TECNIS MULTIFOCAL 1-PIECE INTRAOCULAR LENS (IOL)
Device Facts
| Record ID | P980040S049 |
|---|---|
| Device Name | TECNIS MULTIFOCAL 1-PIECE INTRAOCULAR LENS (IOL) |
| Applicant | Johnson & Johnson Surgical Vision, Inc. |
| Product Code | MFK · Ophthalmic |
| Decision Date | Dec 17, 2014 |
| Decision | APPR |
| Regulation | 21 CFR 886.3600 |
| Device Class | Class 3 |
| Attributes | Therapeutic, Real-World Evidence |
Real-World Evidence
| Submission | Device | Sponsor | RWD Sources | RWE Use Summary | Key Tags |
|---|---|---|---|---|---|
| P980040S049 · Dec 17, 2014 | TECNIS MULTIFOCAL 1-PIECE INTRAOCULAR LENS (IOL) | Johnson & Johnson Surgical Vision, Inc. | European market assessment registry/clinical data | Supplemental clinical information from a European market assessment study was used to support the safety and effectiveness of the TECNIS Multifocal IOLs (Models ZKB00 and ZLB00) by providing real-world clinical outcomes, including visual acuity and adverse event rates, consistent with the primary IDE study. | Market assessment; European registry; Post-market clinical data |
Clinical Evidence
| Study Design | Population | Comparator | Key Endpoints |
|---|---|---|---|
| Market Assessment Study; Prospective, multi-center, bilateral, open-label market assessment; Follow-up/Duration: 3 months; Study Period: October 2013 (marketed as of) | 30 subjects (15 ZKB00, 15 ZLB00) in three EU countries; Sample Size: 30; Number of Sites: 6 | Not applicable for this study | Visual acuity (UCDVA, BCDVA, UCNVA, DCNVA), spectacle independence, and adverse events |
Indications for Use
The TECNIS® Multifocal 1-Piece intraocular lenses, Models ZKB00 and ZLB00, are indicated for primary implantation for the visual correction of aphakia in adult patients with and without presbyopia in whom 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.
Device Story
TECNIS® Multifocal 1-Piece IOLs (Models ZKB00, ZLB00) are posterior chamber IOLs for cataract patients; they utilize an aspheric anterior and diffractive multifocal posterior optic to provide near, intermediate, and distance vision. The device is implanted by a surgeon during phacoemulsification cataract surgery. The lens functions by splitting light to provide multiple focal points, reducing dependence on reading glasses. Patients may experience common multifocal IOL side effects like halos, glare, or reduced contrast sensitivity. The device benefits patients by providing spectacle independence for various distances. Clinical outcomes are assessed via visual acuity testing and patient questionnaires.
Clinical Evidence
Prospective, multicenter, bilateral, open-label, 3-armed clinical study (N=445) comparing ZKB00 and ZLB00 to a monofocal control (ZCB00). Primary endpoint: mean monocular DCNVA at 40 cm at 6 months. Results: ZKB00 and ZLB00 showed statistically significant improvement (p<0.0001) of 3.3 and 4.0 lines respectively over control. Secondary endpoints: defocus range (p<0.0001), spectacle independence, and combined visual acuity (p<0.0001) favored multifocal lenses. Safety profile: adverse event rates were low and comparable to ISO SPE rates; optical symptoms (halos) were expected for multifocal IOLs.
Technological Characteristics
Hydrophobic SENSAR® soft acrylic material with polyethylene glycol surface treatment; UV cutoff at 375-380nm. Aspheric anterior and diffractive multifocal posterior optic. 6.0mm optic diameter, 13.0mm overall length. TRI-FIX haptic design. Index of refraction 1.47 at 35°C. Sterilized via ethylene oxide.
Indications for Use
Indicated for primary implantation for visual correction of aphakia in adult patients (with/without presbyopia) post-phacoemulsification cataract removal, desiring near, intermediate, and distance vision with increased spectacle independence. Intended for capsular bag placement.
Regulatory Classification
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 1-Piece IOL, Model ZMB00 (P980040/S029)
- SENSAR 1-Piece lens, Model AAB00 (P980040/S015)
- Silicone TECNIS® Multifocal 3-Piece lens, Model ZM900 (P080010)
Reference Devices
- TECNIS® 1-Piece IOL Model ZCB00
Submission Summary (Full Text)
{0}
# SUMMARY OF SAFETY AND EFFECTIVENESS DATA (SSED)
## I. GENERAL INFORMATION
Device Generic Name: Lens, Multifocal Intraocular
Device Trade Name: TECNIS® Multifocal 1-Piece Intraocular Lens, Models ZKB00 and ZLB00
Device Procode: MFK
Applicant's Name and Address: Abbott Medical Optics Inc.
1700 East Saint Andrew Place
Santa Ana, CA 92705
Premarket Approval Application (PMA) Number: P980040/S049
Date(s) of Panel Recommendation: None
Date of FDA Notice of Approval: December 17, 2014
The TECNIS® Multifocal 1-Piece Intraocular Lenses (IOLs), Models ZKB00 (+2.75 D) and ZLB00 (+3.25 D) are extensions of AMO’s FDA-approved TECNIS® Multifocal 1-Piece IOL, Model ZMB00 (+4.00 D) (PMA P980040/S029), which was approved on January 22, 2010. The ZKB00 and ZLB00 IOLs share the same lens material and optic platform as the ZMB00 lenses, but with lower add powers of +2.75 D and +3.25 D, respectively. The TECNIS® Multifocal 1-Piece IOLs, Models ZKB00 and ZLB00 combine the features of the two FDA-approved parent lenses: the SENSAR 1-Piece lens, Model AAB00 (monofocal mechanical parent), approved on October 10, 2007 under P980040/S015, and the Silicone TECNIS® Multifocal 3-Piece lens, Model ZM900 (multifocal optical parent) approved on January 16, 2009 under P080010. Like the multifocal optical parent, the ZKB00 and ZLB00 lenses are designed with the same optical features available with the ZM900 parent lens; which include an aspheric optic, diffractive multifocal posterior optic profile, and the dioptic power range of +5.0 D to +34.0 D in 0.5 D increments. Models ZM900 and ZMB00 are indicated for primary implantation for the visual correction of aphakia in adult patients with and without presbyopia in whom a cataractous lens has been removed by phacoemulsification and who desire near, intermediate and distance vision with increased spectacular independence. Model AAB00 is indicated for visual correction of aphakia in adult patients whom a cataractous lens have been removed by extracapsular extraction. The SSED to support these indications are available on the CDRH website and is incorporated by reference here. The current supplement was submitted to include Models ZKB00 and ZLB00 for the TECNIS® Multifocal 1- Piece IOL.
PMA P980040/S049: FDA Summary of Safety and Effectiveness Data
Page 1
{1}
## II. INDICATIONS FOR USE
The TECNIS® Multifocal 1-Piece intraocular lenses, Models ZKB00 and ZLB00, are indicated for primary implantation for the visual correction of aphakia in adult patients with and without presbyopia in whom 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.
### III. CONTRAINDICATIONS
None.
### IV. WARNINGS AND PRECAUTIONS
The warnings and precautions can be found in the TECNIS® Multifocal 1-Piece IOL labeling.
### V. DEVICE DESCRIPTION
The TECNIS® Multifocal 1-Piece Intraocular Lenses (IOLs), Models ZKB00 and ZLB00, are ultraviolet light-absorbing posterior chamber IOLs on a one-piece multifocal platform. The lenses are available in two add powers: Model ZKB00 has an add power of +2.75 D and Model ZLB00 has an add power of +3.25 D. All models of the TECNIS® Multifocal 1-Piece IOLs are available in the dioptric power range of +5.0 D to +34.0 D in 0.5 D increments.
A summary of the physical characteristics of the TECNIS® Multifocal 1-Piece IOLs is provided in Table 1.
Table 1:
Summary of Physical Characteristics
| TECNIS® Multifocal 1-Piece IOL | | |
| --- | --- | --- |
| Model Numbers | ZKB00 | ZLB00 |
| Optic Type | Aspheric Anterior and Diffractive (Multifocal) Posterior Optic | |
| Optic/Haptic Material | FDA-approved hydrophobic SENSAR® soft acrylic material with polyethylene glycol surface treatment UV cutoff at 10% Transmittance: | |
| *Measured in Water | 375nm* (5.0 diopter lens) 380nm* (34.0 diopter lens) | |
| IOL Power (Diopter) | +5.0 D to +34.0 D in +0.5 D increments | |
| Add Power at IOL Plane (Diopter) | +2.75 D | +3.25 D |
| Index of Refraction | 1.47 at 35°C | |
| Haptic Configuration | TRI-FIX design Modified C, integral with optic | |
| Optic Diameter | 6.0mm | |
| Overall Length | 13.0mm | |
| Haptic Angle | 0° | |
PMA P980040/S049: FDA Summary of Safety and Effectiveness Data
Page 2
{2}
## **VI. ALTERNATIVE PRACTICES AND PROCEDURES**
There are several other alternatives for providing this optical correction that is needed after cataract extraction, such as eye glasses, contact lenses, or intraocular lenses (IOLs) of different types. 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® Multifocal 1-Piece IOLs, Models ZKB00 and ZLB00, are currently available in Australia, European Union, Hong Kong, India, Israel, New Zealand, Norway, Saudi Arabia, Serbia and Montenegro, Singapore, South Africa, Switzerland, Turkey, and Korea. The lenses have not been withdrawn from any country for any reason related to safety or effectiveness.
## **VIII. POTENTIAL ADVERSE EFFECTS OF THE DEVICE ON HEALTH**
Potential adverse events and complications accompanying cataract or implant surgery may include, but are not limited to the following: corneal endothelial damage, infection (endophthalmitis), retinal detachment, vitritis, cystoid macular edema, corneal edema, pupillary block, iris prolapse, hypopyon, elevated Intraocular Pressure (IOP) requiring treatment, and secondary surgical intervention.
Secondary surgical interventions include, but are not limited to, lens repositioning (due to decentration, subluxation, etc.), vitreous aspirations or iridectomy for pupillary block, wound leak repair, retinal detachment repair, corneal transplant, lens replacement due to refractive error, and unacceptable optical/visual symptoms or severe inflammation. Multifocal IOLs in some patients can cause perception of halos around lights, glare, and other visual disturbances including reduced contrast sensitivity.
