 'normal' vision. A 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. This analysis was prespecified for the study eye. No formal statistical hypothesis testing was planned.
Time Frame	Month 1 postoperative, Month 3 postoperative

Outcome Measure Data

Analysis Population Description

Per Protocol Population, with available data at the visit

Arm/Group Title	All HMIOL Cohort
Arm/Group Description	HMIOL implantation with or without optic exchange
Measure Participants	112
Measure eyes	112
Month 1 postoperative	99.1
Month 3 postoperative	100.0

2. Primary Outcome

Title	Percentage of Eyes With Postoperative BCDVA 20/40 Snellen or Better by Study Visit - Cohort 1
Description	VA was assessed using the ETDRS-Fast method under well-lit conditions at a distance of 4 m with the correction obtained from manifest refraction testing. BCDVA was recorded in Snellen, with 20/20 considered to be 'normal' vision. A 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. This analysis was prespecified for the study eye. No formal statistical hypothesis testing was planned.
Time Frame	Month 1 postoperative, Month 3 postoperative, Month 6 postoperative, Month 12 postoperative

Outcome Measure Data

Analysis Population Description

Per Protocol Population, with available data at the visit

Arm/Group Title	Cohort 1
Arm/Group Description	HMIOL implantation with no optic exchange
Measure Participants	47
Measure eyes	47
Month 1 postoperative	100.0
Month 3 postoperative	100.0
Month 6 postoperative	100.0
Month 12 postoperative	100.0

3. Primary Outcome

Title	Percentage of Eyes With Postoperative BCDVA 20/40 Snellen or Better by Study Visit - Cohort 2
Description	VA was assessed using the ETDRS-Fast method under well-lit conditions at a distance of 4 m with the correction obtained from manifest refraction testing. BCDVA was recorded in Snellen, with 20/20 considered to be 'normal' vision. A 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. An optic exchange occurred at the Month 3 visit, after which subjects were followed for an additional 12 months. Month 1 postoperative and Month 3 postoperative visits were pre-optic exchange. This analysis was prespecified for the study eye. No formal statistical hypothesis testing was planned
Time Frame	Month 1 postoperative, Month 3 postoperative, Week 1 post-optic exchange, Month 1 post-optic exchange, Month 3 post-optic exchange, Month 6 post-optic exchange, Month 12 post-optic exchange

Outcome Measure Data

Analysis Population Description

Per Protocol Population, with available data at the visit

Arm/Group Title	Cohort 2
Arm/Group Description	HMIOL implantation with optic exchange
Measure Participants	65
Measure eyes	65
Month 1 postoperative	98.5
Month 3 postoperative	100
Week 1 post-optic exchange	100
Month 1 post-optic exchange	100
Month 3 post-optic exchange	100
Month 6 post-optic exchange	100
Month 12 post-optic exchange	96.8

4. Primary Outcome

Title	Percentage of Eyes With Postoperative BCDVA 20/40 Snellen or Better by Study Visit - Fellow Eye
Description	VA was assessed using the ETDRS-Fast method under well-lit conditions at a distance of 4 m with the correction obtained from manifest refraction testing. BCDVA was recorded in Snellen, with 20/20 considered to be 'normal' vision. A 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. This analysis was prespecified for the study eye. No formal statistical hypothesis testing was planned.
Time Frame	Month 1 postoperative, Month 3 postoperative, Month 12 postoperative

Outcome Measure Data

Analysis Population Description

Per Protocol Population, with available data at the visit

Arm/Group Title	Fellow Eye
Arm/Group Description	IOL implantation per standard of care
Measure Participants	111
Measure eyes	111
Month 1 postoperative	100.0
Month 3 postoperative	100.0
Month 12 postoperative	100.0

5. Primary Outcome

Title	Percentage of Eyes With Postoperative Manifest Refraction Spherical Equivalent (MRSE) Within Target by Study Visit - All HMIOL Cohort
Description	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). This analysis was prespecified for the study eye. No formal statistical hypothesis testing was planned.
Time Frame	Week 1 postoperative, Month 1 postoperative, Month 3 postoperative

