← Product Code [MFK](/productcode/MFK) · P980040S124

# TECNIS Synergy Intraocular Lens, TECNIS Synergy Toric II Intraocular Lens, TECNIS Synergy IOL with TECNIS Simplicity Del (P980040S124)

_Johnson & Johnson Surgical Vision, Inc. · MFK · Apr 28, 2021 · Ophthalmic · APPR_

**Canonical URL:** https://fda.innolitics.com/device/P980040S124

## Device Facts

- **Applicant:** Johnson & Johnson Surgical Vision, Inc.
- **Product Code:** [MFK](/productcode/MFK.md)
- **Decision Date:** Apr 28, 2021
- **Decision:** APPR
- **Regulation:** 21 CFR 886.3600
- **Device Class:** Class 3
- **Review Panel:** Ophthalmic
- **Attributes:** Therapeutic

## Indications for Use

The TECNIS Synergy™ IOL, Model ZFR00V, is indicated for primary implantation for the visual correction of aphakia in adult patients, with less than 1 diopter of pre-existing corneal astigmatism, in whom a cataractous lens has been removed. Compared to an aspheric monofocal lens, the TECNIS Synergy™ IOL mitigates the effects of presbyopia by providing improved visual acuity at intermediate and near distances to reduce eyeglass wear, while maintaining comparable distance visual acuity. The lens is intended for capsular bag placement only. The TECNIS Synergy™ Toric II IOL, Models ZFW150, ZFW225, ZFW300, ZFW375, are indicated for primary implantation for the visual correction of aphakia and for the reduction of refractive astigmatism in adult patients with greater than or equal to 1 diopter of preoperative corneal astigmatism, in whom a cataractous lens has been removed. Compared to an aspheric monofocal lens, the TECNIS Synergy™ Toric II IOLs mitigate the effects of presbyopia by providing improved visual acuity at intermediate and near distances to reduce eyeglass wear while maintaining comparable distance visual acuity. The lens is intended for capsular bag placement only. The TECNIS Simplicity™ Delivery System is used to fold and assist in inserting the TECNIS Synergy™ IOL which is indicated for primary implantation for the visual correction of aphakia in adult patients, with less than 1 diopter of pre-existing corneal astigmatism, in whom a cataractous lens has been removed. Compared to an aspheric monofocal lens, the TECNIS Synergy™ IOL mitigates the effects of presbyopia by providing improved visual acuity at intermediate and near distances to reduce eyeglass wear, while maintaining comparable distance visual acuity. The lens is intended for capsular bag placement only. The TECNIS Simplicity™ Delivery System is used to fold and assist in inserting the TECNIS Synergy™ Toric II IOLs that are indicated for primary implantation for the visual correction of aphakia and for reduction of refractive astigmatism in adult patients with greater than or equal to 1 diopter of preoperative corneal astigmatism, in whom a cataractous lens has been removed. Compared to an aspheric monofocal lens, the TECNIS Synergy™ Toric II IOLs mitigate the effects of presbyopia by providing improved visual acuity at intermediate and near distances to reduce eyeglass wear while maintaining comparable distance visual acuity. The lens is intended for capsular bag placement only.

## Device Story

TECNIS Synergy™ IOLs are UV-absorbing, posterior chamber, one-piece acrylic intraocular lenses (IOLs) designed to replace the natural crystalline lens after cataract surgery. The device utilizes a proprietary wavefront-designed aspheric or toric-aspheric anterior optic and a posterior optic with combined diffractive multifocal and extended depth of focus (EDF) technology. This design provides continuous 20/32 or better visual acuity from distance to 33 cm. Toric models include axis orientation marks to correct astigmatism. The device is implanted by a surgeon in an OR setting using validated insertion systems or the preloaded TECNIS Simplicity™ Delivery System. The lens provides patients with improved intermediate and near vision, reducing spectacle dependence compared to monofocal IOLs. Healthcare providers use the JJSV TECNIS Toric Calculator to select the appropriate model based on patient needs. The output is improved visual range, though patients may experience visual symptoms like halos or glare.

## Clinical Evidence

Prospective, multicenter, bilateral, randomized, 6-month clinical study (N=272) comparing TECNIS Synergy™ IOL to monofocal control (TECNIS ZCB00). Primary endpoint: monocular photopic DCNVA at 40 cm. Results: Synergy group showed statistically significant improvement in DCNVA (0.104 LogMAR vs 0.522 LogMAR, p<0.0001). Secondary endpoints: DCIVA at 66 cm (0.060 LogMAR vs 0.335 LogMAR, p<0.0001) and spectacle independence (87.8% vs 3.1% reporting 'none of the time'). Safety: AE rates were comparable to control and within ISO 11979-7 SPE rates. Contrast sensitivity was lower for Synergy but not clinically significant.

## Technological Characteristics

One-piece violet-light filtering soft acrylic IOL with polyethylene glycol surface treatment. Optic diameter 6.0 mm, overall 13.0 mm. Wavefront-designed aspheric or toric-aspheric anterior surface; posterior diffractive surface (EDF/multifocal combination). UV cut-off 420-430 nm. Sterilization: Ethylene Oxide. Standards: ISO 11979-2, ISO 11979-3, ANSI Z80.30, ANSI Z80.35, ANSI Z80.12. Delivery: Daisywheel packaging or preloaded TECNIS Simplicity™ Delivery System.

## Regulatory Identification

An intraocular lens is a device made of materials such as glass or plastic intended to be implanted to replace the natural lens of an eye.

## Predicate Devices

- TECNIS multifocal ZM900 ([P080010](/device/P080010.md))
- TECNIS Symfony ZXR00 ([P980040](/device/P980040.md)/S065)
- TECNIS Toric 1-Piece ZCT ([P980040](/device/P980040.md)/S039)
- TECNIS OptiBlue ZV9003 ([P980040](/device/P980040.md)/S035)

## Reference Devices

- TECNIS 1-Piece OptiBlue IOL Model ZCB00V ([P980040](/device/P980040.md)/S035)
- TECNIS 1-Piece IOL Model ZCB00 (monofocal control)
- SENSAR 1-Piece IOL Model AAB00 ([P980040](/device/P980040.md)/S015)

## Submission Summary (Full Text)

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>
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Summary of Safety and Effectiveness Data (SSED)  
TECNIS Synergy™ IOLs, Models ZFR00V, DFR00V, ZFW150, ZFW225, ZFW300, ZFW375, DFW150,  
DFW225, DFW300 and DFW375

# SUMMARY OF SAFETY AND EFFECTIVENESS DATA (SSED)

## I. GENERAL INFORMATION

|  Device Generic Name: | Intraocular Lens  |
| --- | --- |
|  Device Trade Name: | - TECNIS Synergy™ IOL, Model ZFR00V - TECNIS Synergy™ Toric II IOL, Models ZFW150, ZFW225, ZFW300, ZFW375 - TECNIS Synergy™ IOL with TECNIS Simplicity™ Delivery System, Model DFR00V - TECNIS Synergy™ Toric II IOL with TECNIS Simplicity™ Delivery System, Model DFW150, DFW225, DFW300, DFW375  |
|  Device Procode: | Multifocal Intraocular (MFK)  |
|  Applicant’s Name and Address: | Johnson & Johnson Surgical Vision, Inc. 1700 East Saint Andrew Place Santa Ana, CA 92705  |
|  Date(s) of Panel Recommendation: | None  |
|  Premarket Approval Application (PMA) Number: | P980040/S124  |
|  Date of FDA Notice of Approval: |   |

The TECNIS Synergy™ multifocal intraocular lens (Daisywheel configuration Model ZFR00V and Simplicity™ preloaded configuration DFW00V) and toric multifocal lenses (Daisywheel configuration ZFW150, ZFW225, ZFW300, and ZFW375; Simplicity™ preloaded configuration DFW150, DFW225, DFW300 and DFW375) are based on the TECNIS multifocal ZM900 and TECNIS Symfony ZXR00 optical parents, the TECNIS Toric 1-Piece ZCT toric parent, and the TECNIS OptiBlue ZV9003 material parent. These were approved under PMAs P080010 (January 9, 2009), P980040/S065 (July 15, 2016), P980040/S039 (April 12, 2013), and P980040/S035 (September 12, 2012), respectively. The optical parents and toric parent devices have the following Indications for Use:

TECNIS multifocal intraocular lens is indicated for primary implantation for the visual correction of aphakia in adult patients with and without presbyopia in whom

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Summary of Safety and Effectiveness Data (SSED)
TECNIS Synergy™ IOLs, Models ZFR00V, DFR00V, ZFW150, ZFW225, ZFW300, ZFW375, DFW150, DFW225, DFW300 and DFW375

a cataractous lens has been removed by phacoemulsification and who desire near, intermediate, and distance vision with increased spectacle independence. The intraocular lenses are intended to be placed in the capsular bag.

The TECNIS Symfony Extended Range of Vision IOL, Model ZXR00, is indicated for primary implantation for the visual correction of aphakia, in adult patients with less than 1 diopter of pre-existing corneal astigmatism, in whom a cataractous lens has been removed. The lens mitigates the effects of presbyopia by providing an extended depth of focus. Compared to an aspheric monofocal IOL, the lens provides improved intermediate and near visual acuity, while maintaining comparable distance visual acuity. The Model ZXR00 IOL is intended for capsular bag placement only.

The TECNIS Toric 1-piece posterior chamber lenses are indicated for the visual correction of aphakia and pre-existing corneal astigmatism of one diopter or greater in adult patients with or without presbyopia in whom a cataractous lens has been removed by phacoemulsification and who desire improved uncorrected distance vision, reduction in residual refractive cylinder and increased spectacle independence for distance vision. The device is intended to be placed in the capsular bag.

The SSEDs to support the indications are available on the CDRH website and are incorporated by reference here:

- https://www.accessdata.fda.gov/cdrh_docs/pdf8/P080010b.pdf
- https://www.accessdata.fda.gov/cdrh_docs/pdf/P980040S065B.pdf
- https://www.accessdata.fda.gov/cdrh_docs/pdf/P980040S039b.pdf

The current supplement was submitted to modify the indications and include the TECNIS Synergy™ IOL, Model ZFR00V, TECNIS Synergy™ Toric II IOL, Models ZFW150, ZFW225, ZFW300, ZFW375, the TECNIS Synergy™ IOL with TECNIS Simplicity™ Delivery System, Model DFR00V, and the TECNIS Synergy™ Toric II IOL with TECNIS Simplicity™ Delivery System, Models DFW150, DFW225, DFW300, DFW375.

## **II. INDICATIONS FOR USE**

### **TECNIS Synergy™ IOL, Model ZFR00V**

The TECNIS Synergy™ IOL, Model ZFR00V, is indicated for primary implantation for the visual correction of aphakia in adult patients, with less than 1 diopter of pre-existing corneal astigmatism, in whom a cataractous lens has been removed. Compared to an aspheric monofocal lens, the TECNIS Synergy™ IOL mitigates the effects of presbyopia by providing improved visual acuity at intermediate and near distances to reduce eyeglass

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Summary of Safety and Effectiveness Data (SSED)  
TECNIS Synergy™ IOLs, Models ZFR00V, DFR00V, ZFW150, ZFW225, ZFW300, ZFW375, DFW150,  
DFW225, DFW300 and DFW375

wear, while maintaining comparable distance visual acuity. The lens is intended for capsular bag placement only.

# **TECNIS Synergy™ Toric II IOL, Models ZFW150, ZFW225, ZFW300, ZFW375**

The TECNIS Synergy™ Toric II IOL, Models ZFW150, ZFW225, ZFW300, ZFW375, are indicated for primary implantation for the visual correction of aphakia and for the reduction of refractive astigmatism in adult patients with greater than or equal to 1 diopter of preoperative corneal astigmatism, in whom a cataractous lens has been removed. Compared to an aspheric monofocal lens, the TECNIS Synergy™ Toric II IOLs mitigate the effects of presbyopia by providing improved visual acuity at intermediate and near distances to reduce eyeglass wear while maintaining comparable distance visual acuity. The lens is intended for capsular bag placement only.