For the specific adverse events that occurred during the TECNIS® Multifocal 1-Piece IOL clinical study, please see the *Summary of Primary Clinical Study*, Section X.
## **IX. SUMMARY OF PRECLINICAL STUDIES**
The preclinical studies performed support the safety and effectiveness of the TECNIS® Multifocal 1-Piece IOLs. The results of these studies are summarized below.
PMA P980040/S049: FDA Summary of Safety and Effectiveness Data
Page 3
{3}
# A. Laboratory Studies
# 1. Physicochemical and Biocompatibility Testing
All physicochemical and biocompatibility testing are incorporated by reference to P980040/S015 and P980040/S029. No additional testing was needed to support the current submission.
# 2. Dimensional, Optical, and Mechanical Testing
Prior to design verification testing, a risk assessment was conducted to determine the appropriate dimensional, optical, mechanical and cosmetic tests required to mitigate any new risks identified for the TECNIS® Multifocal 1-Piece IOLs, Models ZKB00 and ZLB00. The ZKB00 and ZLB00 lenses have identical mechanical and similar optical properties as the sibling lens, the TECNIS® Multifocal 1-Piece, Model ZMB00 (P980040/S029). Therefore, the dimensional and mechanical testing conducted in accordance with the requirements of ISO 11979-3:2006, Part 3: Mechanical properties and test methods, 11979-9:2006 for this lens model are incorporated by reference to P980040/S029 and P980040/S015.
Required dimensional, optical, and mechanical testing was performed on finished, sterilized TECNIS® Multifocal 1-Piece IOLs, Models ZKB00 and ZLB00 to verify the design's conformance to the American National Standards Institute (ANSI) Standard for Multifocal IOLs, ANSI Z80.12: 2007, ANSI Standard for Ophthalmics – Multifocal Intraocular Lenses as well ISO 11979-2:1999 Part 2: Optical properties and test methods, ISO 11979-3:2006, Part 3: Mechanical properties and test methods, 11979-9:2006, Part 9: Multifocal Intraocular Lenses, and internal specifications. Folding and insertion testing was also performed to verify recovery of lens properties, such as dioptric power, cosmetic and image quality, following simulated insertion. The ZKB00 and ZLB00 lenses passed all required tests established in the ANSI Z80.12 and ISO 11979-2:1999, 11979-3:2006, and 11979-9:2006 and met product specifications. A summary of the results of the dimensional, optical and mechanical testing performed are summarized in Table 2.
PMA P980040/S049: FDA Summary of Safety and Effectiveness Data
Page 4
{4}
**Table 2:**
**Dimensional, Optical and Mechanical Test Requirements Summary**
| Test | Purpose | Acceptance Criteria | Results |
| --- | --- | --- | --- |
| **Optical Requirements** | | | |
| Dioptric Power | To determine the base dioptric power of the lenses | Dioptric Power P ≤ 15.0 D ±0.3D tolerance 15.0 D < P ≤ 25.0 D ±0.4D tolerance 25.0 D < P ≤ 30.0 D ±0.5D tolerance >30.0 D ±1.0D tolerance | Pass |
| Image Quality | To evaluate the quality of the image produced by the lenses | ISO eye model Per ISO 11979-9: Mean MTF value minus two standard deviations | Pass |
| **Recovery of Properties Following Simulated Surgical Manipulation** | | | |
| Dioptric Power | To determine the base dioptric power of the lenses | Dioptric Power P ≤ 15.0 D ±0.3D tolerance 15.0 D < P ≤ 25.0 D ±0.4D tolerance 25.0 D < P ≤ 30.0 D ±0.5D tolerance >30.0 D ±1.0D tolerance | Pass |
| Image Quality | To evaluate the quality of the image produced by the lenses | ISO eye model Per ISO 11979-9: Mean MTF value minus two standard deviations | Pass |
| Surface and Bulk Homogeneity | To determine if the lenses are essentially free from defects | Essentially free from defects and deviations from intended features of design | Pass |
2. Sterilization, Packaging, Shelf Life and Transport Stability Testing
The TECNIS® Multifocal 1-Piece IOLs (Models ZKB00 and ZLB00) are packaged in a polypropylene lens insert that is placed into a polycarbonate “daisy wheel” lens case, and sealed in double Tyvek/Mylar pouches. Pouched lenses are sterilized using ethylene oxide (EO). The EO process was validated using the “overkill” method to demonstrate that the process achieves a sterility assurance level (SAL) of 10⁻⁶. In addition, the shelf life and transport stability studies demonstrate that the packaging configuration maintains its sterile barrier and protects the lens during transport. Testing was conducted in accordance with the following Standards and United States Pharmacopoeial 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 34/ Chapter 29 2011, *Bacterial Endotoxin Testing*
PMA P980040/S049: FDA Summary of Safety and Effectiveness Data
Page 5
{5}
- ISO 11979-6, *Ophthalmic Implants – Intraocular Lenses – Part 6: Shelf-life and transport stability*
The results of the sterilization, packaging, shelf life and transport stability studies are summarized in Table 3.
**Sterilization, Packaging, Shelf Life and Transport Stability Test Results**
| Test | Purpose | Acceptance Criteria | Results |
| --- | --- | --- | --- |
| EO Validation | Evaluate sterility | No positive biological indicators | Pass |
| Ethylene Oxide Residuals | Evaluate toxicity | ≤1.25 µg/IOL | Pass |
| Ethylene Chlorohydrin Residuals | Evaluate toxicity | ≤5.0 µg/IOL | Pass |
| Bioburden | Evaluate sterility | <100 cfu/IOL | Pass |
| Bacterial endotoxin | Evaluate sterility | <0.1 EU/IOL | Pass |
| Package Evaluation – Outer Pouch Burst strength | Evaluate seal integrity | Burst strength ≥ 24” in water | Pass |
| Package Evaluation – Inner Pouch Burst strength | Evaluate Package Seal Integrity | Burst strength ≥ 28” in water | Pass |
| Package Evaluation – Microbial Barrier Testing (Aerosol Challenge Test) | Evaluate Whole Package Integrity | No growth of challenge organism | Pass |
| Transport Stability | Evaluate package integrity and device stability | Manufacturing specification met after exposing samples to simulated transport conditions. | Pass |
| Exhaustive Extraction | To evaluate potential for toxic extractable components during shelf life | Conforms to SENSAR acrylic historical norms | Conforms |
PMA P980040/S049: FDA Summary of Safety and Effectiveness Data
Page 6
{6}
## **X. SUMMARY OF PRIMARY CLINICAL STUDIES**
The applicant performed a clinical study to establish a reasonable assurance of safety and effectiveness of cataract surgery and intraocular lens implantation with the TECNIS® Multifocal 1-Piece IOLs, Models ZKB00 and ZLB00 for primary implantation for the visual correction of aphakia in adult patients. The TECNIS® Multifocal IOLs, Models ZKB00 and ZLB00, are made of the same materials and geometry as the currently marketed TECNIS® Multifocal IOL, Model ZMB00; however, with lower IOL add powers (ZKB00 +2.75 D, ZLB00 +3.25 D, and ZMB00 +4.00 D). The study was conducted in the U.S. and the U.K. under G120091. Data from this clinical study were the basis for the PMA approval decision. A summary of the clinical study is presented below.
### **A. Study Design**
The study began on 11/6/2012 and all 6-month visits were complete as of 10/21/2013. The database for this PMA supplement was locked for analysis on 10/28/2013 and included 445 implanted subjects. (The study was a 1-year study and the applicant provided an update on safety in Amendment 1.) There were 19 investigative sites.
The study was a prospective, multicenter, bilateral, open-label, evaluator-masked, modified-parallel group, 3-armed, 1-year clinical investigation designed to evaluate approximately 150 bilateral ZKB00 subjects, 150 bilateral ZLB00 subjects and 150 bilateral TECNIS® monofocal ZCB00 control subjects (a legally marketed alternative with similar indications for use). Subjects, in consultation with their surgeon/investigators, chose the IOL model to be implanted.
Statistical analysis was based on frequentist and descriptive methods. The two TECNIS® Multifocal IOL models (ZKB00 and ZLB00) were compared to the monofocal control IOL (TECNIS® 1-Piece IOL Model ZCB00) for effectiveness endpoints and for the safety non-inferiority analysis of best corrected distance visual acuity (BCDVA) results. The primary analysis group consists of first-eye or binocular data as appropriate; second-eye data were considered supplementary. For monocular distance corrected near visual acuity (DCNVA) and binocular diopters of defocus (20/40 or better), mean values for each multifocal test lens group and the control lens group were compared using two-sample t-tests for superiority. For combined binocular distance and near visual acuity as well as spectacle independence, comparisons between lens groups were evaluated using logistic regression for imputed data or Fisher's Exact test for available binocular questionnaire data.
Missing data were imputed using multiple imputation methods. Because the treatment assignment was not randomized, propensity analysis was performed. For monocular DCNVA and binocular diopters of defocus (20/40 or better), mean values for each multifocal test lens group and the control lens group were compared using two-sample t-tests. The Type-I error rate was set at 2.5% (one-sided). Hierarchical methods were used to adjust for multiple comparisons related to the primary effectiveness endpoint with the hypothesis for the higher-add ZLB00 IOL (+3.25 D)
PMA P980040/S049: FDA Summary of Safety and Effectiveness Data
Page 7
{7}
tested first, followed by the lower-add ZKB00 IOL (+2.75 D). For combined binocular distance and near visual acuity as well as spectacle independence, comparisons between lens groups were evaluated using logistic regression for imputed data or Fisher's Exact test for available binocular questionnaire data. Complications and adverse events as well as the proportion of first eyes achieving 20/40 or better BCDVA were compared to ISO safety and performance endpoints (SPE) rates (ISO 11979-7:2006) for each multifocal test lens group using an Exact test based on the binomial distribution. Mean first-eye BCDVA for each multifocal test lens group were compared to the control lens group and analyzed using non-inferiority methods. Median binocular contrast sensitivity for each multifocal test lens group was compared to the control lens group.
Sample size was justified based on monocular, distance-corrected near visual acuity. There was over 90% power to detect a 0.7-line or greater difference in mean visual acuity between the test and control lens groups (assumes one-sided testing with an alpha of 0.025 and standard deviation of 1.6 lines) with 135 subjects in each lens group.