Outcome Measure Data

Analysis Population Description

Per Protocol Population, with available data at the visit

Arm/Group Title	All HMIOL Cohort
Arm/Group Description	HMIOL implantation with or without optic exchange
Measure Participants	112
Measure eyes	112
Week 1 postoperative: Within ± 0.5 D of Target	33.9
Week 1 postoperative: Within ± 1.0 D of Target	70.6
Month 1 postoperative: Within ± 0.5 D of Target	26.8
Month 1 postoperative: Within ± 1.0 D of Target	61.6
Month 3 postoperative: Within ± 0.5 D of Target	19.6
Month 3 postoperative: Within ± 1.0 D of Target	52.7

6. Primary Outcome

Title	Percentage of Eyes With Postoperative Manifest Refraction Spherical Equivalent (MRSE) Within Target by Study Visit - Cohort 1
Description	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). This analysis was prespecified for the study eye. No formal statistical hypothesis testing was planned.
Time Frame	Week 1 postoperative, Month 1 postoperative, Month 3 postoperative, Month 6 postoperative, Month 12 postoperative

Outcome Measure Data

Analysis Population Description

Per Protocol Population, with available data at the visit

Arm/Group Title	Cohort 1
Arm/Group Description	HMIOL implantation with no optic exchange
Measure Participants	47
Measure eyes	47
Week 1 postoperative: Within ± 0.5 D of Target	31.1
Week 1 postoperative: Within ± 1.0 D of Target	57.8
Month 1 postoperative: Within ± 0.5 D of Target	23.4
Month 1 postoperative: Within ± 1.0 D of Target	48.9
Month 3 postoperative: Within ± 0.5 D of Target	19.1
Month 3 postoperative: Within ± 1.0 D of Target	44.7
Month 6 postoperative: Within ± 0.5 D of Target	14.9
Month 6 postoperative: Within ± 1.0 D of Target	44.7
Month 12 postoperative: Within ± 0.5 D of Target	20.9
Month 12 postoperative: Within ± 1.0 D of Target	37.2

7. Primary Outcome

Title	Percentage of Eyes With Postoperative Manifest Refraction Spherical Equivalent (MRSE) Within Target by Study Visit - Cohort 2
Description	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). An optic exchange occurred at the Month 3 visit, after which subjects were followed for an additional 12 months. Week 1 postoperative, Month 1 postoperative, and Month 3 postoperative visits were pre-optic exchange. This analysis was prespecified for the study eye. No formal statistical hypothesis testing was planned.
Time Frame	Week 1 postoperative, Month 1 postoperative, Month 3 postoperative, Week 1 post-optic exchange, Month 1 post-optic exchange, Month 3 post-optic exchange, Month 6 post-optic exchange, Month 12 post-optic exchange

Outcome Measure Data

Analysis Population Description

Per Protocol Population, with available data at the visit

Arm/Group Title	Cohort 2
Arm/Group Description	HMIOL implantation with optic exchange
Measure Participants	65
Measure eyes	65
Week 1 postoperative: Within ± 0.5 D of Target	35.9
Week 1 postoperative: Within ± 1.0 D of Target	79.7
Month 1 postoperative: Within ± 0.5 D of Target	29.2
Month 1 postoperative: Within ± 1.0 D of Target	70.8
Month 3 postoperative: Within ± 0.5 D of Target	20.0
Month 3 postoperative: Within ± 1.0 D of Target	58.5
Week 1 post-exchange: Within ± 0.5 D of Target	76.9
Week 1 post-exchange: Within ± 1.0 D of Target	98.5
Month 1 post-exchange: Within ± 0.5 D of Target	82.8
Month 1 post-exchange: Within ± 1.0 D of Target	100.0
Month 3 post-exchange: Within ± 0.5 D of Target	81.0
Month 3 post-exchange: Within ± 1.0 D of Target	98.4
Month 6 post-exchange: Within ± 0.5 D of Target	84.1
Month 6 post-exchange: Within ± 1.0 D of Target	100.0
Month 12 post-exchange: Within ± 0.5 D of Target	77.4
Month 12 post-exchange: Within ± 1.0 D of Target	95.2

8. Primary Outcome

Title	Percentage of Eyes With Postoperative Manifest Refraction Spherical Equivalent (MRSE) Within Target by Study Visit - Fellow Eye
Description	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). This analysis was prespecified for the fellow eye. No formal statistical hypothesis testing was planned.
Time Frame	Month 1 postoperative, Month 3 postoperative, Month 12 postoperative