# **TECNIS Synergy™ IOL with TECNIS Simplicity™ Delivery System, Model DFR00V**

The TECNIS Simplicity™ Delivery System is used to fold and assist in inserting the TECNIS Synergy™ IOL which is indicated for primary implantation for the visual correction of aphakia in adult patients, with less than 1 diopter of pre-existing corneal astigmatism, in whom a cataractous lens has been removed. Compared to an aspheric monofocal lens, the TECNIS Synergy™ IOL mitigates the effects of presbyopia by providing improved visual acuity at intermediate and near distances to reduce eyeglass wear, while maintaining comparable distance visual acuity. The lens is intended for capsular bag placement only.

# **TECNIS Synergy™ Toric II IOL with TECNIS Simplicity™ Delivery System, Models DFW150, DFW225, DFW300, DFW375**

The TECNIS Simplicity™ Delivery System is used to fold and assist in inserting the TECNIS Synergy™ Toric II IOLs that are indicated for primary implantation for the visual correction of aphakia and for reduction of refractive astigmatism in adult patients with greater than or equal to 1 diopter of preoperative corneal astigmatism, in whom a cataractous lens has been removed. Compared to an aspheric monofocal lens, the TECNIS Synergy™ Toric II IOLs mitigate the effects of presbyopia by providing improved visual acuity at intermediate and near distances to reduce eyeglass wear, while maintaining comparable distance visual acuity. The lens is intended for capsular bag placement only.

### III. CONTRAINDICATIONS

There are no known contraindications.

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Summary of Safety and Effectiveness Data (SSED)

TECNIS Synergy™ IOLs, Models ZFR00V, DFR00V, ZFW150, ZFW225, ZFW300, ZFW375, DFW150,

DFW225, DFW300 and DFW375

#### IV. WARNINGS AND PRECAUTIONS

The warnings and precautions can be found in the labeling for the TECNIS Synergy™ IOLs.

#### V. DEVICE DESCRIPTION

The TECNIS Synergy™ IOLs, non-toric lens models ZFR00V/DFR00V and toric lens Models ZFW150/DFW150, ZFW225/DFW225, ZFW300/DFW300, ZFW375/DFW375, are ultraviolet light-absorbing posterior chamber IOLs that provide far vision comparable to an aspheric monofocal IOL and continuous 20/32 or better visual acuity through at least -3.0 D of defocus, which corresponds to distances ranging from approximately 33 cm to infinity. Compared to an aspheric monofocal IOL, the lens provides significantly improved near vision, including in low-light conditions. The lens material blocks UV and violet radiation up to a 10%T cutoff wavelength of 420 nm to 430 nm. In addition, the toric IOLs compensate for corneal astigmatism. TECNIS Synergy™ IOLs are to be positioned in the lens capsule to replace the optical function of the natural crystalline lens. Accommodation will not be restored. Table 1 below describes the physical characteristics of the lenses. The biconvex optic incorporates a proprietary wavefront-designed aspheric or toric-aspheric anterior optic, designed to compensate for corneal spherical aberration. The anteriorly located cylinder axis marks in the toric-aspheric optic denote the meridian with the lowest power and are to be aligned with the steep corneal meridian. The squared posterior edge of the aspheric and toric-aspheric anterior optic provide a 360-degree barrier and has a frosted design to reduce potential edge glare effects. The TECNIS Synergy™ IOLs share the same one-piece lens platform, the same material, lens geometry, general dimensions, overall manufacturing process, and packaging configuration as their parent lens models, and incorporate a proprietary diffractive technology on the posterior optic that is a combination of the multifocal and extended depth of focus (EDF) technologies derived from the optical parents. The unique design features of the TECNIS Synergy™ IOLs provide far vision comparable to an aspheric monofocal IOL and continuous 20/32 or better vision from 0.0 D through at least -3.0 D of defocus. This corresponds to a distance ranging from optical infinity to 33 cm. The posterior optic of the lens has a diffractive surface derived from a combination of EDF and multifocal technologies and is designed to correct chromatic aberration and provide a range of vision from distance to intermediate to near. The TECNIS Synergy™ IOLs demonstrated pupil-independent lens performance among the pupil sizes tested (>2.5 mm).

The optic is 6.0 mm in diameter and the lens has an overall diameter of 13.0 mm. The toric lenses incorporate perpendicular maximum and minimum radii of curvature and two sets of four (total of eight) axis orientation marks on their anterior optic surfaces that correct astigmatic refractive error when aligned properly with the patient's corneal astigmatism

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Summary of Safety and Effectiveness Data (SSED)

TECNIS Synergy™ IOLs, Models ZFR00V, DFR00V, ZFW150, ZFW225, ZFW300, ZFW375, DFW150, DFW225, DFW300 and DFW375

(predicted postoperative steep corneal meridian). The physical properties of this lens are shown in Figure 1 and the packaging configurations are shown in Figure 2. The implantation systems validated for use with the TECNIS Synergy™ IOLs packaged in the Daisywheel packaging (Models ZFR00V, ZFW150-375) are the UNFOLDER Platinum One Series Implantation system with the 1MTEC30 cartridge, the ONE SERIES Ultra Insertion System (the 1VPR30 Cartridge and the DK7786 or DK7791 inserters) and the UNFOLDER® EMERALD-AR Series Implantation System (with the 1CART30 Cartridge). The TECNIS Synergy™ IOLs packaged with the TECNIS Simplicity™ Delivery System (Models DFR00V, DFW150-375) are preloaded to provide a sterile, single-use, controlled and touch-free disposable system that functions as both the primary packaging and as part of an insertion system for IOL insertion into the eye during cataract surgery.

The conversion table for cylinder powers is provided below:

|  IOL Model | Cylinder Power (D)  |   |
| --- | --- | --- |
|   |  IOL Plane (Labeled) | Corneal Plane*  |
|  ZFW150 | 1.50 | 1.03  |
|  ZFW225 | 2.25 | 1.54  |
|  ZFW300 | 3.00 | 2.06  |
|  ZFW375 | 3.75 | 2.57  |

Light Transmittance: UV cut-off at 10% T for a spherical equivalent (SE) +5.0 diopter lens (thinnest), SE +20.0 diopter lens and a SE +34.0 diopter lens (thickest) are shown in Figure 3.

The JJSV TECNIS Toric Calculator is a web-based calculator tool that can be used to select the most appropriate TECNIS Synergy™ Toric II IOL that best suits the visual needs of the patient. The TECNIS Toric Calculator is developed and controlled by JJSV's Software Development Procedures.

Table 1
Summary of Physical Characteristics

|  Attribute | Non-Toric TECNIS SynergyTM IOL, Model ZFR00V and DFR00V | Toric TECNIS SynergyTM IOL, Model ZFW150-375 and DFW150-375  |
| --- | --- | --- |
|  Lens Design | 1-piece acrylic IOL with aspheric anterior surface | 1-piece acrylic IOL with aspheric toric anterior surface  |
|  Lens Material | Violet-light filtering soft acrylic material with polyethylene glycol surface treatment  |   |
|  Optic diameter | 6.00 mm  |   |
|  Overall Diameter | 13.00 mm  |   |
|  Haptic Style | C-Loop Tumble polished | C-Loop Squared, frosted  |
|  Haptic angle | No angulation but offset from optic body  |   |

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Summary of Safety and Effectiveness Data (SSED)

TECNIS Synergy™ IOLs, Models ZFR00V, DFR00V, ZFW150, ZFW225, ZFW300, ZFW375, DFW150, DFW225, DFW300 and DFW375

|  Attribute | Non-Toric TECNIS SynergyTM IOL, Model ZFR00V and DFR00V | Toric TECNIS SynergyTM IOL, Model ZFW150-375 and DFW150-375  |
| --- | --- | --- |
|  Diopter Power Range | Spherical equivalent: +5.0 D to +34.0 D in 0.5 D increments | Spherical equivalent: +5.0 D to +34.0 D in 0.5 D incrementsCylinder power:Model ZFW150/DFW150: 1.50DModel ZFW225/DFW225: 2.25DModel ZFW300/DFW300: 3.00DModel ZFW375/DFW375: 3.75D  |
|  Corneal Plane, approximate (Diopter) | 0.0 | Model ZFW150/DFW150: 1.03DModel ZFW225/DFW225: 1.54DModel ZFW300/DFW300: 2.06DModel ZFW375/DFW375: 2.57D  |
|  Refractive Index | 1.471 (35°C)  |   |
|  Range of Vision | Through -3.0D  |   |

Figure 1

Mechanical Drawings

TECNIS Synergy™ IOLs

TECNIS Synergy™ Toric II IOLs

![img-0.jpeg](img-0.jpeg)

![img-1.jpeg](img-1.jpeg)

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Summary of Safety and Effectiveness Data (SSED)

TECNIS Synergy™ IOLs, Models ZFR00V, DFR00V, ZFW150, ZFW225, ZFW300, ZFW375, DFW150, DFW225, DFW300 and DFW375

Figure 2

Packaging Configurations

Daisywheel Packaging

![img-2.jpeg](img-2.jpeg)

TECNIS Simplicity™ Packaging

![img-3.jpeg](img-3.jpeg)

Figure 3

Spectral Transmittance Curve

![img-4.jpeg](img-4.jpeg)

# Legend:

Spectral transmittance curve of a typical 5-diopter IOL (thinnest). UV(420): UV cut-off at 10%T is 420 nm.

Spectral transmittance curve of a typical 20-diopter IOL. UV(424): UV cut-off at 10%T is 424 nm.

Spectral transmittance curve of a typical 34-diopter IOL (thickest). UV(426): UV cut-off at 10%T is 426 nm.

Spectral transmittance curve of crystalline lenses: 30 year old and 40-49 year old from Artigas, J.M., Felipe, A., Navea, A.,

Fandino, A., & Artigas, C. Spectral transmission of the human crystalline lens in adult and elderly persons: color and total

transmission of visible light. Invest Ophthalmol Vis Sci (2012);53(7):4076-4084. 53 year old from Boettner, E.A., and Wolter J.R.

Transmission of the Ocular Media. Investigative Ophthalmology. 1962;1:776-783.

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Summary of Safety and Effectiveness Data (SSED)  
TECNIS Synergy™ IOLs, Models ZFR00V, DFR00V, ZFW150, ZFW225, ZFW300, ZFW375, DFW150,  
DFW225, DFW300 and DFW375

## VI. ALTERNATIVE PRACTICES AND PROCEDURES

There are several other alternatives for the correction of aphakia resulting from surgical cataract removal (i.e., for patients who have had a cataractous lens removed). Nonsurgical options include eyeglasses or contact lenses. Surgical options come in the form of intraocular lenses, which may be monofocal, multifocal, extended depth of focus, toric or accommodative, depending on the patient’s needs, expectations, and lifestyle. Each alternative has its own advantages and disadvantages. A patient should fully discuss these alternatives with his/her physician to select the method that best meets expectations and lifestyle.

## VII. MARKETING HISTORY

The TECNIS Synergy™ IOLs in select models are currently commercially available in Australia, Canada, European Union, India, New Zealand, Singapore, and many other countries in Latin America, the Middle East-Africa region, and Asia Pacific. The lenses have not been withdrawn or recalled from any country for any reason related to safety or effectiveness.

## VIII. POTENTIAL ADVERSE EFFECTS OF THE DEVICE ON HEALTH

Potential complications generally associated with cataract surgery include, but are not limited to: endophthalmitis/intraocular infection, hypopyon, hyphema, IOL dislocation, persistent cystoid macular edema, pupillary block, retinal detachment/tear, persistent corneal stromal edema, persistent uveitis, persistent raised intraocular pressure (IOP) requiring treatment (e.g., AC tap), retained lens material, or toxic anterior segment syndrome, or any other adverse event that leads to permanent visual impairment or requires surgical or medical intervention to prevent permanent visual impairment.

Adverse events that may be associated with use of the device include: IOL dislocation, tilt or decentration, visual symptoms requiring lens removal, residual refractive error, secondary surgical intervention (including IOL repositioning or removal).

For the specific adverse events that occurred during the TECNIS Synergy™ IOL clinical study, please see the Summary of Primary Clinical Studies section below.

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Summary of Safety and Effectiveness Data (SSED)
TECNIS Synergy™ IOLs, Models ZFR00V, DFR00V, ZFW150, ZFW225, ZFW300, ZFW375, DFW150,
DFW225, DFW300 and DFW375

## IX. SUMMARY OF NONCLINICAL STUDIES

Nonclinical studies performed on either parent devices or subject devices demonstrate the
safety and effectiveness of the TECNIS Synergy™ IOLs. The results of these studies are
summarized below.