1. Clinical Inclusion and Exclusion Criteria
All subjects were enrolled from the normal cataract surgical populations at the investigative sites. In general, subjects were to have healthy eyes with no pathology other than cataract in both eyes.
Enrollment in the study was limited to patients who met the following key inclusion criteria:
- Age 18 or greater
- Bilateral cataracts for which phacoemulsification extraction and posterior IOL implantation have been planned for both eyes
- Preoperative best-corrected distance visual acuity (BCDVA) of 20/40 or worse, with or without a glare source
- Visual potential of 20/25 or better in each eye
- Preoperative corneal astigmatism of 1.0 D or less
Patients were not permitted to enroll in the study if they met any of the following exclusion criteria:
- Requiring an intraocular lens power outside the available range of +16.0 to +28.0 D
- Use of systemic or ocular medications that may affect vision or likely to impact pupil dilation or iris structure
- Acute or chronic disease or illness that would increase the operative risk or confound study outcome(s) (e.g., poorly controlled diabetes)
- Uncontrolled systemic or ocular disease
- History of ocular trauma, prior refractive or other ocular surgery or subjects expected to require retinal laser treatment or other surgical intervention
PMA P980040/S049: FDA Summary of Safety and Effectiveness Data
Page 8
{8}
- Presence of ocular pathology other than cataract such as:
- Amblyopia or strabismus or any inability to focus, fixate or maintain binocular vision
- Corneal abnormalities (including irregular astigmatism)
- Pupil abnormalities
- Capsule or zonule abnormalities
- Glaucomatous changes
- Intraocular inflammation
- Known pathology that may affect visual acuity and/or are predicted to cause future acuity losses to a level of 20/30 or worse (e.g., macular degeneration)
- Inability to achieve keratometric stability for contact lens wearers
- Desire for monovision correction
2. Follow-up Schedule
All patients in the study had regular examinations according to the schedule shown below, in Table 4.
Table 4:
Clinical Study Visit Schedule
| Visit | Exam | Eyes Evaluated | Visit Window |
| --- | --- | --- | --- |
| 1 | Preoperative Exam | Both Eyes | Within 30 days prior to 1^{st} surgery |
| 2 | Operative | 1^{st} Eye | 0-30 days following preoperative exam |
| 3 | Postop 1 (1 day) | 1^{st} Eye | 1-2 days postoperative |
| 4 | Postop 2 (1 week)* | 1^{st} Eye | 7-14 days postoperative |
| 5 | Operative | 2^{nd} Eye | Within 1 month after 1^{st} eye surgery |
| 6 | Postop 1 (1 day) | 2^{nd} Eye | 1-2 days postoperative |
| 7 | Postop 2 (1 week) | 2^{nd} Eye | 7-14 days postoperative |
| 8 | Postop 3 (1 month) | Both Eyes | 30-60 days postop from 2^{nd} eye surgery |
| 9 | Postop 4 (6 months) | Both Eyes | 120-180 days postop from 2^{nd} eye surgery |
| 10 | Postop 5 (1 year) | Both Eyes | 330-420 days postop from 2^{nd} eye surgery |
* Postop 2 for the first eye was to be completed prior to surgery on the second eye.
Preoperatively, the evaluations that were performed in relation to the index procedure, and postoperatively, the objective and subjective parameters measured during the study, are portrayed in Table 5. Adverse events and complications were recorded at all visits.
The key timepoint for evaluation of the safety and effectiveness outcomes was at 6 months postoperatively.
PMA P980040/S049: FDA Summary of Safety and Effectiveness Data
Page 9
{9}
Table 5: Summary of Examinations Required at Each Visit
| Examination | Preop Both eyes | Op 1 1^{st} eye | 1 day 1^{st} eye | 1 wk 1^{st} eye | Op 2 2^{nd} eye | 1 day 2^{nd} eye | 1 wk 2^{nd} eye | 1 mo Both eyes | 6 mos Both eyes | 1 year Both eyes |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
| Ocular history, inclusion/exclusion criteria | X | | | | | | | | | |
| Informed consent | X | | | | | | | | | |
| Potential visual acuity | X | | | | | | | | | |
| Targeted refraction/IOL power calculation/axial length | X | | | | | | | | | |
| Lens power/serial number/operative procedures | | X | | | X | | | | | |
| Manifest refraction (Snellen preop; ETDRS postop) | X | | | X | | | X | X | X | X |
| UCDVA-photopic, monocular (Snellen preop; ETDRS postop) | X | | | X | | | X | X | X | X |
| UCDVA-photopic, binocular (ETDRS) | | | | | | | | | X | X |
| BCDVA-photopic, monocular (Snellen preop; ETDRS postop) | X | | | X | | | X | X | X | X |
| BCDVA-photopic, binocular (ETDRS) | | | | | | | | | X | X |
| Binocular BCDVA defocus curve testing^{a} | | | | | | | | | X | |
| UCNVA-photopic, monocular at 40 cm and best distance (ETDRS) | | | | | | | | X | X | X |
| UCNVA-photopic, binocular at 40 cm and best distance (ETDRS) | | | | | | | | | X | X |
| DCNVA-photopic, monocular at 40 cm and best distance (ETDRS) | | | | | | | | X | X | X |
| DCNVA-photopic, binocular at 40 cm and best distance (ETDRS) | | | | | | | | | X | X |
| DCNVA-mesopic, monocular at 40 cm and best distance (ETDRS) | | | | | | | | | X | |
| DCNVA-mesopic, binocular at 40 cm and best distance (ETDRS) | | | | | | | | | X | |
| BCNVA-photopic, threshold with **minimum** add binocular at 40 cm | | | | | | | | | X | |
| Binocular best-corrected distance contrast sensitivity testing^{b} | | | | | | | | | X | |
| Pupil size, photopic | X | | | | | | | X | X | X |
| Pupil size, mesopic | | | | | | | | | X | |
| Keratometry | X^{c} | | | | | | | X | X | X |
| Intraocular pressure | X | | X | X | | X | X | X | X | X |
| Biomicroscopic slit-lamp exam^{d} | X | | X | X | | X | X | X | X | X |
| Dilated fundus exam | X | | | | | | | | X^{e} | X^{e,f} |
| Adverse events | | X | X | X | X | X | X | X | X | X |
| Ocular medications | X | X | X | X | X | X | X | X | X | X |
| Ocular symptoms | X | | X | X | | X | X | X | X | X |
| Subject questionnaire (by third party) | | | | | | | | | X | X |
$^{a}$Conducted on a subset of subjects
$^{b}$Under mesopic conditions with and without glare, and photopic conditions with glare
$^{c}$With corneal stability check for contact lens wearers
$^{d}$Includes determination of medical and lens findings/complications, including lens decentration and tilt
$^{e}$With fundus visualization
$^{f}$If medically indicated
PMA P980040/S049: FDA Summary of Safety and Effectiveness Data
Page 10
{10}
### 3. Clinical Endpoints
All clinical endpoints were evaluated at 6 months postoperatively. Because the lenses under study were modifications of approved IOLs, conclusions regarding device safety come primarily from the results from the study of the parent IOLs. See the SSED for the parent lenses for key safety results.
The key safety endpoints for this study were postoperative complication and adverse event rates vs. ISO SPE rates (ISO 11979-7:2006), binocular best corrected distance contrast sensitivity (mesopic with and without glare, and photopic with glare), mean monocular BCDVA compared to the monofocal control IOL, optical/visual symptoms, fundus visualization and lens stability.
The primary effectiveness endpoint was mean (LogMAR) DCNVA under photopic conditions at 40 cm. Secondary effectiveness endpoints were mean binocular best-corrected defocus range with 20/40 or better visual acuity (sub-study of ~60 subjects per arm), the proportion of subjects reporting that they 'never' wear glasses, and the proportion of subjects achieving combined BCDVA of 20/25 or better and binocular DCNVA of 20/32 or better.
Other endpoints included the proportion of eyes achieving monocular BCDVA of 20/40 or better vs. ISO SPE rates, binocular BCDVA, monocular and binocular uncorrected distance visual acuity (UCDVA), monocular and binocular uncorrected near visual acuity (UCNVA) at 40 cm and best distance, monocular DCNVA at best distance, binocular DCNVA at 40 cm and best distance, monocular and binocular mesopic DCNVA at 40 cm and best distance, binocular threshold best-corrected near visual acuity (BCNVA) with minimum add at 40 cm, and subject satisfaction/other questionnaire items.
The primary and secondary study endpoints were analyzed for three population groups: safety (all implanted eyes), intent-to-treat (ITT) with data imputation for missing values (included all implanted eyes and all subjects not necessarily implanted), and per-protocol (subjects/eyes without any protocol deviations). Safety endpoints were primarily analyzed using only the safety population. Although the primary analysis population group for the primary and secondary study endpoints was the ITT population, results presented in this summary are predominantly presented for the safety population for consistency.
### B. Accountability of PMA Cohort
A total of 445 subjects were enrolled and implanted in the clinical study across 19 clinical sites (18 in the US and 1 in the UK). Of these, 147 were in the ZKB00 IOL group, 150 in the ZLB00 IOL group and 148 in the monofocal control group. Only three subjects were not implanted bilaterally (2 ZKB00 and 1 ZCB00) for reasons unrelated to outcomes of the first-eye. At the time of database lock, of 445 subjects enrolled in the PMA study, 99% (441) primary eyes were available for analysis at time of endpoint evaluation, the 6-month postoperative visit.
PMA P980040/S049: FDA Summary of Safety and Effectiveness Data
Page 11
{11}
Subject accountability through 6 months is presented in Table 6 to Table 9 for ZKB00, ZLB00 and ZCB00 first-eyes (subjects), respectively. At 6 months, the overall percent accountability was 99.1% (441/445). Only four subjects (0.9%; 4/445) were unavailable at 6 months; 3 of which (0.7%; 3/445) were lost-to-follow-up due to reasons unrelated to vision, well below the general guideline of 10%.