Outcome Measure Data

Analysis Population Description

Per Protocol Population, with available data at the visit

Arm/Group Title	Fellow Eye
Arm/Group Description	IOL implantation per standard of care
Measure Participants	111
Measure eyes	111
Month 1 postoperative: Within ± 0.5 D of Target	78.5
Month 1 postoperative: Within ± 1.0 D of Target	98.1
Month 3 postoperative: Within ± 0.5 D of Target	81.1
Month 3 postoperative: Within ± 1.0 D of Target	99.1
Month 12 postoperative: Within ± 0.5 D of Target	72.2
Month 12 postoperative: Within ± 1.0 D of Target	97.2

9. Primary Outcome

Title	Mean BCDVA (Letters Read) by Study Visit - All HMIOL Cohort
Description	VA was assessed using the ETDRS-Fast method under well-lit conditions at a distance of 4 m with the correction obtained from manifest refraction testing. BCDVA was recorded in letters read correctly. This analysis was prespecified for the study eye. No formal statistical hypothesis testing was planned.
Time Frame	Day -90 to Day -1 preoperative, Month 1 postoperative, Month 3 postoperative

Outcome Measure Data

Analysis Population Description

Per Protocol Population, with available data at the visit

Arm/Group Title	All HMIOL Cohort
Arm/Group Description	HMIOL implantation with or without optic exchange
Measure Participants	112
Measure eyes	112
Day -90 to Day -1 preoperative	75.2 (14.2)
Month 1 postoperative	84.6 (4.5)
Month 3 postoperative	85.4 (3.8)

10. Primary Outcome

Title	Mean BCDVA (Letters Read) by Study Visit - Cohort 1
Description	VA was assessed using the ETDRS-Fast method under well-lit conditions at a distance of 4 m with the correction obtained from manifest refraction testing. BCDVA was recorded in letters read correctly. This analysis was prespecified for the study eye. No formal statistical hypothesis testing was planned.
Time Frame	Day -90 to -1 preoperative, Month 1 postoperative, Month 3 postoperative, Month 6 postoperative, Month 12 postoperative

Outcome Measure Data

Analysis Population Description

Per Protocol Population, with available data at the visit

Arm/Group Title	Cohort 1
Arm/Group Description	HMIOL implantation with no optic exchange
Measure Participants	47
Measure eyes	47
Day -90 to -1 preoperative	79.9 (9.4)
Month 1 postoperative	85.8 (3.6)
Month 3 postoperative	86.7 (3.5)
Month 6 postoperative	86.2 (3.9)
Month 12 postoperative	86.2 (4.5)

11. Primary Outcome

Title	Mean BCDVA (Letters Read) by Study Visit - Cohort 2
Description	VA was assessed using the ETDRS-Fast method under well-lit conditions at a distance of 4 m with the correction obtained from manifest refraction testing. BCDVA was recorded in letters read correctly. An optic exchange occurred at the Month 3 visit, after which subjects were followed for an additional 12 months. Month 1 postoperative and Month 3 postoperative visits were pre-optic exchange.This analysis was prespecified for the study eye. No formal statistical hypothesis testing was planned.
Time Frame	Day -90 to -1 preoperative, Month 1 postoperative, Month 3 postoperative, Week 1 post-optic exchange, Month 1 post-optic exchange, Month 3 post-optic exchange, Month 6 post-optic exchange, Month 12 post-optic exchange

Outcome Measure Data

Analysis Population Description

Per Protocol Population, with available data at the visit

Arm/Group Title	Cohort 2
Arm/Group Description	HMIOL implantation with optic exchange
Measure Participants	65
Measure eyes	65
Day -90 to -1 preoperative	71.8 (16.1)
Month 1 postoperative	83.7 (4.9)
Month 3 postoperative	84.4 (3.8)
Week 1 post-optic exchange	84.5 (4.4)
Month 1 post-optic exchange	85.1 (4.0)
Month 3 post-optic exchange	85.2 (4.0)
Month 6 post-optic exchange	85.6 (3.5)
Month 12 post-optic exchange	83.5 (9.9)

12. Primary Outcome

Title	Mean BCDVA (Letters Read) by Study Visit - Fellow Eye
Description	VA was assessed using the ETDRS-Fast method under well-lit conditions at a distance of 4 m with the correction obtained from manifest refraction testing. BCDVA was rrecorded in letters read correctly. This analysis was prespecified for the fellow eye. No formal statistical hypothesis testing was planned.
Time Frame	Day -90 to -1 preoperative, Month 1 postoperative, Month 3 postoperative, Month 12 postoperative