### A. Laboratory Studies

# Physicochemical Testing

The TECNIS Synergy™ IOLs use the same lens material as the material parent, the
TECNIS OptiBlue 3-Piece IOL, Model ZV9003 (P980040/S035); therefore,
physicochemical and biological data for these associated lenses are deemed applicable to
the subject devices. All physicochemical reports pertaining to the SENSAR violet-light
filtering soft acrylic material were previously submitted to FDA in 2006 as part of the
180-Day PMA Supplement for the material parent TECNIS OptiBlue 3 Piece IOL, Model
ZV9003 (P980040/S035). P980040 served as the parent lens for the aforementioned
submission to which an SSED is available. The physicochemical characterization of the
TECNIS Synergy™ IOL material met the requirements of ISO 11979-5, Ophthalmic
Implants – Intraocular Lenses – Part 5: Biocompatibility and EN ISO 10993-1, Biological
Evaluation of Medical Devices – Part 1: Evaluation and Testing Within a Risk
Management Process. The physicochemical tests are summarized in Table 2. All
acceptance criteria for physicochemical testing were met.

Table 2
Physicochemical Test Summary:
TECNIS Synergy™ IOLs,
Indicating Relationship to the SENSAR® AR40e IOL

|  Physicochemical Tests | Results of Testing  |
| --- | --- |
|  **Exhaustive Extraction** | Equivalent to SENSAR soft acrylic IOL, Model AR40e (P980040)  |
|  **Leachables** | Equivalent to SENSAR soft acrylic IOL, Model AR40e (P980040)  |
|  **Insoluble Inorganics** | No hazardous components identified  |
|  **Hydrolytic Stability** | Stable to 5 years equivalent age  |
|  **Photostability** | Stable to 20 years equivalent age  |
|  **Nd:YAG laser** | Equivalent to SENSAR soft acrylic IOL, Model AR40e (P980040)  |

Note: The SENSAR® AR40e IOL has the OptiEdge design and was approved in the same
PMA (P980040) as the SENSAR® AR40 IOL, which has a rounded optic edge design.

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Summary of Safety and Effectiveness Data (SSED)

TECNIS Synergy™ IOLs, Models ZFR00V, DFR00V, ZFW150, ZFW225, ZFW300, ZFW375, DFW150, DFW225, DFW300 and DFW375

### B. Animal Studies

#### Biological Testing

The TECNIS Synergy™ IOLs are made of the same soft acrylic violet-filtering material and have the same manufacturing contact materials previously qualified with the material parent, the TECNIS OptiBlue 3-Piece IOL, Model ZV9003 (P980040/S035). All physicochemical reports pertaining to the SENSAR® violet-light filtering soft acrylic material was previously submitted to FDA in 2006 as part of the 180-Day PMA Supplement for the material parent TECNIS OptiBlue 3 Piece IOL, Model ZV9003 (P980040/S035). P980040 served as the parent lens for the aforementioned submission to which an SSED is available. The biocompatibility studies were performed in accordance with the requirements in ISO 10993, Biological Evaluation of Medical Devices, and 11979-5 Ophthalmic Implants – Intraocular Lenses – Part 5: Biocompatibility guidelines, to establish a complete profile of the IOL material. The results are summarized in Table 3. All acceptance criteria for biocompatibility were met.

Table 3
Biocompatibility Test Summary:
TECNIS Synergy™ IOL

|  Biological Tests | Results of Testing  |
| --- | --- |
|  Cytotoxicity: (MEM) Agar Diffusion Solid Contact & Saline Extract) | Non-cytotoxic  |
|  Percentage Inhibition of Cell Growth Method | Non-inhibitory to cell growth  |
|  Guinea Pig Maximization a. Saline Extract b. Sesame Oil Extract | Non-sensitizing  |
|  Non-Ocular Implant Study (Six-Week Subcutaneous Implantation in Rabbits) | Passed  |
|  Six-Month Rabbit Intraocular Study | Passed  |
|  Genotoxicity Testing (Salmonella typhimurium and Escherichia coli reverse mutation assay) | Non-genotoxic, non-mutagenic  |
|  Genotoxicity testing (chromosomal aberration assay in Chinese hamster ovary cells) | Non-clastogenic  |
|  Genotoxicity Testing (Mouse Lymphoma Forward Mutation Assay) | Non-mutagenic under short and long exposure conditions  |

### C. Additional Studies

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Summary of Safety and Effectiveness Data (SSED)  
 TECNIS Synergy™ IOLs, Models ZFR00V, DFR00V, ZFW150, ZFW225, ZFW300, ZFW375, DFW150,  
 DFW225, DFW300 and DFW375

### Optical/Mechanical Testing

Dimensional, optical, and mechanical tests were conducted on finished, sterilized, TECNIS Synergy™ IOLs to verify the conformance to applicable sections of ISO 11979-2, Ophthalmic Implants-Intraocular Lenses-Part 2: Optical Properties and Test Methods; ISO 11979-3, Ophthalmic Implants-Intraocular Lenses Part 3: Mechanical Properties and Test Methods; ANSI Z80.30, American National Standard for Ophthalmics: Toric Intraocular Lenses; ANSI Z80.35, American National Standard for Ophthalmics: Extended Depth of Focus Intraocular Lenses; and ANSI Z80.12, American National Standard for Ophthalmics: Multifocal Intraocular Lenses. As part of mechanical assessment, folding and insertion testing was also performed to verify recovery of lens properties (e.g., optical, etc.) following simulated insertion. Here, the TECNIS Synergy™ IOLs passed all predetermined requirements established in the aforementioned standards where applicable and internal product specifications. **Table 4** summarizes the results of the dimensional, optical, and mechanical testing. Testing for the TECNIS Simplicity™ Delivery System was completed on representative lenses and was focused on optical and mechanical testing on attributes that can be impacted by a change in the storage and delivery of the device; specifically, the recovery of properties following simulated surgical manipulation pertinent to the preloaded IOLs, according to testing requirements from ISO 11979-2 and ISO 11979-3. Here, the lenses met the acceptance criteria and met all predetermined requirements established in the aforementioned standards where applicable and internal product specifications. **Table 5** summarizes the results of the recovery of properties following simulated surgical manipulation for the TECNIS Simplicity™ Delivery System.

**Dimensional, Optical and Mechanical Test Results**

|  Requirements | Results  |
| --- | --- |
|  **Optical Requirements**  |   |
|  Diopter power | **Passed**  |
|  Cylinder Power (TECNIS Synergy™ Toric II IOLs only) | **Passed**  |
|  Image quality | **Passed**  |
|  Spectral transmittance | **Passed**  |
|  Axis Orientation Mark(s) (toric TECNIS Synergy™ IOLs only) | **Passed**  |
|  **Mechanical and Dimensional Testing**  |   |
|  Overall Diameter | **Passed**  |

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Summary of Safety and Effectiveness Data (SSED)  
 TECNIS Synergy™ IOLs, Models ZFR00V, DFR00V, ZFW150, ZFW225, ZFW300, ZFW375, DFW150, DFW225, DFW300 and DFW375

|  Requirements | Results  |
| --- | --- |
|  Vault Height | Passed  |
|  Sagitta | Passed  |
|  Clear Optic diameter | Passed  |
|  Optic Body Diameter | Passed  |
|  Axial Displacement in Compression | Passed  |
|  Optic Decentration | Passed  |
|  Optic Tilt | Passed  |
|  Angle of Contact | Passed  |
|  Compression Force and Decay | Passed  |
|  Dynamic Fatigue Durability | Passed  |
|  Surgical Manipulation | Passed  |
|  Surface and Bulk Homogeneity | Passed  |
|  **Recovery of Properties Following Simulated Surgical Manipulation**  |   |
|  Diopter power | Passed  |
|  Cylinder Power (TECNIS Synergy™ Toric II IOLs only) | Passed  |
|  Image quality | Passed  |
|  Axis Orientation Mark(s) (TECNIS Synergy™ Toric II IOLs only) | Passed  |
|  Overall Diameter | Passed  |
|  Sagitta | Passed  |
|  Surface and Bulk Homogeneity | Passed  |

TECNIS Simplicity™ Testing

|  Testing | Results  |
| --- | --- |
|  Dimensional Testing of the IOLs | Passed  |
|  Optical Testing of the IOLs (ISO 11979-2) | Passed  |

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Summary of Safety and Effectiveness Data (SSED)
TECNIS Synergy™ IOLs, Models ZFR00V, DFR00V, ZFW150, ZFW225, ZFW300, ZFW375, DFW150, DFW225, DFW300 and DFW375

|  Testing | Results  |
| --- | --- |
|  Mechanical Testing of the IOLs (ISO 11979-3) | **Passed**  |
|  Functional Testing of the IOLs | **Passed**  |
|  Characterization Testing for IOL Delivery | The lens delivery factors were identified and further characterized to ensure the optimal lens delivery using the TECNIS Simplicity™ Delivery System.  |

Microbiology, Sterilization, and Shelf Life Adoption / Testing

The lens material and platform, geometry, dimensions, manufacturing method, materials and equipment, sterilization method, and packaging materials and configuration of the TECNIS Synergy™ IOLs packaged in the Daisywheel configuration are the same as those of the FDA-approved monofocal IOL, the TECNIS 1-Piece OptiBlue IOL, Model ZCB00V (P980040/S035), as the reference lens models. The TECNIS Synergy™ IOLs in the Daisywheel configuration will be labeled with a 5-year shelf life. Sterilization validations performed for this associated lens model are deemed applicable to the subject lenses and assures a minimum sterility assurance level of 10⁻⁶. A 3-year shelf life was established for the TECNIS Synergy™ IOLs packaged in the TECNIS Simplicity™ Delivery System based on a 3-year shelf life approved by FDA for the TECNIS Simplicity™ Delivery System in P980040/S098. These tests were conducted in accordance with the following standards and United States Pharmacopeia chapters:

- ANSI/AAMI/ISO 11135-1, Sterilization of Healthcare Products – Ethylene Oxide – Part 1: Requirements for Development, Validation, and Routine Control of a Sterilization Process
- ISO 10993-7, Biological evaluation of medical devices – Part 7: Ethylene oxide sterilization residuals
- USP <85>, Bacterial Endotoxins Test
- ISO 11979-6, Ophthalmic Implants – Intraocular Lenses – Part 6: Shelf-life and transport stability.

# X. SUMMARY OF PRIMARY CLINICAL STUDY

The applicant performed a clinical study to establish a reasonable assurance of safety and effectiveness of the TECNIS Synergy™ IOL, Model ZFR00V under IDE #G190057. Data from this clinical study were the basis for the PMA approval decision. A summary of the clinical study is presented below.

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**Summary of Safety and Effectiveness Data (SSED)  
TECNIS Synergy™ IOLs, Models ZFR00V, DFR00V, ZFW150, ZFW225, ZFW300, ZFW375, DFW150,  
DFW225, DFW300 and DFW375**

The TECNIS Synergy™ Toric II IOLs (Models ZFW150, ZFW225, ZFW300, ZFW375) involved imposing the toric feature from the toric design parents (P980040/S039): TECNIS Toric 1-Piece IOL, Models ZCT150, ZCT225, ZCT300 and ZCT400. Since the study for TECNIS Synergy™ IOL Model ZFR00V established safety, and the applicant has approved toric parent IOLs, additional clinical data was not required to support safety and effectiveness of the toric models, as the only difference is in cylinder powers.

### A. Study Design

Subjects were treated between August 13, 2019 and November 26, 2019. The database for this PMA reflected data collected through June 18, 2020 (6-month visit) and included 272 subjects. There were 15 investigational sites.

The study was a prospective, multicenter, bilateral, comparative, three-way masked (Sponsor, subject, and evaluator), randomized, 6-month clinical investigation of the safety and effectiveness of the TECNIS Synergy™ IOL (study lens) compared to the monofocal TECNIS 1-Piece IOL, Model ZCB00 (control lens). Up to 300 subjects were to be enrolled to achieve approximately 270 bilaterally implanted subjects, resulting in approximately 244 evaluable subjects (122 subjects per IOL group) at 6 months. Each site was to implant a minimum of 20 subjects, and no site was to have implanted more than 25% of the enrollment total.

The statistical analyses were frequentist. The purpose of this study was to evaluate the safety and effectiveness of the investigational TECNIS Synergy™ IOL in comparison to a monofocal control IOL. The 6-month postoperative visit was the key analysis time point for all endpoints. Data for other visits were also included in the final analysis.