**ZKB00 First Eye Accountability Through 6 Months**
| Subject status | 1 Day | | 1 Week | | 1 Month | | 6 Months | |
| --- | --- | --- | --- | --- | --- | --- | --- | --- |
| | n | % | n | % | n | % | n | % |
| **Total Available for Analysis** | **147** | **100** | **147** | **100** | **146** | **99.3** | **145** | **98.6** |
| --Out of Interval | 0 | 0.0 | 3 | 2.0 | 1 | 0.7 | 0 | 0.0 |
| --In Interval | 147 | 100 | 144 | 98.0 | 145 | 98.6 | 145 | 98.6 |
| Missing Subjects | 0 | 0.0 | 0 | 0.0 | 1 | 0.7 | 2 | 1.4 |
| --In interval or past interval (form not yet received) | 0 | 0.0 | 0 | 0.0 | 0 | 0.0 | 0 | 0.0 |
| --Active (not yet in visit interval) | 0 | 0.0 | 0 | 0.0 | 0 | 0.0 | 0 | 0.0 |
| --Missed visit | 0 | 0.0 | 0 | 0.0 | 1^{a} | 0.7 | 1^{b} | 0.7 |
| --Lost-to-follow-up | 0 | 0.0 | 0 | 0.0 | 0 | 0.0 | 1^{c,d} | 0.7 |
| --Discontinued | 0 | 0.0 | 0 | 0.0 | 0 | 0.0 | 0 | 0.0 |
$^{a}$ Subject 1023 missed visit but was seen at 6 months.
$^{b}$ Subject 813 missed visit due to illness.
$^{c}$ Subject 501 exited the study due to illness.
$^{d}$ Note: an additional subject (#1115) exited the study after the 6-month exam (moved out of state).
**ZLB00 First Eye Accountability Through 6 Months**
| Subject status | 1 Day | | 1 Week | | 1 Month | | 6 Months | |
| --- | --- | --- | --- | --- | --- | --- | --- | --- |
| | n | % | n | % | n | % | n | % |
| **Total Available for Analysis** | **150** | **100** | **150** | **100** | **149** | **99.3** | **150** | **100** |
| --Out of Interval | 0 | 0.0 | 1 | 0.7 | 1 | 0.7 | 2 | 1.3 |
| --In Interval | 150 | 100 | 149 | 99.3 | 148 | 98.7 | 148 | 98.7 |
| Missing Subjects | 0 | 0.0 | 0 | 0.0 | 1 | 0.7 | 0 | 0.0 |
| --In interval or past interval (form not yet received) | 0 | 0.0 | 0 | 0.0 | 0 | 0.0 | 0 | 0.0 |
| --Active (not yet in visit interval) | 0 | 0.0 | 0 | 0.0 | 0 | 0.0 | 0 | 0.0 |
| --Missed visit | 0 | 0.0 | 0 | 0.0 | 1^{a} | 0.7 | 0 | 0.0 |
| --Lost-to-follow-up | 0 | 0.0 | 0 | 0.0 | 0 | 0.0 | 0 | 0.0 |
| --Discontinued | 0 | 0.0 | 0 | 0.0 | 0 | 0.0 | 0 | 0.0 |
$^{a}$ Subject 1017 missed visit but was seen at 6 months.
PMA P980040/S049: FDA Summary of Safety and Effectiveness Data
Page 12
{12}
**Table 8:**
**ZCB00 First Eye Accountability Through 6 Months**
**Safety Population (N =148)**
| Subject status | 1 Day | | 1 Week | | 1 Month | | 6 Months | |
| --- | --- | --- | --- | --- | --- | --- | --- | --- |
| | n | % | n | % | n | % | n | % |
| **Total Available for Analysis** | **148** | **100** | **148** | **100** | **146** | **98.6** | **146** | **98.6** |
| --Out of Interval | 0 | 0.0 | 1 | 0.7 | 2 | 1.4 | 0 | 0.0 |
| --In Interval | 148 | 100 | 147 | 99.3 | 144 | 97.3 | 146 | 98.6 |
| Missing Subjects | 0 | 0.0 | 0 | 0.0 | 2 | 1.4 | 2 | 1.4 |
| --In interval or past interval (form not yet received) | 0 | 0.0 | 0 | 0.0 | 0 | 0.0 | 0 | 0.0 |
| --Active (not yet in visit interval) | 0 | 0.0 | 0 | 0.0 | 0 | 0.0 | 0 | 0.0 |
| --Missed visit | 0 | 0.0 | 0 | 0.0 | 0 | 0.0 | 0 | 0.0 |
| --Lost-to-follow-up | 0 | 0.0 | 0 | 0.0 | 2^{a,b} | 1.4 | 2^{a,b} | 1.4 |
| --Discontinued | 0 | 0.0 | 0 | 0.0 | 0 | 0.0 | 0 | 0.0 |
$^{a}$ Subject 1902 was uncooperative and refused further participation in the study.
$^{b}$ Subject 542 (unilateral subject) was uncooperative and refused further participation in the study prior to second-eye implantation.
Table 9 presents the questionnaire accountability at 6 months.
**Table 9:**
**Questionnaire Accountability at 6 Months**
**Bilateral Subjects - ZKB00, ZLB00 and ZCB00 Control**
**Safety Population**
| Subject status | ZKB00 | ZLB00 | ZCB00 |
| --- | --- | --- | --- |
| | N | n | n |
| Available for Analysis | 145 | 150 | 146 |
| Unilateral Subjects (not analyzed) | 2 | 0 | 0 |
| Did Not Complete Questionnaire | 1^{a} | 1^{a} | 1^{b} |
| **TOTAL** | **142** | **149** | **145** |
$^{a}$ Subjects were uncooperative when called for the questionnaire.
$^{b}$ Subject suffered a stroke following the 6-month visit and could not complete the questionnaire.
### **C. Study Population Demographics and Baseline Parameters**
The demographics of the study population were typical for an IOL study performed largely in the US. Subject demographics and preoperative baseline parameters were similar between the ZKB00 and ZLB00 lens groups vs. the ZCB00 control group. As this study was not randomized, age matching was performed during subject enrollment; analyses showed that mean ages between IOL groups were comparable with mean ages of approximately 68 in each lens group. Table 10 presents the demographic data for the ZKB00 and ZLB00 IOL groups vs. the ZCB00 control group. Table 11 and Table 12 present the key ocular baseline parameters.
PMA P980040/S049: FDA Summary of Safety and Effectiveness Data
Page 13
{13}
**Demographics for ZKB00, ZLB00 and ZCB00 Control Subjects**
| | | ZKB00 N=147 | ZLB00 N=150 | ZCB00 N=148 |
| --- | --- | --- | --- | --- |
| Age (years) | Mean | 67.6 | 67.9 | 68.5 |
| | Std | 6.9 | 6.8 | 6.8 |
| | Median | 69 | 67 | 69 |
| | Min | 48 | 49 | 49 |
| | Max | 84 | 85 | 86 |
| | Not Reported | 0 | 0 | 0 |
| | P-Value vs. ZCB00 | 0.2520^{a} | 0.4821^{a} | N/A |
| Age Group | <60 | 21 (14.3%) | 18 (12.0%) | 13 (8.8%) |
| | 60-69 | 58 (39.5%) | 68 (45.3%) | 67 (45.3%) |
| | 70-79 | 66 (44.9%) | 59 (39.3%) | 60 (40.5%) |
| | ≥80 | 2 (1.4%) | 5 (3.3%) | 8 (5.4%) |
| | Not Reported | 0 - | 0 - | 0 - |
| Sex | Male | 73 (49.7%) | 49 (32.7%) | 63 (42.6%) |
| | Female | 74 (50.3%) | 101 (67.3%) | 85 (57.4%) |
| | Not Reported | 0 - | 0 - | 0 - |
| | P-Value vs. ZCB00 | 0.2437^{b} | 0.0940^{b} | N/A |
| Race | Asian | 5 (3.4%) | 4 (2.7%) | 2 (1.4%) |
| | African American | 5 (3.4%) | 6 (4.0%) | 4 (2.7%) |
| | Caucasian | 137 (93.2%) | 140 (93.3%) | 142 (95.9%) |
| | Not Reported | 0 - | 0 (0.0%) | 0 - |
| | P-Value vs. ZCB00 | 0.4196^{b} | 0.6725^{b} | N/A |
| Iris Color | Blue/Gray | 59 (40.1%) | 49 (32.7%) | 58 (39.2%) |
| | Brown/Black | 50 (34.0%) | 68 (45.3%) | 55 (37.2%) |
| | Green/Hazel | 38 (25.9%) | 33 (22.0%) | 35 (23.6%) |
| | Not Reported | 0 - | 0 - | 0 - |
| | P-value vs. ZCB00 | 0.8419^{b} | 0.3340^{b} | N/A |
%=n/N(Total) excluding not reported
$^{a}$ P value from 2-sided 2-sample t-test
$^{b}$ P value from 2-sided Fisher's exact test
PMA P980040/S049: FDA Summary of Safety and Effectiveness Data
Page 14
{14}
**Table 11:**
**Mean Target Spherical Equivalent, Preop Keratometric Cylinder and IOL Power Implanted**
**First Eyes - ZKB00 and ZCB00 Control**
**Safety Population**
| Variable | IOL | N | Mean | Std. Dev. | Median | Min. | Max. | Lower 95% Conf. Limit | Upper 95% Conf. Limit | P Value^{a} |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
| Target Spherical Equivalent (D) | ZKB00 | 147 | -0.050 | 0.106 | -0.060 | -0.28 | 0.22 | -0.065 | -0.036 | - |
| ZCB00 | 148 | -0.070 | 0.126 | -0.080 | -0.49 | 0.40 | -0.088 | -0.053 | - |
| Difference | - | 0.020 | - | - | - | - | -0.002 | 0.042 | 0.1399 |
| Keratometric Cylinder (D) | ZKB00 | 147 | 0.510 | 0.243 | 0.500 | 0.00 | 1.00 | 0.477 | 0.543 | - |
| ZCB00 | 148 | 0.543 | 0.266 | 0.570 | 0.00 | 1.09 | 0.507 | 0.579 | - |
| Difference | - | -0.033 | - | - | - | - | -0.082 | 0.016 | 0.2652 |
| IOL Power Implanted (D) | ZKB00 | 147 | 21.136 | 2.511 | 21.000 | 16.00 | 27.00 | 20.793 | 21.479 | - |
| ZCB00 | 148 | 21.044 | 1.992 | 21.000 | 16.00 | 28.00 | 20.773 | 21.315 | - |
| Difference | - | 0.092 | - | - | - | - | -0.344 | 0.528 | 0.7274 |
$^{a}$ P-Value from 2-sided 2-sample t-test
**Table 12:**
**Mean Target Spherical Equivalent, Preop Keratometric Cylinder and IOL Power Implanted**
**First Eyes - ZLB00 and ZCB00 Control**
**Safety Population**
| Variable | IOL | N | Mean | Std. Dev. | Median | Min. | Max. | Lower 95% Conf. Limit | Upper 95% Conf. Limit | P Value^{a} |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
| Target Spherical Equivalent (D) | ZLB00 | 150 | -0.052 | 0.117 | -0.060 | -0.26 | 0.42 | -0.068 | -0.036 | - |
| ZCB00 | 148 | -0.070 | 0.126 | -0.080 | -0.49 | 0.40 | -0.088 | -0.053 | - |
| Difference | - | 0.018 | - | - | - | - | -0.005 | 0.042 | 0.1932 |
| Keratometric Cylinder (D) | ZLB00 | 150 | 0.493 | 0.253 | 0.500 | 0.00 | 1.00 | 0.459 | 0.528 | - |
| ZCB00 | 148 | 0.543 | 0.266 | 0.570 | 0.00 | 1.09 | 0.507 | 0.579 | - |
| Difference | - | -0.050 | - | - | - | - | -0.099 | -0.000 | 0.0987 |
| IOL Power Implanted (D) | ZLB00 | 150 | 21.550 | 2.475 | 22.000 | 16.00 | 26.00 | 21.215 | 21.885 | - |
| ZCB00 | 148 | 21.044 | 1.992 | 21.000 | 16.00 | 28.00 | 20.773 | 21.315 | - |
| Difference | - | 0.506 | - | - | - | - | 0.077 | 0.935 | 0.0527 |
$^{a}$ P-Value from 2-sided 2-sample t-test
## **D. Safety and Effectiveness Results**
### **1. Safety Results**
The analysis of safety was based on the safety cohort of 297 subjects (147 ZKB00 model, 150 ZLB00 model) implanted with the investigational lenses, and the 441 subjects (145 ZKB00 model, 150 ZLB00 model, 146 ZCB00 control model) available for the 6-month evaluation. The key safety outcomes for this study are presented below in Table 13 to Table 26. Adverse effects are reported in Table 13 and Table 14.