Outcome Measure Data

Analysis Population Description

Per Protocol Population, with available data at the visit

Arm/Group Title	Fellow Eye
Arm/Group Description	IOL implantation per standard of care
Measure Participants	114
Measure eyes	114
Day -90 to -1 preoperative	74.5 (17.9)
Month 1 postoperative	86.3 (4.0)
Month 3 postoperative	86.9 (3.4)
Month 12 postoperative	86.9 (3.5)

13. Primary Outcome

Title	Mean Uncorrected Distance Visual Acuity (UCDVA) (Letters Read) by Study Visit - All HMIOL Cohort
Description	VA was assessed using the ETDRS-Fast method under well-lit conditions at a distance of 4 m with an optical infinity adjustment of +0.25 diopter (D). UCDVA was recorded in letters read correctly. This analysis was prespecified for the study eye. No formal statistical hypothesis testing was planned.
Time Frame	Day 1 postoperative, Week 1 postoperative, Month 1 postoperative, Month 3 postoperative

Outcome Measure Data

Analysis Population Description

Per Protocol Population, with available data at the visit

Arm/Group Title	All HMIOL Cohort
Arm/Group Description	HMIOL implantation with or without optic exchange
Measure Participants	112
Measure eyes	112
Day 1 postoperative	71.5 (11.0)
Week 1 postoperative	70.4 (10.1)
Month 1 postoperative	70.6 (10.2)
Month 3 postoperative	73.4 (9.3)

14. Primary Outcome

Title	Mean Uncorrected Distance Visual Acuity (UCDVA) (Letters Read) by Study Visit - Cohort 1
Description	VA was assessed using the ETDRS-Fast method under well-lit conditions at a distance of 4 m with an optical infinity adjustment of +0.25 diopter (D). UCDVA was recorded in letters read correctly. This analysis was prespecified for the study eye. No formal statistical hypothesis testing was planned.
Time Frame	Day 1 postoperative, Week 1 postoperative, Month 1 postoperative, Month 3 postoperative, Month 6 postoperative, Month 12 postoperative

Outcome Measure Data

Analysis Population Description

Per Protocol Population, with available data at the visit

Arm/Group Title	Cohort 1
Arm/Group Description	HMIOL implantation with no optic exchange
Measure Participants	47
Measure eyes	47
Day 1 postoperative	74.8 (10.2)
Week 1 postoperative	73.7 (9.2)
Month 1 postoperative	75.4 (8.3)
Month 3 postoperative	77.1 (8.2)
Month 6 postoperative	78.1 (7.3)
Month 12 postoperative	77.9 (6.9)

15. Primary Outcome

Title	Mean Uncorrected Distance Visual Acuity (UCDVA) (Letters Read) by Study Visit - Cohort 2
Description	VA was assessed using the ETDRS-Fast method under well-lit conditions at a distance of 4 m with an optical infinity adjustment of +0.25 diopter (D). UCDVA was recorded in letters read correctly. An optic exchange occurred at the Month 3 visit, after which subjects were followed for an additional 12 months. Day 1 postoperative, Week 1 postoperative, Month 1 postoperative, and Month 3 postoperative visits were pre-optic exchange. This analysis was prespecified for the study eye. No formal statistical hypothesis testing was planned.
Time Frame	Day 1 postoperative, Week 1 postoperative, Month 1 postoperative, Month 3 postoperative, Day 1 post-optic exchange, Week 1 post-optic exchange, Month 1 post-optic exchange, Month 3 post-optic exchange, Month 6 post-optic exchange, Month 12 post-optic exch

Outcome Measure Data

Analysis Population Description

Per Protocol Population, with available data at the visit

Arm/Group Title	Cohort 2
Arm/Group Description	HMIOL implantation with optic exchange
Measure Participants	65
Measure eyes	65
Day 1 postoperative	69.1 (10.9)
Week 1 postoperative	68.1 (10.2)
Month 1 postoperative	67.2 (10.2)
Month 3 postoperative	70.7 (9.2)
Day 1 post-optic exchange	76.8 (13.4)
Week 1 post-optic exchange	79.8 (6.0)
Month 1 post-optic exchange	80.7 (6.4)
Month 3 post-optic exchange	81.1 (5.5)
Month 6 post-optic exchange	81.2 (5.4)
Month 12 post-optic exchange	78.2 (13.4)