The clinical hypotheses were that the investigational TECNIS Synergy™ IOL would provide improved distance corrected near visual acuity (DCNVA), as well as decreased spectacle wear compared to the monofocal control, TECNIS 1-Piece IOL, Model ZCB00. The mean monocular best corrected distance visual acuity (BCDVA) of the investigational TECNIS Synergy™ IOL was to be non-inferior to that of the monofocal control IOL Model ZCB00. Complication and adverse event (AE) rates associated with the investigational TECNIS Synergy™ IOL was to be within the rates for posterior chamber IOLs referenced in ISO 119797:2018.

Study sample sizes were based on the ISO 22979 (Technical Report: Ophthalmic implants — Intraocular lenses — Guidance on assessment of the need for clinical investigation of intraocular lens design modifications) requirements for a Level B modification of a parent lens as well as the requirement for contrast sensitivity testing. The minimum requirements

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**Summary of Safety and Effectiveness Data (SSED)**
**TECNIS Synergy™ IOLs, Models ZFR00V, DFR00V, ZFW150, ZFW225, ZFW300, ZFW375, DFW150, DFW225, DFW300 and DFW375**

were 100 evaluable test subjects per IOL group for Level B, and 122 evaluable test subjects per IOL group for contrast sensitivity. The screen failure rate was assumed to be 10%, and the drop-out rate was assumed to be 10%. To achieve approximately 122 evaluable subjects in each IOL group at 6 months postoperative and allowing for screen failures and drop-out, 150 subjects were to be enrolled in each IOL group to achieve approximately 135 bilaterally implanted subjects in each IOL group.

The control was an active alternative treatment [TECNIS 1-Piece IOL, Model ZCB00 (monofocal)], which is a legally marketed alternative with similar indications for use, except that it is not intended to provide improved vision at intermediate and near distances.

1. Clinical Inclusion and Exclusion Criteria

Enrollment in the Clinical Investigation of the Safety and Effectiveness of an Investigational Model of the TECNIS Intraocular Lens (Model ZFR00V) study was limited to subjects who met the following inclusion criteria:

- Minimum 22 years of age
- Bilateral cataracts for which posterior chamber IOL implantation had been planned
- Preoperative BCDVA of 20/40 Snellen or worse with or without a glare source
- Potential for postoperative BCDVA of 20/30 Snellen or better
- Normal corneal topography with a predicted postoperative corneal astigmatism of less than 1.00 D in both eyes including posterior corneal astigmatism (PCA)
- Clear intraocular media other than cataract in each eye
- Availability, willingness, and sufficient cognitive awareness to comply with examination procedures and study visits
- Signed informed consent and HIPAA authorization or equivalent documentation necessary to comply with applicable privacy laws pertaining to medical treatment in the governing countries

Subjects were not permitted to enroll in the Clinical Investigation of the Safety and Effectiveness of an Investigational Model of the TECNIS Intraocular Lens (Model ZFR00V) study if they, or either eye, met any of the following exclusion criteria:

- Prior corneal refractive (laser-assisted in situ keratomileusis, laser-assisted sub-epithelial keratectomy, radial keratotomy, photorefractive keratectomy, etc.) or intraocular surgery, including prophylactic peripheral iridotomies and peripheral laser

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**Summary of Safety and Effectiveness Data (SSED)**  
**TECNIS Synergy™ IOLs, Models ZFR00V, DFR00V, ZFW150, ZFW225, ZFW300, ZFW375, DFW150, DFW225, DFW300 and DFW375**

retinal repairs, or recent ocular trauma or ocular surgery that was not resolved/stable or may have affected visual outcomes or increased risk to the subject.

- • Corneal abnormalities such as stromal, epithelial, or endothelial dystrophies (e.g., any observed guttata) that were predicted to cause visual acuity losses to a level worse than 20/30 Snellen during the study
- • Inability to achieve keratometric stability for contact lens wearers
- • Subjects with diagnosed degenerative visual disorders (e.g., macular degeneration or other retinal disorders) that were predicted to cause visual acuity losses to a level of 20/30 Snellen or worse during the study
- • Subjects with conditions associated with increased risk of zonular rupture, including capsular or zonular abnormalities that may have led to IOL decentration or tilt, such as pseudoexfoliation, trauma, or posterior capsule defects
- • Use of systemic or ocular medications that may, in the opinion of the Investigator, have confounded the outcome or increased the risk to the subject (e.g., poor dilation or a lack of adequate iris structure to perform standard cataract surgery)
- • Acute, chronic, or uncontrolled systemic or ocular disease or illness that, in the opinion of the Investigator, would have increased the operative risk or confounded the outcome(s) of the study (e.g., poorly controlled diabetes, immunocompromised, connective tissue disease, suspected glaucoma, glaucomatous changes in the fundus or visual field, ocular inflammation, etc.).
- • Any known ocular disease or pathology that, in the opinion of the Investigator, may have affected visual acuity, may have required surgical intervention during the course of the study (macular degeneration, cystoid macular edema, diabetic retinopathy, uncontrolled glaucoma, etc.), may have been expected to require retinal laser treatment or other surgical intervention during the course of the study (macular degeneration, cystoid macular edema, diabetic retinopathy, etc.).
- • Subject was pregnant, planned to become pregnant, was lactating, or had another condition associated with the fluctuation of hormones that could have led to refractive changes
- • Concurrent participation or participation within 60 days prior to preoperative visit in any other clinical trial

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Summary of Safety and Effectiveness Data (SSED)  
 TECNIS Synergy™ IOLs, Models ZFR00V, DFR00V, ZFW150, ZFW225, ZFW300, ZFW375, DFW150,  
 DFW225, DFW300 and DFW375

## 2. Follow-up Schedule

All subjects were scheduled to return for follow-up examinations as described in **Table 6**.

**Clinical Study Visit Schedule**

|  VISIT | EYES EVALUATED | EXAM | VISIT WINDOW  |
| --- | --- | --- | --- |
|  1 | Both Eyes | Preoperative Exam | Within 60 days prior to 1^{st} surgery  |
|  2 | First Eye | Operative | 0-60 days after preoperative exam  |
|  3 | First Eye | 1 day | 1-2 days postoperative  |
|  4 | First Eye | 1 week^{a} | 7-14 days postoperative  |
|  5 | Second Eye | Operative^{a} | No more than 30 days after 1^{st} eye surgery  |
|  6 | Second Eye | 1 day | 1-2 days postoperative  |
|  7 | Second Eye | 1 week | 7-14 days postoperative  |
|  8 | Both Eyes | 1 month | 30 - 60 days postoperative from 2^{nd} eye surgery^{b}  |
|  9 | Both Eyes | 6 months | 120 - 180 days postoperative from 2^{nd} eye surgery^{b}  |

Shaded rows indicate study visits where both eyes are evaluated at the same visit

$^{a}$ The 1-week exam for the first eye should have been completed prior to implanting the second eye.

$^{b}$ If for any reason the second eye was not implanted, the first eye was to be examined for the 1-month study visit 37 to 67 days following the first-eye surgery and for the 6-month study visit 127 to 210 days following the first-eye surgery.

Preoperatively and postoperatively, the objective parameters measured during the study are presented in **Table 7**. Adverse events and complications were recorded at all visits. The key timepoints are shown in the tables summarizing safety and effectiveness (Section 3. Clinical Endpoints). Visual acuity testing included uncorrected distance visual acuity (UCDVA), best-corrected distance visual acuity (BCDVA), uncorrected intermediate visual acuity (UCIVA), distance-corrected intermediate visual acuity (DCIVA), uncorrected near visual acuity (UCNVA), and distance-corrected near visual acuity (DCNVA).

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Summary of Safety and Effectiveness Data (SSED)  
 TECNIS Synergy™ IOLs, Models ZFR00V, DFR00V, ZFW150, ZFW225, ZFW300, ZFW375, DFW150, DFW225, DFW300 and DFW375

**Clinical Study Visit Schedule**

|  Examination (shaded lines indicate masked testing) | Preop | Op | 1 day | 1 week | 1 month | 6 months  |
| --- | --- | --- | --- | --- | --- | --- |
|  Informed consent, ocular history, inclusion/exclusion criteria, potential visual acuity, targeted refraction, IOL | X |  |  |  |  |   |
|  Lens power/serial number (masked), operative procedures |  | X |  |  |  |   |
|  Manifest refraction (Snellen preop; ETDRS postop) | X |  |  | X | X | X  |
|  UCDVA – photopic, monocular |  |  | X | X | X | X  |
|  UCDVA – photopic, binocular |  |  |  |  | X | X  |
|  BCDVA – photopic, monocular (Snellen preop; ETDRS | X |  |  | X | X | X  |
|  BCDVA – photopic binocular |  |  |  |  | X | X  |
|  UCIVA – photopic, binocular at 66 cm |  |  |  |  | X | X  |
|  DCIVA – photopic, monocular at 66 cm |  |  |  |  |  | X  |
|  UCNVA – photopic, binocular at 40 cm |  |  |  |  | X | X  |
|  DCNVA – photopic, monocular at 40 cm |  |  |  |  | X | X  |
|  DCNVA – photopic, binocular at 40 cm |  |  |  |  | X | X  |
|  DCNVA – photopic, monocular at 33 cm |  |  |  |  |  | X  |
|  Defocus – distance-corrected, monocular (first eye) |  |  |  |  |  | X  |
|  Defocus – distance-corrected, binocular |  |  |  |  | X |   |
|  Contrast sensitivity – monocular (first eye) |  |  |  |  |  | X  |
|  Contrast sensitivity - binocular |  |  |  |  | X |   |
|  DCNVA – mesopic, monocular at 40 cm |  |  |  |  |  | X  |
|  DCNVA – mesopic, binocular at 40 cm |  |  |  |  |  | X  |
|  Pupil size |  |  |  |  |  | X  |
|  Keratometry | X |  |  |  |  | X  |
|  Intraocular pressure | X |  | X | X | X | X  |
|  Biomicroscopic slit-lamp exam^{a} | X |  | X | X | X | X  |
|  Fundus exam with fundus visualization | X |  |  |  |  | X  |
|  Adverse event assessment |  | X | X | X | X | X  |
|  Ocular medications | X | X | X | X | X | X  |
|  Ocular/visual symptoms (non-directed) | X |  | X | X | X | X  |
|  Subject questionnaires | X |  |  |  | X | X  |

$^{a}$ Includes determination of medical and lens findings/complications.

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### 3. Clinical Endpoints

With regard to safety, the primary and co-primary safety endpoints and success criteria were:

- The rate of secondary surgical interventions (SSIs) related to optical properties of the lens in first eyes of the TECNIS Synergy™ group was analyzed using descriptive statistics and compared to that of the control group.
- All safety and performance endpoint (SPE) AEs, including total SSI, reported among first eyes of the TECNIS Synergy™ group were compared to ISO SPE rates. The success criterion is that the AE rate in the test group is not statistically significantly higher than the ISO SPE rate (ISO 11979-7:2018 safety and performance endpoint rates).
- All other non-SPE AEs were analyzed using descriptive statistics comparing the two IOL groups.
- Rate of monocular BCDVA 20/40 or better among first eyes in the TECNIS Synergy™ group was compared to the ISO SPE rate.

In addition, the secondary safety endpoint was the monocular (first eyes) best-corrected distance contrast sensitivity for the TECNIS Synergy™ group were compared to control (mesopic with and without glare at 1.5, 3.0, 6.0, and 12.0 cpd and photopic with glare at 3.0, 6.0, 12.0, and 18.0 cpd).

With regard to effectiveness, the primary effectiveness endpoint was monocular photopic DCNVA at 40 cm. Success criteria were a statistically significant improvement in mean monocular photopic DCNVA for first eyes in the TECNIS Synergy™ group vs. first eyes in the control group and a mean DCNVA for the TECNIS Synergy™ group of at least 0.2 logarithm of the minimum angle of resolution (LogMAR).