PMA P980040/S049: FDA Summary of Safety and Effectiveness Data
Page 15
{15}
#### **ADVERSE EFFECTS THAT OCCURRED IN THE PMA CLINICAL STUDY:**
Overall, 3.6% (16/445) of subjects experienced adverse events during the study to date; however, only 0.7% (3/445) of subjects (1 ZKB00, 1 ZLB00 and 1 ZCB00) experienced lens-related events, and only one of which was related to the optical/visual properties of the lens (1 ZLB00 lens was removed due to halos; 0.7%, 1/150). A slightly higher incidence of ZLB00 subjects (5.3%; 8/150) experienced adverse events compared to ZKB00 subjects (3.4%; 5/147) or ZCB00 subjects (2.0%; 3/148); however, the events were not lens-related and were generally a result of secondary surgical interventions (SSIs) to treat primary events (endophthalmitis, etc.).
The incidence rates of cumulative adverse events for the ZKB00 and ZLB00 first eyes compared to the ISO SPE rates are presented in Table 13. The incidence rates for the ZKB00 and ZLB00 compared favorably to the specified ISO SPE rates. Only the rate of surgical re-interventions in the ZLB00 group were statistically higher than the FDA grid rate of 0.8% (**p=0.0075** for first and second eyes, respectively). Secondary surgical intervention events for ZKB00 and ZLB00 are specified in Table 14.
PMA P980040/S049: FDA Summary of Safety and Effectiveness Data
Page 16
{16}
**Table 13:**
**6-Month Cumulative Medical Complications/Adverse Events**
**vs. ISO 11979-7 SPEᵃ Rates**
**Safety Population**
| Cumulative Medical Complications/ Adverse Events | ISO SPEᵃ Rate % | ZKB00 | | | | ZLB00 | | | |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
| | | First Eyes N=147 | | Second Eyes N=145 | | First Eyes N=150 | | Second Eyes N=150 | |
| | | n | % | n | % | n | % | n | % |
| Cystoid macular edemaᵇ | 3.0 | 2 | 1.4 | 1 | 0.7 | 0 | 0.0 | 0 | 0.0 |
| Hypopyon | 0.3 | 0 | 0.0 | 0 | 0.0 | 0 | 0.0 | 1 | 0.7ᶜ |
| Endophthalmitis | 0.1 | 0 | 0.0 | 0 | 0.0 | 0 | 0.0 | 1 | 0.7ᵈ |
| Lens dislocated from posterior chamber | 0.1 | 0 | 0.0 | 0 | 0.0 | 0 | 0.0 | 0 | 0.0 |
| Pupillary block | 0.1 | 0 | 0.0 | 0 | 0.0 | 0 | 0.0 | 0 | 0.0 |
| Retinal detachment | 0.3 | 0 | 0.0 | 0 | 0.0 | 0 | 0.0 | 1 | 0.7ᶜ |
| Eyes with secondary surgical intervention | 0.8 | 0 | 0.0 | 3 | 2.1ᵉ | 5ᶠ | 3.3ᵍ | 5ʰ | 3.3ᵍ |
| -Lens related | | 0 | 0.0 | 1 | 0.7 | 1 | 0.7 | 0 | 0.0 |
| -Not lens related | | 0 | 0.0 | 2 | 1.4 | 4ᶠ | 2.7 | 5ʰ | 3.3ᵍ |
ᵃ Per ISO 11979-7 Ophthalmic Implants-Intraocular Lenses (Part 7): The SPE rate is the safety and performance endpoint.
ᵇ Includes all cases of CME, regardless of investigator opinion regarding AE status.
ᶜ Incidence rate is not statistically significantly different than ISO SPE rate (p=0.3628)
ᵈ Incidence rate is not statistically significantly different than ISO SPE rate (p=0.1394)
ᵉ Incidence rate is not statistically significantly different than ISO SPE rate (p=0.1112)
ᶠ One incident was reported after database lock.
ᵍ Incidence rate is statistically significantly different than ISO SPE rate (p=0.0075)
ʰ One of these 5 eyes underwent 3 SSIs for a total of 7 SSI procedures in 5 eyes.
PMA P980040/S049: FDA Summary of Safety and Effectiveness Data
Page 17
{17}
**Secondary Surgical Interventions**
| Secondary Surgical Interventions | ZKB00 | | | | ZLB00 | | | |
| --- | --- | --- | --- | --- | --- | --- | --- | --- |
| | First Eyes N=147 | | Second Eyes N=145 | | First Eyes N=150 | | Second Eyes N=150 | |
| | n | % | n | % | n | % | n | % |
| **Secondary Surgical Interventions:** | | | | | | | | |
| **Lens-Related** | **0** | **0.0** | **1** | **0.7** | **1** | **0.7** | **0** | **0.0** |
| IOL exchange (halos) | 0 | 0.0 | 0 | 0.0 | 1 | 0.7 | 0 | 0.0 |
| IOL repositioning (decentration) | 0 | 0.0 | 1 | 0.7 | 0 | 0.0 | 0 | 0.0 |
| **Secondary Surgical Interventions:** | | | | | | | | |
| **Not Lens-Related** | **0** | **0.0** | **2** | **1.4** | **4** | **2.7** | **5** | **3.3** |
| Blepharoplasty | 0 | 0.0 | 0 | 0.0 | 2 | 1.3 | 2 | 1.3 |
| Retinal repair | 0 | 0.0 | 0 | 0.0 | 0 | 0.0 | 1^{a} | 0.7 |
| Endophthalmitis | | | | | | | | |
| -Retinal detachment | 0 | 0.0 | 0 | 0.0 | 0 | 0.0 | 1 | 0.7 |
| - Retinal tear | 0 | 0.0 | 0 | 0.0 | 1 | 0.7 | 0 | 0.0 |
| Removal of residual cortex | 0 | 0.0 | 1 | 0.7 | 0 | 0.0 | 0 | 0.0 |
| Ruptured globe repair & iridoplasty | 0 | 0.0 | 0 | 0.0 | 0 | 0.0 | 1^{b} | 0.7 |
| Treatment injections for medical complications: | | | | | | | | |
| -Endophthalmitis (with vitreous tap) | 0 | 0.0 | 0 | 0.0 | 0 | 0.0 | 2^{a} | 1.3 |
| -Episcleritis | 0 | 0.0 | 0 | 0.0 | 1 | 0.7 | 0 | 0.0 |
| -Diabetic retinopathy | 0 | 0.0 | 1 | 0.7 | 0 | 0.0 | 0 | 0.0 |
| **TOTAL Eyes** | **0** | **0.0** | **3** | **2.1** | **5** | **3.3** | **5** | **3.3** |
$^{a}$ Same eye.
$^{b}$ Orbital fracture due to fall.
There were no persistent medical complications (0%) present at 6 months for TECNIS® Multifocal IOLs, Models ZKB00 or ZLB00 first or second eyes; therefore, the persistent event rates for the ZKB00 and ZLB00 lens models are below the ISO SPE persistent rates (for corneal edema 0.3%; cystoid macular edema 0.5%; iritis 0.3%; and raised IOP requiring treatment 0.4%).
The safety of the device for multifocal correction of aphakia was not based on this sample alone, but rather on all available data for the device (and the parent IOLs) to date. The safety data from this study were for confirmatory purposes.
Adverse events and complications and their observed rates were generally similar to those seen from studies of similar types of IOLs.
#### Distance Visual Acuity
Distance visual acuities were tested using 100% Early Treatment Diabetic Retinopathy Study (ETDRS) charts at 4.0 meters under photopic conditions (85 cd/m$^{2}$). Table 15 presents monocular distance visual acuity results for ZKB00, ZLB00 and ZCB00 control first-eyes at 6 months. The proportions of first eyes achieving monocular BCDVA of 20/40 or better for the ZKB00 lens group (99.3%) and the ZLB00 lens group (100%) were above the ISO SPE criterion for percent of
PMA P980040/S049: FDA Summary of Safety and Effectiveness Data
Page 18
{18}
eyes with best-corrected distance visual acuity achieving 20/40 or better (92.5%). In addition, the proportions of best-case (Table 16) first eyes achieving monocular BCDVA of 20/40 or better also exceeded the best-case ISO SPE rate (96.87%) for both the ZKB00 group (99.3%) and the ZLB00 group (100%). The distribution of binocular distance visual acuity results for ZKB00, ZLB00 and ZCB00 subjects at 6 months are presented in Table 17.