16. Primary Outcome

Title	Mean Uncorrected Distance Visual Acuity (UCDVA) (Letters Read) by Study Visit - Fellow Eye
Description	VA was assessed using the ETDRS-Fast method under well-lit conditions at a distance of 4 m with an optical infinity adjustment of +0.25 diopter (D). UCDVA was recorded in letters read correctly. This analysis was prespecified for the fellow eye. No formal statistical hypothesis testing was planned.
Time Frame	Day 1 postoperative, Week 1 postoperative, Month 1 postoperative, Month 3 postoperative, Month 6 postoperative, Month 12 postoperative

Outcome Measure Data

Analysis Population Description

Per Protocol Population, with available data at the visit

Arm/Group Title	Fellow Eye
Arm/Group Description	IOL implantation per standard of care
Measure Participants	114
Measure eyes	114
Day 1 postoperative	80.6 (8.0)
Week 1 postoperative	81.3 (6.4)
Month 1 postoperative	81.3 (5.8)
Month 3 postoperative	82.4 (5.4)
Month 6 postoperative	83.0 (5.0)
Month 12 postoperative	82.1 (5.5)

17. Primary Outcome

Title	Percentage of Eyes With UCDVA by Category (Snellen) for Each Post-optic Exchange Study Visit - Cohort 2
Description	VA was assessed using the ETDRS-Fast method under well-lit conditions at a distance of 4 m with an optical infinity adjustment of +0.25 diopter (D). UCDVA was recorded in Snellen, with 20/20 considered to be 'normal' vision. A 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. An optic exchange occurred at the Month 3 visit, after which subjects were followed for an additional 12 months. Day 1 postoperative, Week 1 postoperative, Month 1 postoperative, and Month 3 postoperative visits were pre-optic exchange. This analysis was prespecified for the study eye, Cohort 2 only. No formal statistical hypothesis testing was planned.
Time Frame	Day 1 post-optic exchange, Week 1 post-optic exchange, Month 1 post-optic exchange, Month 3 post-optic exchange, Month 6 post-optic exchange, Month 12 post-optic exchange

Outcome Measure Data

Analysis Population Description

Per Protocol Population, with available data at the visit

Arm/Group Title	Cohort 2 Day 1 Post-optic Exchange	Cohort 2 Week 1 Post-optic Exchange	Cohort 2 Month 1 Post-optic Exchange	Cohort 2 Month 3 Post-optic Exchange	Cohort 2 Month 6 Post-optic Exchange	Cohort 2 Month 12 Post-optic Exchange
Arm/Group Description	HMIOL implantation with optic exchange	HMIOL implantation with optic exchange	HMIOL implantation with optic exchange	HMIOL implantation with optic exchange	HMIOL implantation with optic exchange	HMIOL implantation with optic exchange
Measure Participants	65	65	64	63	63	62
Measure eyes	65	65	64	63	63	63
20/20 Snellen or Better	41.5	47.7	53.1	49.2	55.6	50.0
20/25 Snellen or Better	67.7	69.2	70.3	81.0	79.4	74.2
20/32 Snellen or Better	80.0	87.7	92.2	93.7	93.7	83.9
20/40 Snellen or Better	87.7	93.8	96.9	96.8	98.4	95.2
Worse than 20/40 Snellen	12.3	6.2	3.1	3.2	1.6	4.8

18. Primary Outcome

Title	Mesopic Best Corrected Distance Visual Acuity (mBCDVA) (With and Without Glare) (Letters Read) at Study Visit - All HMIOL Cohort
Description	VA was assessed using the ETDRS-Fast method under mesopic (dimly lit) conditions at a distance of 4 m with the correction obtained from manifest refraction testing. Testing was performed with and without glare. Chart luminance was set to 3 cd/m2. mBCDVA was recorded in letters read correctly. This analysis was prespecified for the study eye, All HMIOL Cohort only. No formal statistical hypothesis testing was planned.
Time Frame	Month 3 postoperative

Outcome Measure Data

Analysis Population Description

Per Protocol Population, with available data at the visit

Arm/Group Title	All HMIOL Cohort
Arm/Group Description	HMIOL implantation with or without optic exchange
Measure Participants	112
Measure eyes	112
With glare	81.0 (4.9)
Without glare	81.1 (5.6)