The secondary effectiveness endpoints included statistically and clinically significant improvements in mean LogMAR distance corrected intermediate visual acuity (DCIVA) at 66 cm and DCNVA at 33 cm for first eyes in the TECNIS Synergy™ group vs. the control, with a mean of at least 0.2 LogMAR. Other secondary effectiveness endpoints included non-inferior (within 0.1 LogMAR) monocular photopic BCDVA for first eyes in the TECNIS Synergy™ group vs. the control, monocular distance-corrected defocus curve for first eyes in the TECNIS Synergy™ group demonstrating 0.2 LogMAR or better from 0.0 D to -2.5 D of defocus, and a statistically significant difference in the proportion of Synergy™ compared to control subjects who reported wearing glasses “None of the time” for all four conditions (distance, intermediate, near, and overall vision), as determined from the Patient Reported Spectacle Independence Questionnaire. In addition, clinical significance was determined by:

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Summary of Safety and Effectiveness Data (SSED)
TECNIS Synergy™ IOLs, Models ZFR00V, DFR00V, ZFW150, ZFW225, ZFW300, ZFW375, DFW150, DFW225, DFW300 and DFW375

1) At least 50% of subjects in the Synergy™ group who reported wearing glasses “None of the time” for all four conditions (distance, intermediate, near, and overall vision), and
2) The proportion of subjects in the Synergy™ group who reported wearing glasses or contacts “None of the time” for all four conditions was at least 25 percentage points higher than that for the control group.

**B. Accountability of PMA Cohort**

At the time of database lock, of 297 patients enrolled in the PMA study, (89.9% (267/297) patients are available for analysis at the completion of the study at the 6-month post-operative visit.

Of the 272 subjects implanted, 135 were in the Synergy™ group, and 137 were in the control group; all 272 subjects were bilaterally implanted with the same IOL model in both eyes in the PMA study. At the time of database lock, 97.0% (131/135) of Synergy™ first eyes (Table 8), and 95.6% (131/137) of control first eyes (Table 9) were available for analysis at the 6-month final study exam.

Table 8
Accountability
First Eyes – TECNIS Synergy™
N = 135

|  Subject status | 1 Day |   | 1 Week |   | 1 Month |   | 6 Months  |   |
| --- | --- | --- | --- | --- | --- | --- | --- | --- |
|   |  n | % | n | % | n | % | n | %  |
|  **Available for Analysis** | 135 | 100.0 | 135 | 100.0 | 135 | 100.0 | 131 | 97.0  |
|  **Missing Subjects** | 0 | 0.0 | 0 | 0.0 | 0 | 0.0 | 4 | 3.0  |
|  o Discontinued | 0 | 0.0 | 0 | 0.0 | 0 | 0.0 | 1 | 0.7  |
|  o Missed visit | 0 | 0.0 | 0 | 0.0 | 0 | 0.0 | 0 | 0.0  |
|  o Not seen but accounted for | 0 | 0.0 | 0 | 0.0 | 0 | 0.0 | 2 | 1.5  |
|  o Lost-to-follow-up | 0 | 0.0 | 0 | 0.0 | 0 | 0.0 | 1 | 0.7  |
|  **Active** | 0 | 0.0 | 0 | 0.0 | 0 | 0.0 | 0 | 0.0  |
|  **Percent Accountability** | - | 100.0 | - | 100.0 | - | 100.0 | - | 97.8  |

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Summary of Safety and Effectiveness Data (SSED)  
 TECNIS Synergy™ IOLs, Models ZFR00V, DFR00V, ZFW150, ZFW225, ZFW300, ZFW375, DFW150, DFW225, DFW300 and DFW375

**First Eyes – TECNIS monofocal**

|  Subject status | 1 Day |   | 1 Week |   | 1 Month |   | 6 Months  |   |
| --- | --- | --- | --- | --- | --- | --- | --- | --- |
|   |  n | % | n | % | n | % | n | %  |
|  **Available for Analysis** | 137 | 100.0 | 137 | 100.0 | 136 | 99.3 | 131 | 95.6  |
|  **Missing Subjects** | 0 | 0.0 | 0 | 0.0 | 1 | 0.7 | 6 | 4.4  |
|  o Discontinued | 0 | 0.0 | 0 | 0.0 | 0 | 0.0 | 0 | 0.0  |
|  o Missed visit | 0 | 0.0 | 0 | 0.0 | 0 | 0.0 | 0 | 0.0  |
|  o Not seen but accounted for | 0 | 0.0 | 0 | 0.0 | 1^{b} | 0.7 | 5 | 3.6  |
|  o Lost-to-follow-up | 0 | 0.0 | 0 | 0.0 | 0 | 0.0 | 1 | 0.7  |
|  **Active** | 0 | 0.0 | 0 | 0.0 | 0 | 0.0 | 0 | 0.0  |
|  **Percent Accountability** | - | 100.0 | - | 100.0 | - | 99.3 | - | 95.6  |

### C. Study Population Demographics and Baseline Parameters

The demographics of the study population are typical for a randomized, prospective, multicenter clinical study performed in the US.

**Table 10** presents demographic information for Synergy™ and control subjects. The mean age was 68.5 years (standard deviation (SD) 7.1) in the Synergy™ group and 68.5 years (SD 7.7) in the control group. Female subjects comprised more than half of both the Synergy™ group (69.6%; 94/135) and the control group (65.7%; 90/137). No statistically significant differences were found for age, sex, race, ethnicity, or iris color between the two IOL groups.

**Table 11** presents the preoperative parameters for Synergy™ and control subjects. The differences in the means between IOL groups were very small for preoperative intended mean refractive spherical equivalent (MRSE) (difference of 0.036 D first eyes and 0.068 D second eyes), preoperative keratometric cylinder (difference of -0.019 D first eyes and -0.030 D second eyes), and the IOL power implanted (difference of 0.361 D first eyes and 0.361 D second eyes).

**Synergy™ and Control Subjects**

|   |  | TECNIS Synergy™ | TECNIS monofocal | P-Value  |
| --- | --- | --- | --- | --- |
|  Age (years) | N | 135 | 137 | 0.9940^{a}  |
|   |  Mean | 68.5 | 68.5  |   |

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# **Summary of Safety and Effectiveness Data (SSED)**  
 **TECNIS Synergy™ IOLs, Models ZFR00V, DFR00V, ZFW150, ZFW225, ZFW300, ZFW375, DFW150, DFW225, DFW300 and DFW375**

|   |   | TECNIS Synergy™ |   | TECNIS monofocal |   | P-Value  |
| --- | --- | --- | --- | --- | --- | --- |
|   | SD | 7.1 |   | 7.7 |   |   |
|   | Median | 70 |   | 69 |   |   |
|   | Min | 48 |   | 46 |   |   |
|   | Max | 85 |   | 92 |   |   |
|   | Not Reported | 0 |   | 0 |   |   |
|   |  | **n** | **%** | **n** | **%** |   |
|  Age Group | <60 | 17 | (12.6%) | 17 | (12.4%) |   |
|   |  60 to 69 | 50 | (37.0%) | 57 | (41.6%) |   |
|   |  70 to 79 | 62 | (45.9%) | 56 | (40.9%) |   |
|   |  ≥80 | 6 | (4.4%) | 7 | (5.1%) |   |
|   |  Total n | 135 | - | 137 | - |   |
|   |  Not Reported | 0 | - | 0 | - |   |
|  Sex | Male | 41 | (30.4%) | 47 | (34.3%) | 0.5185^{b}  |
|   |  Female | 94 | (69.6%) | 90 | (65.7%)  |   |
|   |  Total n | 135 | - | 137 | -  |   |
|   |  Not Reported | 0 | - | 0 | -  |   |
|  Race | Asian (including Indian) | 3 | (2.2%) | 1 | (0.7%) | 0.6200^{b}  |
|   |  Black | 15 | (11.1%) | 19 | (13.9%)  |   |
|   |  Native Hawaiian/Pacific Islander | 1 | (0.7%) | 0 | (0.0%)  |   |
|   |  Caucasian | 114 | (84.4%) | 116 | (84.7%)  |   |
|   |  Other Race | 2 | (1.5%) | 1 | (0.7%)  |   |
|   |  Total n | 135 | - | 137 | -  |   |
|   |  Not Reported | 0 | - | 0 | -  |   |
|  Ethnicity | Hispanic/Latino | 8 | (5.9%) | 7 | (5.1%) | 0.7969^{b}  |
|   |  Not Hispanic/Latino | 127 | (94.1%) | 130 | (94.9%)  |   |
|   |  Total n | 135 | - | 137 | -  |   |
|   |  Not Reported | 0 | - | 0 | -  |   |
|  Iris Color | Blue/Gray | 42 | (31.1%) | 37 | (27.0%) | 0.6008^{b}  |
|   |  Brown/Black | 54 | (40.0%) | 63 | (46.0%)  |   |
|   |  Green/Hazel | 39 | (28.9%) | 37 | (27.0%)  |   |
|   |  Total n | 135 | - | 137 | -  |   |
|   |  Not Reported | 0 | - | 0 | -  |   |

%=n/Total n

$^{a}$ P-value from two-sided two sample t-test

$^{b}$ P-value from two-sided Fisher's exact test

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Summary of Safety and Effectiveness Data (SSED)
TECNIS Synergy™ IOLs, Models ZFR00V, DFR00V, ZFW150, ZFW225, ZFW300, ZFW375, DFW150, DFW225, DFW300 and DFW375

Table 11
Mean Intended MRSE and Preoperative Keratometric Cylinder
First Eyes – TECNIS Synergy™ (N=135) and TECNIS monofocal (N=137)

|  Variable | IOL | n | Standard  |   |   |   |   |
| --- | --- | --- | --- | --- | --- | --- | --- |
|   |   |   |  Mean | Deviation | Median | Minimum | Maximum  |
|  Intended MRSE (D) | ZFR00V | 135 | -0.009 | 0.097 | -0.010 | -0.24 | 0.19  |
|   |  Control | 137 | -0.045 | 0.114 | -0.050 | -0.35 | 0.22  |
|   |  Difference | - | 0.036 | 0.106 | - | - | -  |
|  Keratometric Cylinder (D) | ZFR00V | 135 | 0.473 | 0.247 | 0.460 | 0.00 | 1.13  |
|   |  Control | 137 | 0.492 | 0.241 | 0.470 | 0.00 | 1.31  |
|   |  Difference | - | -0.019 | 0.244 | - | - | -  |

## D. Safety and Effectiveness Results

1. Safety Results

The analysis of safety was based on the safety cohort of 135 subjects with Synergy™ bilaterally and 137 subjects with control bilaterally and available for the 6-month evaluation.

The first co-primary safety endpoint was the rate of secondary surgical interventions (SSIs) related to the optical properties of the IOL in first operative eyes. One SSI related to the optical properties of the IOL was reported in the clinical study among all implanted eyes in the Synergy™ group. The second co-primary safety endpoint was the rates of cumulative and persistent adverse events in first operative eyes at 6 Months in comparison to ISO 11979-7 Safety and Performance Endpoints grid (SPE rates). All SPE rates for the Synergy™ group at 6 months were below those specified in ISO 11979-7:2018 (12-month rates).

The third co-primary safety endpoint was the rate of all non-SPE adverse events in the study. The fourth co-primary safety endpoint was met, where the rate of monocular BCDVA 20/40 or better among first eyes was better than the rate specified in ISO 11979-7:2018.

Secondary safety endpoints included assessments of monocular and binocular contrast sensitivity with and without glare for photopic and mesopic conditions. Log contrast sensitivity was measured to be lower for the Synergy™ group than control at higher spatial frequencies, however the differences were not clinically meaningful.

The key safety outcomes for this study are presented below in Tables 12 to 16 (adverse effects) and Figures 4-9 (contrast sensitivity).

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Summary of Safety and Effectiveness Data (SSED)
TECNIS Synergy™ IOLs, Models ZFR00V, DFR00V, ZFW150, ZFW225, ZFW300, ZFW375, DFW150, DFW225, DFW300 and DFW375

**Adverse effects that occurred in the PMA clinical study:**

During the study, reports of serious adverse events (SAEs) and serious adverse device effects (SADEs) were low for both lens groups. None of the events reported were unanticipated. One Synergy™ subject had lens decentration (1/135, 0.7%) in both eyes.

**Table 12** presents the incidence of serious and non-serious medical findings/adverse events at 6-months for all Synergy™ and monofocal control eyes.