PMA P980040/S049: FDA Summary of Safety and Effectiveness Data
Page 19
{19}
**Monocular Distance Visual Acuity at 6 Months**
| Visual Acuity LogMAR (Snellen) | ZKB00 (+2.75) N=145 | | | | ZLB00 (+3.25) N=150 | | | | ZCB00 N=146 | | | |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
| | Uncorrected | | Best Corrected | | Uncorrected | | Best Corrected | | Uncorrected | | Best Corrected | |
| | n | % | n | % | N | % | n | % | n | % | n | % |
| 0.0 (20/20 or Better) | 60 | 41.4 | 123 | 84.8 | 60 | 40.0 | 124 | 82.7 | 71 | 48.6 | 128 | 87.7 |
| 0.1 (20/25 or Better) | 102 | 70.3 | 141 | 97.2 | 101 | 67.3 | 141 | 94.0 | 118 | 80.8 | 143 | 97.9 |
| 0.2 (20/32 or Better) | 125 | 86.2 | 144 | 99.3 | 127 | 84.7 | 150 | 100.0 | 131 | 89.7 | 145 | 99.3 |
| 0.3 (20/40 or Better) | 135 | 93.1 | 144 | 99.3 | 144 | 96.0 | 150 | 100.0 | 139 | 95.2 | 146 | 100.0 |
| 0.4-0.6 (20/50-20/80) | 10 | 6.9 | 1 | 0.7 | 6 | 4.0 | 0 | 0.0 | 7 | 4.8 | 0 | 0.0 |
| 0.7 (20/100) or worse | 0 | 0.0 | 0 | 0.0 | 0 | 0.0 | 0 | 0.0 | 0 | 0.0 | 0 | 0.0 |
%=n/Total Tested
**Monocular Best Corrected Distance Visual Acuity at 6 Months**
| Visual Acuity LogMAR (Snellen) | ZKB00 (+2.75) N=144 | ZLB00 (+3.75) N=149 | ZCB00 N=144 |
| --- | --- | --- | --- |
| n | % | n | % | n | % |
| 0.0 (20/20 or Better) | 123 | 85.4 | 124 | 83.2 | 127 | 88.2 |
| 0.1 (20/25 or Better) | 140 | 97.2 | 141 | 94.6 | 141 | 97.9 |
| 0.2 (20/32 or Better) | 143 | 99.3 | 149 | 100.0 | 143 | 99.3 |
| 0.3 (20/40 or Better) | 143 | 99.3 | 149 | 100.0 | 144 | 100.0 |
| 0.4-0.6 (20/50-20/80) | 1 | 0.7 | 0 | 0.0 | 0 | 0.0 |
| 0.7 (20/100) or worse | 0 | 0.0 | 0 | 0.0 | 0 | 0.0 |
%=n/Total Tested
PMA P980040/S049: FDA Summary of Safety and Effectiveness Data
Page 20
{20}
**Binocular Distance Visual Acuity at 6 Months**
| Visual Acuity LogMAR (Snellen) | ZKB00 (+2.75) N=145 | | | | ZLB00 (+3.25) N=150 | | | | ZCB00 N=146 | | | |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
| | Uncorrected | | Best Corrected | | Uncorrected | | Best Corrected | | Uncorrected | | Best Corrected | |
| | n | % | n | % | N | % | n | % | n | % | n | % |
| 0.0 (20/20 or Better) | 105 | 73.4 | 135 | 94.4 | 108 | 72.0 | 141 | 94.0 | 110 | 75.3 | 140 | 95.9 |
| 0.1 (20/25 or Better) | 133 | 93.0 | 142 | 99.3 | 138 | 92.0 | 150 | 100.0 | 133 | 91.1 | 146 | 100.0 |
| 0.2 (20/32 or Better) | 140 | 97.9 | 143 | 100.0 | 148 | 98.7 | 150 | 100.0 | 141 | 96.6 | 146 | 100.0 |
| 0.3 (20/40 or Better) | **142** | **99.3** | **143** | **100.0** | **149** | **99.3** | **150** | **100.0** | **145** | **99.3** | **146** | **100.0** |
| 0.4-0.6 (20/50-20/80) | 1 | 0.7 | 0 | 0.0 | 1 | 0.7 | 0 | 0.0 | 1 | 0.7 | 0 | 0.0 |
| 0.7 (20/100) or worse | 0 | 0.0 | 0 | 0.0 | 0 | 0.0 | 0 | 0.0 | 0 | 0.0 | 0 | 0.0 |
%=n/Total Tested
PMA P980040/S049: FDA Summary of Safety and Effectiveness Data
Page 21
{21}
Table 18 presents mean monocular distance visual acuities at 6 months for ZKB00, ZLB00 and ZCB00 first eyes. Comparison of mean monocular BCDVA to the control lens was one of the key safety endpoints. Non-inferiority testing showed that the upper limit of the 90% confidence intervals of the mean difference in BCDVA between each of the TECNIS® Multifocal IOLs, Models ZKB00 and ZLB00, and the ZCB00 control group to be less than 1.0 line in both cases (LogMAR 0.030, 0.3 lines, for the ZKB00 group vs. the ZCB00 group; and, LogMAR 0.041, 0.4 lines, for the ZLB00 group vs. the ZCB00 group). These results indicate that both the ZKB00 and ZLB00 IOLs are non-inferior to the monofocal control lens in providing distance visual acuity. Table 19 presents mean binocular distance visual acuities at 6 months for ZKB00, ZLB00 and ZCB00 subjects.
**Table 18:**
**Mean Monocular Distance Visual Acuity at 6 Months**
**First Eyes - ZKB00 and ZLB00 vs. ZCB00 Control**
**Safety Population**
| | IOL | N | Mean LogMA R | Snellen Line Equivalent | Std. Dev. | Lower 90% Conf. Limit | Upper 90% Conf. Limit |
| --- | --- | --- | --- | --- | --- | --- | --- |
| **Uncorrected** | **ZKB00** | 145 | 0.102 | 20/25 | 0.136 | 0.083 | 0.121 |
| | **ZCB00** | 146 | 0.078 | 20/25 | 0.134 | 0.060 | 0.097 |
| | **Difference** | - | 0.024 | 0.2 lines | - | -0.002 | 0.050 |
| | **ZLB00** | 150 | 0.112 | 20/25 | 0.131 | 0.094 | 0.130 |
| | **ZCB00** | 146 | 0.078 | 20/25 | 0.134 | 0.060 | 0.097 |
| | **Difference** | - | 0.034 | 0.3 lines | - | 0.008 | 0.059 |
| **Best Corrected** | **ZKB00** | 145 | -0.022 | 20/20 | 0.087 | -0.034 | -0.011 |
| | **ZCB00** | 146 | -0.036 | 20/20 | 0.087 | -0.048 | -0.024 |
| | **Difference** | - | 0.013 | 0.1 lines | - | -0.003 | 0.030^{a} |
| | **ZLB00** | 150 | -0.012 | 20/20 | 0.085 | -0.023 | -0.000 |
| | **ZCB00** | 146 | -0.036 | 20/20 | 0.087 | -0.048 | -0.024 |
| | **Difference** | - | 0.024 | 0.2 lines | - | 0.008 | 0.041^{a} |
$^{a}$ The upper 90% CI is used for non-inferiority comparison due to the mean difference of test minus control with negative LogMAR values.
PMA P980040/S049: FDA Summary of Safety and Effectiveness Data
Page 22
{22}
**Table 19:**
**Mean Binocular Distance Visual Acuity at 6 Months**
**First Eyes - ZKB00 and ZLB00 vs. ZCB00 Control**
**Safety Population**
| | IOL | N | Mean LogMA R | Snellen Line Equivalent | Std. Dev. | Lower 90% Conf. Limit | Upper 90% Conf. Limit |
| --- | --- | --- | --- | --- | --- | --- | --- |
| **Uncorrected** | **ZKB00** | 143 | 0.008 | 20/20 | 0.101 | -0.006 | 0.022 |
| | **ZCB00** | 146 | -0.005 | 20/20 | 0.112 | -0.020 | 0.011 |
| | **Difference** | - | 0.013 | 0.1 lines | - | -0.008 | 0.034 |
| | **ZLB00** | 150 | 0.016 | 20/20 | 0.100 | 0.003 | 0.030 |
| | **ZCB00** | 146 | -0.005 | 20/20 | 0.112 | -0.020 | 0.011 |
| | **Difference** | - | 0.021 | 0.2 lines | - | 0.000 | 0.041 |
| **Best Corrected** | **ZKB00** | 143 | -0.073 | 20/16 | 0.079 | -0.084 | -0.062 |
| | **ZCB00** | 146 | -0.085 | 20/16 | 0.076 | -0.095 | -0.075 |
| | **Difference** | - | 0.012 | 0.1 lines | - | -0.003 | 0.028 |
| | **ZLB00** | 150 | -0.062 | 20/16 | 0.075 | -0.072 | -0.052 |
| | **ZCB00** | 146 | -0.085 | 20/16 | 0.076 | -0.095 | -0.075 |
| | **Difference** | - | 0.023 | 0.2 lines | - | 0.008 | 0.037 |
### *Contrast Sensitivity*
Binocular best corrected distance contrast sensitivity testing was performed using the Vector Vision ETDRS light box and contrast sensitivity charts under three lighting conditions: mesopic without glare (Table 20), mesopic with glare (Table 21), and photopic with glare (Table 22). As expected with multifocality, median contrast scores for both the ZKB00 and ZLB00 multifocal subject groups were somewhat reduced compared to the monofocal control group under each lighting condition and spatial frequency (Table 20 - Table 22). The most challenging condition was mesopic lighting with glare as median scores were slightly lower for all IOL groups and median differences between IOL groups were the most prominent. However, with the exception of the mesopic 12 cpd conditions, median differences between IOL groups were generally within -0.15 log units. The largest median differences were between the ZKB00 (+2.75 add) multifocal lens and the ZCB00 monofocal control lens (-0.250 and -0.255 for the 12 cpd mesopic without glare and mesopic with glare conditions, respectively). Assignment of reference patch scores to unmeasurable values would bias the mean values higher and parametric variability estimates lower. The medians (50th percentile values) in Table 20 - Table 22 are unbiased, because less than 25% of the values were unmeasurable (i.e., subjects not seeing the reference pattern) for any condition. The 25th and 75th percentiles are also reported to give unbiased estimates of the variability of the results. In addition, no appreciable pupil-size effects were seen when results were analyzed by pupil size; this was expected due to the optic design of the TECNIS® Multifocal IOLs.