Adverse Events

Time Frame	Adverse events (AEs) were collected from time of consent until study: Cohort 1: Up to 15 months, including a Day -90 to Day -1 preoperative period and a 12 month post-operative follow-up period. Cohort 2: Up to 18 months, including a Day -90 to Day -1 preoperative period, an optic exchange at Month 3 postoperative, and a 12 month post-exchange follow-up period. "At Risk" population of systemic AEs is reported in units of subjects; all other AE populations are reported in units of eyes.
Adverse Event Reporting Description	Safety Analysis Population: All eyes with attempted study lens (HMIOL) implantation (successful or aborted after contact with the eye).
Arm/Group Title	Cohort 1 (Ocular)		Cohort 2 Pre-exchange (Ocular)		Cohort 2 Post-exchange (Ocular)		Fellow Eye (Ocular)		Systemic (Non-ocular)
Arm/Group Description	HMIOL implantation with no optic exchange Events reported in this group occurred in the study eye from time of consent to study exit (up to 15 months)		HMIOL implantation pre-optic exchange Events reported in this group occurred in the study eye from time of consent to time of optic exchange (up to 6 months)		HMIOL implantation post-optic exchange Events reported in this group occurred in the study eye from time of optic exchange to time of study exit (up to 12 months)		IOL per standard of care Events reported in this group occurred in the fellow eye from time of consent to study exit (up to 15 months if study eye was enrolled in Cohort 1, up to 18 months if study eye was enrolled in Cohort 2)		Events reported in this group occurred from time of consent to study exit (up to 15 months if subject was enrolled in Cohort 1, up to 18 months if subject was enrolled in Cohort 2)
All Cause Mortality
	Cohort 1 (Ocular)		Cohort 2 Pre-exchange (Ocular)		Cohort 2 Post-exchange (Ocular)		Fellow Eye (Ocular)		Systemic (Non-ocular)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/51 (0%)		0/65 (0%)		0/65 (0%)		0/114 (0%)		0/114 (0%)
Serious Adverse Events
	Cohort 1 (Ocular)		Cohort 2 Pre-exchange (Ocular)		Cohort 2 Post-exchange (Ocular)		Fellow Eye (Ocular)		Systemic (Non-ocular)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/51 (3.9%)		2/65 (3.1%)		0/65 (0%)		2/114 (1.8%)		4/114 (3.5%)
Cardiac disorders
Acute myocardial infarction	0/51 (0%)		0/65 (0%)		0/65 (0%)		0/114 (0%)		1/114 (0.9%)
Eye disorders
Endophthalmitis	0/51 (0%)		0/65 (0%)		0/65 (0%)		1/114 (0.9%)		0/114 (0%)
Neovascular age-related macular degeneration	0/51 (0%)		0/65 (0%)		0/65 (0%)		1/114 (0.9%)		0/114 (0%)
Posterior Capsule Rupture	1/51 (2%)		0/65 (0%)		0/65 (0%)		0/114 (0%)		0/114 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Breast cancer stage II	0/51 (0%)		0/65 (0%)		0/65 (0%)		0/114 (0%)		1/114 (0.9%)
Nervous system disorders
Cerebrovascular accident	0/51 (0%)		0/65 (0%)		0/65 (0%)		0/114 (0%)		1/114 (0.9%)
Parkinsonism	0/51 (0%)		0/65 (0%)		0/65 (0%)		0/114 (0%)		1/114 (0.9%)
Surgical and medical procedures
Eye operation	0/51 (0%)		1/65 (1.5%)		0/65 (0%)		0/114 (0%)		0/114 (0%)
Intraocular lens implant	1/51 (2%)		0/65 (0%)		0/65 (0%)		0/114 (0%)		0/114 (0%)
Surgery	0/51 (0%)		1/65 (1.5%)		0/65 (0%)		0/114 (0%)		0/114 (0%)
Other (Not Including Serious) Adverse Events
	Cohort 1 (Ocular)		Cohort 2 Pre-exchange (Ocular)		Cohort 2 Post-exchange (Ocular)		Fellow Eye (Ocular)		Systemic (Non-ocular)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/51 (3.9%)		1/65 (1.5%)		6/65 (9.2%)		5/114 (4.4%)		0/114 (0%)
Eye disorders
Dry eye	2/51 (3.9%)		1/65 (1.5%)		6/65 (9.2%)		5/114 (4.4%)		0/114 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

Sponsor reserves the right of prior review of any publication or presentation of information related to the study.