Among first and second eyes with the TECNIS Synergy™ IOL, ocular AEs occurring at 6 months with a rate of 2% or more were: posterior capsule opacification (116/263; 44.1%), posterior vitreous detachment (76/263; 28.9%), dermatochalasis (56/263; 21.3%), dry eye/superficial punctate keratopathy/epithelial erosion/tear film insufficiency (50/263; 19.0%), blepharitis/meibomianitis (40/263; 15.2%), posterior capsular striae/wrinkles (16/263; 6.1%), pinguecula (14/263; 5.3%), periorbital fat herniation (14/263; 5.3%), and ptosis (6/263; 2.3%).

Among first and second eyes with the control IOL, ocular AEs occurring at 6 months with a rate of 2% or more were: posterior capsule opacification (106/262; 40.5%), posterior vitreous detachment (76/262; 29.0%), dermatochalasis (49/262, 18.7%), dry eye/superficial punctate keratopathy/epithelial erosion/tear film insufficiency (46/262; 17.6%), blepharitis/meibomianitis (48/262; 18.3%), pinguecula (15/262; 5.7%), posterior capsular striae/wrinkles (10/262; 3.8%), periorbital fat herniation (10/262; 3.8%), arcus (9/262; 3.4%), and corneal scar (6/262; 2.3%).

**Table 12**
**Medical Findings/Adverse Events at 6 Months**
**TECNIS Synergy™ and TECNIS Monofocal**
**Pooled (First and Second) Eyes**
**Safety Population**

|  Medical Findings | TECNIS Synergy N=263 |   | TECNIS Monofocal N=262  |   |
| --- | --- | --- | --- | --- |
|   |  n | % | n | %  |
|  Posterior capsule opacification (any) | 116 | 44.1 | 106 | 40.5  |
|  Posterior vitreous detachment | 76 | 28.9 | 76 | 29.0  |
|  Dermatochalasis | 56 | 21.3 | 49 | 18.7  |
|  Dry eye/superficial punctate keratopathy/epithelial erosion/tear film insufficiency | 50 | 19.0 | 46 | 17.6  |
|  Blepharitis/meibomianitis | 40 | 15.2 | 48 | 18.3  |
|  Posterior capsular striae/wrinkles (any) | 16 | 6.1 | 10 | 3.8  |
|  Periorbital fat herniation | 14 | 5.3 | 10 | 3.8  |

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# **Summary of Safety and Effectiveness Data (SSED)**

**TECNIS Synergy™ IOLs, Models ZFR00V, DFR00V, ZFW150, ZFW225, ZFW300, ZFW375, DFW150, DFW225, DFW300 and DFW375**

|  Medical Findings | TECNIS Synergy N=263 |   | TECNIS Monofocal N=262  |   |
| --- | --- | --- | --- | --- |
|   |  n | % | n | %  |
|  Pinguecula | 14 | 5.3 | 15 | 5.7  |
|  Ptosis | 6 | 2.3 | 4 | 1.5  |
|  Chorioretinal atrophy | 5 | 1.9 | 5 | 1.9  |
|  Congenital optic nerve anomaly | 5 | 1.9 | 0 | 0.0  |
|  Epiretinal membrane | 5 | 1.9 | 1 | 0.4  |
|  Corneal dystrophy | 4 | 1.5 | 4 | 1.5  |
|  Drusen | 4 | 1.5 | 5 | 1.9  |
|  Eye nevus | 4 | 1.5 | 1 | 0.4  |
|  Guttata | 4 | 1.5 | 2 | 0.8  |
|  Corneal scar | 3 | 1.1 | 6 | 2.3  |
|  Optic nerve cup/disc ratio increased | 3 | 1.1 | 0 | 0.0  |
|  Pterygium | 3 | 1.1 | 2 | 0.8  |
|  Retinal degeneration | 3 | 1.1 | 0 | 0.0  |
|  Retinal pigment epithelium (RPE) changes | 3 | 1.1 | 2 | 0.8  |
|  Arcus | 2 | 0.8 | 9 | 3.4  |
|  Conjunctival hyperemia/injection | 2 | 0.8 | 0 | 0.0  |
|  Conjunctivitis | 2 | 0.8 | 0 | 0.0  |
|  Conjunctivochalasis | 2 | 0.8 | 0 | 0.0  |
|  Corneal disorder | 2 | 0.8 | 0 | 0.0  |
|  Corneal pigmentation^{b} | 2 | 0.8 | 2 | 0.8  |
|  Heterophoria | 2 | 0.8 | 0 | 0.0  |
|  Macular degeneration | 2 | 0.8 | 0 | 0.0  |
|  Optic nerve cupping | 2 | 0.8 | 0 | 0.0  |
|  Optic nerve hypoplasia | 2 | 0.8 | 0 | 0.0  |
|  Telangiectasia | 2 | 0.8 | 0 | 0.0  |
|  Anterior chamber cells (if any) | 1 | 0.4 | 4 | 1.5  |
|  Chorioretinal scar | 1 | 0.4 | 1 | 0.4  |
|  Corneal opacity | 1 | 0.4 | 1 | 0.4  |
|  Eyelid cyst | 1 | 0.4 | 2 | 0.8  |
|  Lagophthalmos | 1 | 0.4 | 0 | 0.0  |
|  Macular hole | 1 | 0.4 | 0 | 0.0  |
|  Retinal anomaly congenital | 1 | 0.4 | 1 | 0.4  |
|  Retinal scar | 1 | 0.4 | 0 | 0.0  |
|  Vitreous degeneration | 1 | 0.4 | 0 | 0.0  |
|  Anterior chamber flare (if any) | 0 | 0.0 | 3 | 1.1  |
|  Cornea verticillata | 0 | 0.0 | 2 | 0.8  |
|  Corneal edema (if any)^{b} | 0 | 0.0 | 2 | 0.8  |

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Summary of Safety and Effectiveness Data (SSED)  
 TECNIS Synergy™ IOLs, Models ZFR00V, DFR00V, ZFW150, ZFW225, ZFW300, ZFW375, DFW150, DFW225, DFW300 and DFW375

|  Medical Findings | TECNIS Synergy N=263 |   | TECNIS Monofocal N=262  |   |
| --- | --- | --- | --- | --- |
|   |  n | % | n | %  |
|  Iris transillumination defect^{b} | 0 | 0.0 | 2 | 0.8  |
|  Madarosis | 0 | 0.0 | 2 | 0.8  |
|  Presumed ocular histoplasmosis syndrome | 0 | 0.0 | 2 | 0.8  |
|  Retinal hemorrhage | 0 | 0.0 | 2 | 0.8  |
|  Elevated IOP/ocular hypertension^{b} | 0 | 0.0 | 1 | 0.4  |
|  Hyalosis asteroid | 0 | 0.0 | 1 | 0.4  |
|  Retinal exudates | 0 | 0.0 | 1 | 0.4  |
|  Retinal tear^{b} | 0 | 0.0 | 1 | 0.4  |
|  Strabismus | 0 | 0.0 | 1 | 0.4  |
|  Other | 0 | 0.0 | 2^{a} | 0.8^{a}  |

$^{a}$ Other includes orbital fat prolapse and negative dysphotopsia.

$^{b}$ As defined by AAO IOL Task Force (Masket *et al.*, 2016).

The incidence rates of persistent (**Table 13**) and cumulative (**Table 14**) adverse events for all implanted Synergy™ eyes were compared to the ISO SPE (safety and performance endpoint) rates. There were no persistent medical findings/adverse events per the ISO SPE at 6 months in the Synergy™ group. The rate of cumulative medical findings/adverse events reported in Synergy™ group were not statistically significantly higher than the specified ISO SPE rates.

All SSIs during the study are presented by IOL group in **Table 15**. Five SAEs/SADEs required SSIs for treatment: one first eye (0.7%, 1/135 for Synergy™ vs. 0%, 0/137 for control) and four second eyes (2.2%, 3/135 for Synergy™ vs. 0.7%, 1/137 for control). There was one (0.7%, 1/135) SSI related to optical properties of the lens in the Synergy™ group.

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Summary of Safety and Effectiveness Data (SSED)
TECNIS Synergy™ IOLs, Models ZFR00V, DFR00V, ZFW150, ZFW225, ZFW300, ZFW375, DFW150, DFW225, DFW300 and DFW375

Table 13
6-Month Persistent Adverse Events vs. ISO 11979-7 SPE 12-Month Rates
TECNIS Synergy™

|  Persistent Medical Complication/Adverse Event | ISO SPE Rate % | First Eyes N=131 |   | Second Eyes N=132  |   |
| --- | --- | --- | --- | --- | --- |
|   |   |  n | % | n | %  |
|  Corneal edema | 0.3 | 0 | 0.0 | 0 | 0.0  |
|  Cystoid macular edema | 0.5 | 0 | 0.0 | 0 | 0.0  |
|  Iritis | 0.3 | 0 | 0.0 | 0 | 0.0  |
|  Raised IOP requiring treatment | 0.4 | 0 | 0.0 | 0 | 0.0  |

Table 14
6-Month Cumulative Adverse Events vs. ISO 11979-7 SPE 12-Month Rates
TECNIS Synergy™

|  Cumulative Medical Complication/ Adverse Event | ISO SPE Rate % | First Eyes N=135 |   | Second Eyes N=135  |   |
| --- | --- | --- | --- | --- | --- |
|   |   |  n | % | n | %  |
|  Cystoid macular edema | 3.0 | 1 | 0.7 | 1 | 0.7  |
|  Hypopyon^{a} | 0.3 | 0 | 0.0 | 1 | 0.7*  |
|  Endophthalmitis | 0.1 | 0 | 0.0 | 0 | 0.0  |
|  Lens dislocated from posterior chamber | 0.1 | 0 | 0.0 | 0 | 0.0  |
|  Pupillary block | 0.1 | 0 | 0.0 | 0 | 0.0  |
|  Retinal detachment | 0.3 | 0 | 0.0 | 0 | 0.0  |
|  Eyes with secondary surgical intervention | 0.8 | 1 | 0.7 | 3 | 2.2*  |
|  -- Device related | - | 1 | 0.7 | 1 | 0.7  |
|  -- Not device related | - | 0 | 0.0 | 2 | 1.5*  |

% = (n/N) *100

* Rate is not statistically significantly higher than ISO SPE rate (p>0.05).

$^{a}$Associated with a single report of toxic anterior segment syndrome (TASS), which occurred in same eye.

Table 15
Secondary Surgical Interventions by IOL Group

|  Secondary Surgical Interventions (SSIs) | TECNIS Synergy™ |   |   |   | TECNIS monofocal  |   |   |   |
| --- | --- | --- | --- | --- | --- | --- | --- | --- |
|   |  First Eyes N=135 |   | Second Eyes N=135 |   | First Eyes N=137 |   | Second Eyes N=137  |   |
|   |  n | % | n | % | n | % | n | %  |
|  |   |   |   |   |   |   |   |   |

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# **Summary of Safety and Effectiveness Data (SSED)**  
 **TECNIS Synergy™ IOLs, Models ZFR00V, DFR00V, ZFW150, ZFW225, ZFW300, ZFW375, DFW150, DFW225, DFW300 and DFW375**

|   | TECNIS Synergy™ |   |   |   | TECNIS monofocal  |   |   |   |
| --- | --- | --- | --- | --- | --- | --- | --- | --- |
|   |  First Eyes N=135 |   | Second Eyes N=135 |   | First Eyes N=137 |   | Second Eyes N=137  |   |
|   |  n | % | n | % | n | % | n | %  |
|  -- Lens Removal | 1^{a} | 0.7 | 0 | 0.0 | 0 | 0.0 | 0 | 0.0  |
|  -- Aspiration (Removal) of Lens Fragments | 0 | 0.0 | 1^{b} | 0.7 | 0 | 0.0 | 0 | 0.0  |
|  -- Retinal Repair | 0 | 0.0 | 1^{c} | 0.7 | 0 | 0.0 | 1^{c} | 0.7  |
|  -- Treatment Injection | 0 | 0.0 | 1^{d} | 0.7 | 0 | 0.0 | 0 | 0.0  |
|  **TOTAL Eyes with SSIs** | **1** | **0.7** | **3** | **2.2** | **0** | **0.0** | **1** | **0.7**  |

% = (n/N) *100

$^{a}$SSI related to visual symptoms (optical properties of the lens). The second eye lens for same subject was removed after study exit for similar reason.