PMA P980040/S049: FDA Summary of Safety and Effectiveness Data
Page 23
{23}
Table 20:
Contrast Sensitivityᵃ at 6 Months Mesopic Without Glare
| Spatial Frequency | Lens Model | N | Mesopic Without Glare | | | | |
| --- | --- | --- | --- | --- | --- | --- | --- |
| | | | 25^{th} percentile | Median^{b} 50^{th} percentile | 75^{th} percentile | Subjects who did not see the reference pattern^{a} | |
| | | | | | | n | % |
| **1.5 cpd** | ZKB00 (+2.75) | 143 | 1.445 | 1.595 | 1.745 | 0 | 0.0 |
| | ZLB00 (+3.25) | 150 | 1.370 | 1.595 | 1.745 | 0 | 0.0 |
| | ZCB00 | 146 | 1.520 | 1.670 | 1.745 | 0 | 0.0 |
| **3.0 cpd** | ZKB00 (+2.75) | 143 | 1.415 | 1.635 | 1.780 | 0 | 0 |
| | ZLB00 (+3.25) | 150 | 1.485 | 1.705 | 1.855 | 0 | 0.0 |
| | ZCB00 | 146 | 1.415 | 1.630 | 1.780 | 1 | 0.7 |
| **6.0 cpd** | ZKB00 (+2.75) | 143 | 1.380 | 1.625 | 1.700 | 5 | 3.5 |
| | ZLB00 (+3.25) | 150 | 1.380 | 1.550 | 1.770 | 3 | 2.0 |
| | ZCB00 | 146 | 1.465 | 1.700 | 1.770 | 3 | 2.1 |
| **12.0 cpd** | ZKB00 (+2.75) | 143 | 0.610 | 0.995 | 1.250 | 17 | 11.9 |
| | ZLB00 (+3.25) | 150 | 0.760 | 1.080 | 1.395 | 17 | 11.3 |
| | ZCB00 | 146 | 0.995 | 1.245 | 1.470 | 13 | 8.9 |
ᵃ All subjects analyzed; Note: reference scores assigned for subjects who did not see the reference pattern for a spatial frequency.
ᵇ Log₁₀(Contrast⁻¹).
PMA P980040/S049: FDA Summary of Safety and Effectiveness Data
Page 24
{24}
Table 21:
Contrast Sensitivityᵃ at 6 Months Mesopic With Glare
| Spatial Frequency | Lens Model | N | Mesopic With Glare | | | Subjects who did not see the reference patternᵃ | |
| --- | --- | --- | --- | --- | --- | --- | --- |
| | | | 25ᵗʰ percentile | Medianᵇ 50ᵗʰ percentile | 75ᵗʰ percentile | n | % |
| **1.5 cpd** | ZKB00 (+2.75) | 143 | 1.370 | 1.595 | 1.745 | 1 | 0.7 |
| | ZLB00 (+3.25) | 150 | 1.370 | 1.595 | 1.820 | 0 | 0.0 |
| | ZCB00 | 146 | 1.445 | 1.670 | 1.745 | 0 | 0.0 |
| **3.0 cpd** | ZKB00 (+2.75) | 143 | 1.415 | 1.560 | 1.780 | 1 | 0.7 |
| | ZLB00 (+3.25) | 150 | 1.490 | 1.705 | 1.855 | 1 | 0.7 |
| | ZCB00 | 146 | 1.490 | 1.630 | 1.780 | 0 | 0.0 |
| **6.0 cpd** | ZKB00 (+2.75) | 143 | 1.380 | 1.550 | 1.700 | 9 | 6.3 |
| | ZLB00 (+3.25) | 150 | 1.380 | 1.625 | 1.700 | 6 | 4.0 |
| | ZCB00 | 146 | 1.465 | 1.700 | 1.840 | 3 | 2.1 |
| **12.0 cpd** | ZKB00 (+2.75) | 143 | 0.610 | 0.995 | 1.325 | 26 | 18.2 |
| | ZLB00 (+3.25) | 150 | 0.610 | 1.080 | 1.375 | 22 | 14.7 |
| | ZCB00 | 146 | 0.910 | 1.250 | 1.540 | 13 | 8.9 |
ᵃ All subjects analyzed; Note: reference scores assigned for subjects who did not see the reference pattern for a spatial frequency.
ᵇ Log₁₀(Contrast⁻¹).
PMA P980040/S049: FDA Summary of Safety and Effectiveness Data
Page 25
{25}
Table 22:
Contrast Sensitivityᵃ at 6 Months Photopic With Glare
| Spatial Frequency | Lens Model | N | Photopic With Glare | | | Subjects who did not see the reference patternᵃ | |
| --- | --- | --- | --- | --- | --- | --- | --- |
| | | | 25ᵗʰ percentile | Medianᵇ 50ᵗʰ percentile | 75ᵗʰ percentile | n | % |
| **3.0 cpd** | ZKB00 (+2.75) | 143 | 1.485 | 1.705 | 1.780 | 1 | 0.7 |
| | ZLB00 (+3.25) | 150 | 1.490 | 1.705 | 1.855 | 1 | 0.7 |
| | ZCB00 | 146 | 1.630 | 1.743 | 1.855 | 0 | 0.0 |
| **6.0 cpd** | ZKB00 (+2.75) | 143 | 1.625 | 1.770 | 1.915 | 4 | 2.8 |
| | ZLB00 (+3.25) | 150 | 1.625 | 1.770 | 1.990 | 5 | 3.3 |
| | ZCB00 | 146 | 1.770 | 1.915 | 2.065 | 2 | 1.4 |
| **12.0 cpd** | ZKB00 (+2.75) | 143 | 1.165 | 1.400 | 1.615 | 7 | 4.9 |
| | ZLB00 (+3.25) | 150 | 1.250 | 1.470 | 1.690 | 9 | 6.0 |
| | ZCB00 | 146 | 1.325 | 1.540 | 1.690 | 8 | 5.5 |
| **18.0 cpd** | ZKB00 (+2.75) | 143 | 0.640 | 0.960 | 1.180 | 9 | 6.3 |
| | ZLB00 (+3.25) | 150 | 0.725 | 0.995 | 1.175 | 14 | 9.3 |
| | ZCB00 | 146 | 0.885 | 1.100 | 1.250 | 9 | 6.2 |
ᵃ All subjects analyzed; Note: reference scores assigned for subjects who did not see the reference pattern for a spatial frequency.
ᵇ Log₁₀(Contrast⁻¹).
PMA P980040/S049: FDA Summary of Safety and Effectiveness Data
Page 26
{26}
### General Medical and Lens Findings
Medical and lens findings in this study were typical and within expected ranges for the TECNIS® Multifocal IOLs, Models ZKB00 and ZLB00, as well as the TECNIS® ZCB00 monofocal control IOL. The most reported finding at 6 months was posterior capsule opacification (PCO) for all three lens types (29%-37%) with the majority of reports noted as “trace”. General medical and lens findings for the TECNIS® Multifocal IOLs were comparable to the monofocal control IOL, indicating that the difference in optical surface design for the TECNIS® Multifocal IOLs does not impact the safety of the lens with respect to general medical outcomes.
### Fundus Visualization
At the 6-month study visit, investigators evaluated the ability to visualize the fundus during the dilated fundus exams. In all cases (100%; 145/145 ZKB00 (+2.75), 150/150 ZLB00 (+3.25) multifocal first eyes and 146/146 ZCB00 monofocal first eyes), fundus visualization was deemed “adequate.” During the study, no difficulties were reported in evaluating or treating retinal complications in multifocal eyes; however, only three multifocal eyes underwent a surgical retinal procedure in this study.
### Optical/Visual Symptoms
Table 23 provides a summary of patient questionnaire results (directed reports) concerning difficulties with visual problems. The most reported symptom/difficulty was for halos for the TECNIS® Multifocal IOLs, Models ZKB00 and ZLB00 compared to the TECNIS® 1-Piece monofocal control IOL, Model ZCB00, as might be expected. Optical/visual symptoms spontaneously reported by subjects (non-directed reports) are presented in Table 24. These non-directed reports are typically noted with lower incidences than when subjects are specifically asked about difficulties with visual problems via the questionnaire.
Table 25 presents the trouble with glare reported when driving toward the sun or oncoming headlights. Higher incidence/difficulty was noted for ZLB00 subjects compared to ZKB00 subjects, in line with the higher amount of add power in each multifocal IOL (+2.75 D for the ZKB00 IOL vs. +3.25 D for the ZLB00 IOL). Nevertheless, directed reports of severe difficulty with halos for either the ZKB00 IOL (5.6%) or the ZLB00 IOL (10.7%) at 6 months are within that of the original TECNIS® Multifocal IOL, Model ZM900, at 1 year (18.3%). Similarly, non-directed responses of severe halos for ZKB00 first eyes (0.7%) and ZLB00 first eyes (4.0%) at 6 months are also within that of the original TECNIS® Multifocal IOL, Model ZM900, at 1 year (5.4%).