$^{b}$Due to retained lens material

$^{c}$Due to macular hole

$^{d}$Due to hypopyon and TASS in same eye

$^{e}$Due to retinal detachment/tear

## Contrast Sensitivity

Monocular best-corrected distance contrast sensitivity was evaluated under three lighting conditions: mesopic without glare, mesopic with glare, and photopic with glare. The secondary safety endpoint was a comparison of the median monocular and binocular contrast sensitivity measurements at all spatial frequencies and all lighting conditions at 6 months. In all conditions, contrast sensitivity was measured to be generally lower for the Synergy™ group than the control group (**Figures 4, 5, and 6**), especially under extremely high glare conditions. Glare setting used for testing was high enough to reduce the mesopic contrast sensitivity in both lens groups by at least 0.2 log units with a greater impact on mesopic contrast sensitivity for the Synergy™ group (up to 0.448 log) than the control group (up to 0.392 log). However, lower contrast sensitivity measurements were not found to be associated with clinically significant impact to patient reported vision quality. In addition, median binocular contrast sensitivity measurements at all spatial frequencies and all lighting conditions at 1 month are presented in **Figures 7, 8, and 9**.

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Summary of Safety and Effectiveness Data (SSED)
TECNIS Synergy™ IOLs, Models ZFR00V, DFR00V, ZFW150, ZFW225, ZFW300, ZFW375, DFW150, DFW225, DFW300 and DFW375

Figure 2
Monocular Best-Corrected Distance Contrast Sensitivity at 6 Months
Mesopic Without Glare
Medians with 5th and 95th Percentile Error Bars

![img-5.jpeg](img-5.jpeg)

Figure 3
Monocular Best-Corrected Distance Contrast Sensitivity at 6 Months
Mesopic With Glare
Medians with 5th and 95th Percentile Error Bars

![img-6.jpeg](img-6.jpeg)

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Summary of Safety and Effectiveness Data (SSED)
TECNIS Synergy™ IOLs, Models ZFR00V, DFR00V, ZFW150, ZFW225, ZFW300, ZFW375, DFW150, DFW225, DFW300 and DFW375

Figure 4
Monocular Best-Corrected Distance Contrast Sensitivity at 6 Months
Photopic With Glare
Medians with 5th and 95th Percentile Error Bars

![img-7.jpeg](img-7.jpeg)

Figure 5
Binocular Best-Corrected Distance Contrast Sensitivity at 1 Month
Mesopic without Glare
Medians with 5th and 95th Percentile Error Bars

![img-8.jpeg](img-8.jpeg)

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Summary of Safety and Effectiveness Data (SSED)
TECNIS Synergy™ IOLs, Models ZFR00V, DFR00V, ZFW150, ZFW225, ZFW300, ZFW375, DFW150, DFW225, DFW300 and DFW375

Figure 6
Binocular Best-Corrected Distance Contrast Sensitivity at 1 Month
Mesopic with Glare
Medians with 5th and 95th Percentile Error Bars

![img-9.jpeg](img-9.jpeg)

Figure 7
Binocular Best-Corrected Distance Contrast Sensitivity at 1 Month
Photopic with Glare
Medians with 5th and 95th Percentile Error Bars

![img-10.jpeg](img-10.jpeg)

### Optical/Visual Symptoms

Optical/visual symptoms that were spontaneously reported by subjects (non-directed) and questionnaire-directed reports of experience/bother/difficulty with visual problems (directed) were evaluated. Non-directed reports of optical/visual symptoms included halos, night glare, and starbursts, of which there were few reports of severe symptoms for both Synergy and control groups (Table 16). As shown in the responses to the directed questionnaire (Table 17), reports of

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# **Summary of Safety and Effectiveness Data (SSED)**

**TECNIS Synergy™ IOLs, Models ZFR00V, DFR00V, ZFW150, ZFW225, ZFW300, ZFW375, DFW150, DFW225, DFW300 and DFW375**

bothersome visual disturbances were generally acceptable for the Synergy group at 6 months. The highest rate of the most bothersome reports (“extremely bothersome”) of optical/visual symptoms at 6 months was for starbursts, at 5.3% (7/131) for Synergy and 0.0% (0/131) for the control.

Bother or difficulty with a visual symptom that interfered with a daily activity for more than 3 months and was considered by the investigator to be at least possibly related to the IOL was considered an Adverse Device Effect. There were eleven such events from 8.1% (11/135) of Synergy™ subjects and none for control subjects; one resulted in lens removal.

**Spontaneous (Non-directed$^{a}$) Reports of Optical/Visual Symptoms (First Eyes) at 6 Months**

|   | TECNIS Synergy N=131 |   | TECNIS monofocal N=131  |   |
| --- | --- | --- | --- | --- |
|   |  n | % | n | %  |
|  Halos^{b} | 30 | 22.9 | 5 | 3.8  |
|  oMild | 8 | 6.1 | 3 | 2.3  |
|  oModerate | 17 | 13.0 | 2 | 1.5  |
|  oSevere | 5 | 3.8 | 0 | 0.0  |
|  Night Glare^{b} | 11 | 8.4 | 2 | 1.5  |
|  oMild | 1 | 0.8 | 0 | 0.0  |
|  oModerate | 7 | 5.3 | 2 | 1.5  |
|  oSevere | 3 | 2.3 | 0 | 0.0  |
|  Starbursts^{b} | 13 | 9.9 | 2 | 1.5  |
|  oMild | 3 | 2.3 | 2 | 1.5  |
|  oModerate | 5 | 3.8 | 0 | 0.0  |
|  oSevere | 5 | 3.8 | 0 | 0.0  |
|  Photophobia | 2 | 1.5 | 3 | 2.3  |
|  Day glare | 2 | 1.5 | 1 | 0.8  |
|  Night vision difficulty | 6 | 4.6 | 1 | 0.8  |

% = (n/N)*100

Subjects may report multiple symptoms.

$^{a}$Responses to the question, “Are you having any difficulties with your eyes or vision?”

$^{b}$Severity collected in follow-up response

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Summary of Safety and Effectiveness Data (SSED)  
 TECNIS Synergy™ IOLs, Models ZFR00V, DFR00V, ZFW150, ZFW225, ZFW300, ZFW375, DFW150, DFW225, DFW300 and DFW375

**Experience/Bother With Visual Symptoms at 6 Months (Directed Questionnaire)**

|   |   | TECNIS Synergy™ N=131 |   | TECNIS monofocal N=131  |   |
| --- | --- | --- | --- | --- | --- |
|   |   | n | % | n | %  |
|  **Halos** | Did not experience or NR | 24 | 18.3 | 79 | 60.3  |
|   |  Not at all bothered | 19 | 14.5 | 23 | 17.6  |
|   |  Slightly bothered | 40 | 30.5 | 22 | 16.8  |
|   |  Moderately bothered | 30 | 22.9 | 6 | 4.6  |
|   |  Very bothered | 13 | 9.9 | 1 | 0.8  |
|   |  Extremely bothered | 5 | 3.8 | 0 | 0.0  |
|  **Starbursts** | Did not experience or NR | 46 | 35.1 | 102 | 77.9  |
|   |  Not at all bothered | 18 | 13.7 | 17 | 13.0  |
|   |  Slightly bothered | 27 | 20.6 | 4 | 3.1  |
|   |  Moderately bothered | 25 | 19.1 | 6 | 4.6  |
|   |  Very bothered | 8 | 6.1 | 2 | 1.5  |
|   |  Extremely bothered | 7 | 5.3 | 0 | 0.0  |
|  **Multiple or Double Vision** | Did not experience or NR | 113 | 86.3 | 116 | 88.5  |
|   |  Not at all bothered | 2 | 1.5 | 5 | 3.8  |
|   |  Slightly bothered | 10 | 7.6 | 4 | 3.1  |
|   |  Moderately bothered | 2 | 1.5 | 5 | 3.8  |
|   |  Very bothered | 2 | 1.5 | 1 | 0.8  |
|   |  Extremely bothered | 2 | 1.5 | 0 | 0.0  |
|  **Sensitivity to Light** | Did not experience or NR | 63 | 48.1 | 71 | 54.2  |
|   |  Not at all bothered | 13 | 9.9 | 9 | 6.9  |
|   |  Slightly bothered | 30 | 22.9 | 32 | 24.4  |
|   |  Moderately bothered | 19 | 14.5 | 11 | 8.4  |
|   |  Very bothered | 5 | 3.8 | 6 | 4.6  |
|   |  Extremely bothered | 1 | 0.8 | 2 | 1.5  |
|  **Glare Related to Scattered Light** | Did not experience or NR | 69 | 52.7 | 110 | 84.0  |
|   |  Not at all bothered | 9 | 6.9 | 4 | 3.1  |
|   |  Slightly bothered | 23 | 17.6 | 12 | 9.2  |
|   |  Moderately bothered | 19 | 14.5 | 3 | 2.3  |
|   |  Very bothered | 5 | 3.8 | 2 | 1.5  |
|   |  Extremely bothered | 6 | 4.6 | 0 | 0.0  |
|  **Occlusions** | Did not experience or NR | 127 | 96.9 | 128 | 97.7  |
|   |  Not at all bothered | 1 | 0.8 | 1 | 0.8  |
|   |  Slightly bothered | 1 | 0.8 | 2 | 1.5  |
|   |  Moderately bothered | 0 | 0.0 | 0 | 0.0  |

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Summary of Safety and Effectiveness Data (SSED)  
 TECNIS Synergy™ IOLs, Models ZFR00V, DFR00V, ZFW150, ZFW225, ZFW300, ZFW375, DFW150, DFW225, DFW300 and DFW375

|   |   | TECNIS Synergy™ N=131 |   | TECNIS monofocal N=131  |   |
| --- | --- | --- | --- | --- | --- |
|   |   | n | % | n | %  |
|   | Very bothered | 2 | 1.5 | 0 | 0.0  |
|   |  Extremely bothered | 0 | 0.0 | 0 | 0.0  |
|  **Poor Low Light Vision** | Did not experience or NR | 79 | 60.3 | 80 | 61.1  |
|   |  Not at all bothered | 9 | 6.9 | 6 | 4.6  |
|   |  Slightly bothered | 25 | 19.1 | 34 | 26.0  |
|   |  Moderately bothered | 15 | 11.5 | 6 | 4.6  |
|   |  Very bothered | 3 | 2.3 | 4 | 3.1  |
|   |  Extremely bothered | 0 | 0.0 | 1 | 0.8  |

% = (n/N)*100

NR = Not Reported

## 2. Effectiveness Results

Effectiveness analyses were based on the modified intent-to-treat (mITT) cohort of 135 subjects with bilateral Synergy™ lenses and 137 subjects with bilateral control lenses who were available for the 6-month evaluation. For determination of endpoint criteria, statistical significance was assessed using the mITT population, and clinical significance was assessed using the safety population. The key effectiveness outcomes for this study are presented below in **Tables 18, 21, 22, and 25**, and in **Figures 10 to 15**.

### Near Visual Acuity at 40 cm

The primary study endpoint of monocular photopic distance-corrected near visual acuity (DCNVA) at 40 cm was achieved, demonstrating the effectiveness of the TECNIS Synergy™ IOL in providing substantially improved near vision at 40 cm compared to an aspheric monofocal. The results of monocular (first eye) photopic (85 cd/m²) DCNVA testing at 40 cm at 6 months for both the Synergy™ and control groups are presented in **Table 17**. There was a statistically significant improvement (p<0.0001) in mean monocular distance corrected near visual acuity at 6 months in favor of the Synergy™ group (0.104 LogMAR), with an improvement of 4.2 lines, or 0.42 LogMAR over the control group.

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Summary of Safety and Effectiveness Data (SSED)  
 TECNIS Synergy™ IOLs, Models ZFR00V, DFR00V, ZFW150, ZFW225, ZFW300, ZFW375, DFW150, DFW225, DFW300 and DFW375

**Mean Near Visual Acuity at 40 cm at 6 Months**

|  Near (40 cm) Visual Acuity | Lens Group | Monocular |   |   |   |   | Binocular  |   |   |   |   |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
|   |   |  N | n | Mean LogMAR | Snellen Equiv. | Line Change vs. Control^{a} | N | n | Mean LogMAR | Snellen Equiv. | Line Change vs. Control^{a}  |
|  Uncorrected | TECNIS Synergy | Not tested | 131 | 131 | 0.060 | 20/23 | 3.3 lines  |   |   |   |   |
|   |  TECNIS monofocal |   |   |   |   |   | 131 | 130 | 0.393 | 20/49 |   |
|  Distance Corrected | TECNIS Synergy | 131 | 131 | 0.104 | 20/25 | 4.2 lines^{b} | 131 | 131 | 0.047 | 20/22 | 3.6 lines  |
|   |  TECNIS monofocal | 131 | 130 | 0.522 | 20/67 |  | 131 | 130 | 0.403 | 20/51 |   |
|  Mesopic Distance Corrected | TECNIS Synergy | 131 | 131 | 0.315 | 20/41 | 3.4 lines | 131 | 131 | 0.244 | 20/35 | 3.5 lines  |
|   |  TECNIS monofocal | 131 | 130 | 0.654 | 20/90 |  | 131 | 130 | 0.591 | 20/78 |   |

$^{a}$ Line difference (control minus Synergy) is converted directly from LogMAR difference.

$^{b}$ Synergy met the primary study endpoint of significantly better mean DCNVA than control (p<0.0001, one-sided two-sample t-test) and a mean DCNVA of 0.104 LogMAR (Safety population).

Monocular near (40 cm) visual acuity distributions for both lens groups are presented in **Tables 19A and 19B**; binocular near (40 cm) visual acuity distributions are presented in **Tables 20A and 20B**. Near (40 cm) visual acuity results demonstrate the effectiveness of the Synergy lens in providing improved near vision compared to the monofocal control lens.

**Distribution of Monocular Distance-Corrected Near Visual Acuity**

|  Monocular Snellen Visual Acuity | TECNIS Synergy N=131 |   | TECNIS monofocal N=131  |   |
| --- | --- | --- | --- | --- |
|   |  n | % | n | %  |
|  20/20^{2} or better | 44 | 33.6% | 2 | 1.5%  |
|  20/25^{2} or better | 92 | 70.2% | 7 | 5.4%  |
|  20/32^{2} or better | 119 | 90.8% | 10 | 7.7%  |
|  20/40^{2} or better | 124 | 94.7% | 25 | 19.2%  |
|  Worse than 20/40^{2} | 7 | 5.3% | 105 | 80.8%  |
|  **Total n** | **131** |  | **130** |   |

%=(n/Total n) * 100

Page 35 of 53

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Summary of Safety and Effectiveness Data (SSED)  
 TECNIS Synergy™ IOLs, Models ZFR00V, DFR00V, ZFW150, ZFW225, ZFW300, ZFW375, DFW150, DFW225, DFW300 and DFW375

**Distribution of Monocular Distance-Corrected Near Visual Acuity**

|  Monocular LogMAR Visual Acuity | TECNIS Synergy N=131 |   | TECNIS monofocal N=131  |   |
| --- | --- | --- | --- | --- |
|   |  n | % | n | %  |
|  0.00 LogMAR or better | 33 | 25.2% | 0 | 0.0%  |
|  0.10 LogMAR or better | 76 | 58.0% | 6 | 4.6%  |
|  0.20 LogMAR or better | 110 | 84.0% | 9 | 6.9%  |
|  0.30 LogMAR or better | 123 | 93.9% | 19 | 14.6%  |
|  Worse than 0.30 LogMAR | 8 | 6.1% | 111 | 85.4%  |
|  **Total n** | **131** |  | **130** |   |

%=(n/Total n) * 100

**Distribution of Binocular Uncorrected Near Visual Acuity**

|  Binocular Snellen Visual Acuity | TECNIS Synergy N=131 |   | TECNIS monofocal N=131  |   |
| --- | --- | --- | --- | --- |
|   |  n | % | n | %  |
|  20/20^{-2} or better | 61 | 46.6% | 0 | 0.0%  |
|  20/25^{-2} or better | 114 | 87.0% | 158 | 6.2%  |
|  20/32^{-2} or better | 122 | 93.1% | 25 | 19.2%  |
|  20/40^{-2} or better | 127 | 96.9% | 57 | 43.8%  |
|  Worse than 20/40^{-2} | 4 | 3.1% | 73 | 56.2%  |
|  **Total n** | **131** |  | **130** |   |

%=(n/Total n) * 100

Page 36 of 53

{36}

Summary of Safety and Effectiveness Data (SSED)  
 TECNIS Synergy™ IOLs, Models ZFR00V, DFR00V, ZFW150, ZFW225, ZFW300, ZFW375, DFW150, DFW225, DFW300 and DFW375

**Distribution of Binocular Uncorrected Near Visual Acuity**

|  Binocular LogMAR Visual Acuity | TECNIS Synergy N=131 |   | TECNIS monofocal N=131  |   |
| --- | --- | --- | --- | --- |
|   |  n | % | n | %  |
|  0.00 LogMAR or better | 43 | 32.8% | 0 | 0.0%  |
|  0.10 LogMAR or better | 101 | 77.1% | 2 | 1.5%  |
|  0.20 LogMAR or better | 120 | 91.6% | 14 | 10.8%  |
|  0.30 LogMAR or better | 126 | 96.2% | 42 | 32.3%  |
|  Worse than 0.30 LogMAR | 5 | 3.8% | 88 | 67.7%  |
|  **Total n** | **131** |  | **130** |   |

%=(n/Total n) * 100

### Near Visual Acuity at 33 cm

The secondary study endpoint of monocular DCNVA at 33 cm was achieved, demonstrating that the TECNIS Synergy™ IOL provides substantially improved near vision at 33 cm compared to an aspheric monofocal. The results of near visual acuity testing at 33 cm under photopic (85 cd/m²) lighting conditions at 6 months for both Synergy™ and control groups are presented in **Table 21**. There was a statistically significant improvement (p<0.0001) in mean monocular DCNVA at 33 cm at 6 months in favor of the Synergy™ group (mean 0.154 LogMAR), with an improvement of 4.5 lines, or 0.455 LogMAR over the control group.

**Mean Monocular Near Visual Acuity at 33 cm at 6 Months**

|  Lens Group | N | n | Mean LogMAR | Snellen Equivalent | Line Change vs. Control^{a}  |
| --- | --- | --- | --- | --- | --- |
|  TECNIS Synergy | 131 | 131 | 0.154 | 20/29 | 4.5 lines^{b}  |
|  TECNIS monofocal | 131 | 130 | 0.608 | 20/81  |   |

$^{a}$ Line difference (control minus Synergy) is converted directly from LogMAR difference.

$^{b}$ Synergy met the secondary study endpoint of significantly better mean DCNVA at 33 cm than control (p<0.0001, one-sided two-sample t-test) and a mean DCNVA of 0.154 LogMAR (Safety population).

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Summary of Safety and Effectiveness Data (SSED)  
 TECNIS Synergy™ IOLs, Models ZFR00V, DFR00V, ZFW150, ZFW225, ZFW300, ZFW375, DFW150, DFW225, DFW300 and DFW375

## Intermediate Visual Acuity

The secondary effectiveness study endpoint of monocular, photopic DCIVA at 66 cm was achieved, demonstrating that the TECNIS Synergy™ IOL provides substantially improved intermediate vision compared to an aspheric monofocal. The results of intermediate visual acuity testing at 66 cm under photopic (85 cd/m²) lighting conditions at 6 months for both Synergy™ and control IOL groups are presented in **Table 22**. There was a statistically significant improvement (p<0.0001) in mean monocular DCIVA at 6 months in favor of the Synergy™ lens (0.060 LogMAR), with an improvement of 2.8 lines, or 0.275 LogMAR over the control group.

**Mean Intermediate Visual Acuity at 66 cm at 6 Months**

|  Intermediate Visual Acuity | Lens Group | Monocular |   |   |   |   | Binocular  |   |   |   |   |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
|   |   |  N | n | Mean LogMAR | Snellen Equiv. | Line Change vs. Control^{a} | N | n | Mean LogMAR | Snellen Equiv. | Line Change vs. Control^{a}  |
|  Uncorrected | TECNIS Synergy | Not Tested | 131 | 131 | 0.022 | 20/21 | 1.8 lines  |   |   |   |   |
|   |  TECNIS monofocal |   |   |   |   |   | 131 | 130 | 0.199 | 20/32 |   |
|  Distance Corrected | TECNIS Synergy | 131 | 131 | 0.060 | 20/23 | 2.8 lines^{b} | Not Tested  |   |   |   |   |
|   |  TECNIS monofocal | 131 | 130 | 0.335 | 20/43 |   |   |   |   |   |   |

$^{a}$ Line difference (control minus Synergy) is converted directly from LogMAR difference.

$^{b}$ Synergy met the secondary study endpoint of significantly better mean DCIVA than control (p<0.0001, one-sided two-sample t-test) and a mean DCIVA of 0.060 LogMAR (Safety population).

Monocular intermediate visual acuity distributions for both lens groups are presented in **Tables 23A and 23B**; binocular intermediate visual acuity distributions are presented in **Tables 24A and 24B**. Overall, the intermediate visual acuity results demonstrate the effectiveness of the Synergy lens to provide improved intermediate vision compared to the monofocal control lens.

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Summary of Safety and Effectiveness Data (SSED)
TECNIS Synergy™ IOLs, Models ZFR00V, DFR00V, ZFW150, ZFW225, ZFW300, ZFW375, DFW150, DFW225, DFW300 and DFW375

Table 23A
Distribution of Monocular Distance-Corrected Intermediate
Visual Acuity at 66 cm at 6 Months

|  Monocular Snellen Visual Acuity | TECNIS Synergy N=131 |   | TECNIS monofocal N=131  |   |
| --- | --- | --- | --- | --- |
|   |  n | % | n | %  |
|  20/20^{-2} or better | 72 | 55.0% | 8 | 6.2%  |
|  20/25^{-2} or better | 105 | 80.2% | 17 | 13.1%  |
|  20/32^{-2} or better | 125 | 95.4% | 37 | 28.5%  |
|  20/40^{-2} or better | 129 | 98.5% | 68 | 52.3%  |
|  Worse than 20/40^{-2} | 2 | 1.5% | 62 | 47.7%  |
|  **Total n** | **131** |  | **130** |   |

Monocular UCIVA was not tested
%=(n/Total n) * 100

Table 23B
Distribution of Monocular Distance-Corrected Intermediate
Visual Acuity at 66 cm at 6 Months

|  Monocular LogMAR Visual Acuity | TECNIS Synergy N=131 |   | TECNIS monofocal N=131  |   |
| --- | --- | --- | --- | --- |
|   |  n | % | n | %  |
|  0.00 LogMAR or better | 47 | 35.9% | 4 | 3.1%  |
|  0.10 LogMAR or better | 97 | 74.0% | 10 | 7.7%  |
|  0.20 LogMAR or better | 117 | 89.3% | 24 | 18.5%  |
|  0.30 LogMAR or better | 127 | 96.9% | 55 | 42.3%  |
|  Worse than 0.30 LogMAR | 4 | 3.1% | 75 | 57.7%  |
|  **Total n** | **131** |  | **130** |   |

Monocular UCIVA was not tested
%=(n/Total n) * 100

Page 39 of 53

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Summary of Safety and Effectiveness Data (SSED)  
 TECNIS Synergy™ IOLs, Models ZFR00V, DFR00V, ZFW150, ZFW225, ZFW300, ZFW375, DFW150, DFW225, DFW300 and DFW375

**Distribution of Binocular Uncorrected Intermediate Visual Acuity**

|  Binocular Snellen Visual Acuity | TECNIS Synergy N=131 |   | TECNIS monofocal N=131  |   |
| --- | --- | --- | --- | --- |
|   |  n | % | n | %  |
|  20/20^{-2} or better | 84 | 64.1% | 18 | 13.8%  |
|  20/25^{-2} or better | 117 | 89.3% | 44 | 33.8%  |
|  20/32^{-2} or better | 130 | 99.2% | 96 | 73.8%  |
|  20/40^{-2} or better | 131 | 100.0% | 1…

---

**Source:** [https://fda.innolitics.com/device/P980040S124](https://fda.innolitics.com/device/P980040S124)

**Published by [Innolitics](https://innolitics.com)** — a medical-device software consultancy. We help companies design, build, and clear FDA-regulated software and AI/ML devices. If you're preparing [a PMA](https://innolitics.com/services/regulatory/), [a 510(k)](https://innolitics.com/services/510ks/), [a SaMD](https://innolitics.com/services/end-to-end-samd/), [an AI/ML medical device](https://innolitics.com/services/medical-imaging-ai-development/), or [an FDA regulatory strategy](https://innolitics.com/services/regulatory/), [get in touch](https://innolitics.com/contact).

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