PMA P980040/S049: FDA Summary of Safety and Effectiveness Data
Page 27
{27}
**Table 23:**
**Degree of Difficulty with Night Vision, Glare/Flare and Halos at 6 Months**
**(Directed Reports from a Questionnaire; Scale of 1-7)**
**(With Glasses if You Need Them)**
| | Safety Population | | | | | |
| --- | --- | --- | --- | --- | --- | --- |
| | ZKB00 N=142 | | ZLB00 N=149 | | ZCB00 N=145 | |
| | n | % | n | % | n | % |
| **Night Vision** | | | | | | |
| No difficulty (1, 2) | 129 | 90.8 | 125 | 83.9 | 125 | 86.2 |
| Moderate difficulty (3, 4, 5) | 12 | 8.5 | 20 | 13.4 | 14 | 9.7 |
| Severe difficulty (6, 7) | 1 | 0.7 | 4 | 2.7 | 6 | 4.1 |
| **Glare/Flare** | | | | | | |
| No difficulty (1, 2) | 109 | 76.8 | 103 | 69.1 | 117 | 80.7 |
| Moderate difficulty (3, 4, 5) | 31 | 21.8 | 38 | 25.5 | 18 | 12.4 |
| Severe difficulty (6, 7) | 2 | 1.4 | 8 | 5.4 | 10 | 6.9 |
| **Halos** | | | | | | |
| No difficulty (1, 2) | 98 | 69.0 | 85 | 57.0 | 122 | 84.1 |
| Moderate difficulty (3, 4, 5) | 36 | 25.4 | 48 | 32.2 | 20 | 13.8 |
| Severe difficulty (6, 7) | 8 | 5.6 | 16 | 10.7 | 3 | 2.1 |
%=n/N
PMA P980040/S049: FDA Summary of Safety and Effectiveness Data
Page 28
{28}
**Non-Directed Reports of Ocular Symptoms (First Eyes) at 6 Months**
| Ocular Symptoms | ZKB00 N=145 | | ZLB00 N=150 | | ZCB00 N=146 | |
| --- | --- | --- | --- | --- | --- | --- |
| | n | % | n | % | n | % |
| **Image Quality** | | | | | | |
| Blurred vision | 28 | 19.3 | 25 | 16.7 | 38 | 26.0 |
| - Overall | 4 | 2.8 | 7 | 4.7 | 2 | 1.4 |
| - Distance | 5 | 3.4 | 2 | 1.3 | 3 | 2.1 |
| - Intermediate | 3 | 2.1 | 3 | 2.0 | 2 | 1.4 |
| - Near | 18 | 12.4 | 14 | 9.3 | 33 | 22.6 |
| **Optical/Visual** | | | | | | |
| Halos | 29 | 20.0 | 37 | 24.7 | 6 | 4.1 |
| - Mild | 20 | 13.8 | 20 | 13.3 | 4 | 2.7 |
| - Moderate | 8 | 5.5 | 11 | 7.3 | 2 | 1.4 |
| - Severe | 1 | 0.7 | 6 | 4.0 | 0 | 0.0 |
| Night Glare | 7 | 4.8 | 8 | 5.3 | 2 | 1.4 |
| - Mild | 5 | 3.4 | 2 | 1.3 | 1 | 0.7 |
| - Moderate | 2 | 1.4 | 3 | 2.0 | 1 | 0.7 |
| - Severe | 0 | 0.0 | 3 | 2.0 | 0 | 0.0 |
| Starbursts | 3 | 2.1 | 6 | 4.0 | 0 | 0.0 |
| - Mild | 1 | 0.7 | 3 | 2.0 | 0 | 0.0 |
| - Moderate | 2 | 1.4 | 1 | 0.7 | 0 | 0.0 |
| - Severe | 0 | 0.0 | 2 | 1.3 | 0 | 0.0 |
| Night vision difficulty (overall) | 0 | 0.0 | 4 | 2.7 | 2 | 1.4 |
| **Sensation** | | | | | | |
| Irritated/itchy/scratchy/burning/gritty | 7 | 4.8 | 20 | 13.3 | 13 | 8.9 |
| Dryness | 16 | 11.0 | 22 | 14.7 | 18 | 12.3 |
Note: Includes reports of symptoms common to multifocal IOLs (halos, night glare, starbursts, and night vision difficulties) as well as any findings reported with an incidence of 10% or more at 6 months.
%=n/N
PMA P980040/S049: FDA Summary of Safety and Effectiveness Data
Page 29
{29}
**Degree$^{a}$ of Trouble with Glare at 6 Months**
| | ZKB00 N=142 | | ZLB00 N=149 | | ZCB00 N=145 | |
| --- | --- | --- | --- | --- | --- | --- |
| | n | % | n | % | n | % |
| **Driving towards the sun** | | | | | | |
| No trouble at all (0) | 84 | 60.0 | 94 | 65.3 | 87 | 61.7 |
| A little bit of trouble (1) | 24 | 17.1 | 16 | 11.1 | 23 | 16.3 |
| Moderate trouble (2) | 20 | 14.3 | 18 | 12.5 | 17 | 12.1 |
| Considerable trouble (3) | 10 | 7.1 | 12 | 8.3 | 11 | 7.8 |
| Major or overwhelming trouble (4) | 2 | 1.4 | 4 | 2.8 | 3 | 2.1 |
| I do not perform this activity for reasons unrelated to my vision (5) | 2 | - | 5 | - | 3 | - |
| Not reported | 0 | - | 0 | - | 1 | - |
| **Driving toward oncoming headlights** | | | | | | |
| No trouble at all (0) | 70 | 51.9 | 66 | 48.5 | 84 | 64.1 |
| A little bit of trouble (1) | 30 | 22.2 | 30 | 22.1 | 22 | 16.8 |
| Moderate trouble (2) | 19 | 14.1 | 23 | 16.9 | 13 | 9.9 |
| Considerable trouble (3) | 13 | 9.6 | 13 | 9.6 | 8 | 6.1 |
| Major or overwhelming trouble (4) | 3 | 2.2 | 4 | 2.9 | 4 | 3.1 |
| I do not perform this activity for reasons unrelated to my vision (5) | 7 | - | 13 | - | 13 | - |
| Not reported | 0 | - | 0 | - | 1 | - |
%=n/N excluding Not reported and Do Not Perform this activity.
$^{a}$ On a scale of 0-4 (5 = I do not perform this activity for reasons unrelated to my vision)
Table 26 presents the rating of the quality of near and far vision while indoors. Over 90% of subjects reported good vision indoors overall; however, fewer multifocal subjects reported good vision while indoors under dim lighting.
The questionnaire administered was not validated according to FDA’s guidance document entitled “Patient-reported outcome measures: use in medical product development to support labeling claims”, dated December 2009.
PMA P980040/S049: FDA Summary of Safety and Effectiveness Data
Page 30
{30}
**Rating of the Quality$^{a}$ (Sharpness, Clarity) of Near and Far Vision at 6 Months**
| | Near Vision | | | | | | Far Vision | | | | | |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
| | ZKB00 N=142 | | ZLB00 N=149 | | ZCB00 N=145 | | ZKB00 N=142 | | ZLB00 N=149 | | ZCB00 N=145 | |
| | n | % | n | % | n | % | n | % | n | % | n | % |
| **Indoors** | | | | | | | | | | | | |
| Poor Vision (1,2) | 0 | 0.0 | 1 | 0.7 | 2 | 1.4 | 0 | 0.0 | 0 | 0.0 | 0 | 0.0 |
| Fair Vision (3,4,5) | 12 | 8.5 | 9 | 6.0 | 9 | 6.2 | 8 | 5.6 | 8 | 5.4 | 8 | 5.5 |
| Good Vision (6,7) | 130 | 91.5 | 139 | 93.3 | 134 | 92.4 | 134 | 94.4 | 140 | 94.6 | 137 | 94.5 |
| Not Reported | 0 | - | 0 | - | 0 | - | 0 | - | 1 | - | 0 | - |
| **Indoors with dim lighting** | | | | | | | | | | | | |
| Poor Vision (1,2) | 3 | 2.1 | 2 | 1.3 | 2 | 1.4 | 0 | 0.0 | 1 | 0.7 | 0 | 0.0 |
| Fair Vision (3,4,5) | 48 | 33.8 | 53 | 35.6 | 35 | 24.1 | 27 | 19.0 | 29 | 19.7 | 20 | 13.8 |
| Good Vision (6,7) | 91 | 64.1 | 94 | 63.1 | 108 | 74.5 | 115 | 81.0 | 117 | 79.6 | 125 | 86.2 |
| Not Reported | 0 | - | 0 | - | 0 | - | 0 | - | 2 | - | 0 | - |
%=n/N excluding Not Reported
$^{a}$ On a scale of 1-7
## 2. Effectiveness Results
The analysis of effectiveness was based primarily on the acuity data evaluable at the 6 month time point. Key effectiveness outcomes are presented in Table 27 to Table 35 and Figure 1 to Figure 4.
### Near Visual Acuities
Near visual acuities were tested using 100% ETDRS near charts at the fixed test distance of 40 cm and at the subjects’ best test distance, with and without distance correction under photopic (85 cd/m$^{2}$) lighting conditions and with distance correction under mesopic (3 cd/m$^{2}$) lighting conditions.
The primary effectiveness endpoint of improved mean, monocular, photopic distance-corrected near visual acuity (DCNVA) at 40 cm was achieved for both TECNIS® Multifocal IOLs, Models ZKB00 and ZLB00, with statistically significant improvements (p<0.0001) in mean DCNVA at 6 months vs. the control IOL. Model ZKB00 (+2.75 D add power) was found to have a statistically significant improvement (p<0.0001) of 3.3 lines of monocular DCNVA over the control IOL (Table 27) while Model ZLB00 (+3.25 D add power) was found to have a statistically significant improvement (p<0.0001) of 4.0 lines of monocular DCNVA over the control IOL (Table 27) when tested at 40 cm. For the primary analysis group of the ITT population, results were also statistically significant (p<0.0001) with similar improvements in favor of the TECNIS® Multifocal IOLs, Models ZKB00 and ZLB00.
PMA P980040/S049: FDA Summary of Safety and Effectiveness Data
Page 31
{31}
**Table 27:**
**Mean Monocular Distance Corrected Near Visual Acuity at 40 cm at 6 Months**
**First Eyes - ZKB00 and ZLB00 vs. ZCB00 Control**
**Safety Population**
| IOL | N | Mean LogMAR | Snellen Line Equivalent | Std. Dev. | Lower 95% Conf. Limit | Upper 95% Conf. Limit | P Value^{a} |
| --- | --- | --- | --- | --- | --- | --- | --- |
| ZKB00 | 145 | 0.252 | 20/40 | 0.143 | 0.229 | 0.276 | |
| ZCB00 | 146 | 0.582 | 20/80 | 0.166 | 0.555 | 0.609 | |
| **Difference** | | **-0.329** | **-3.3 lines** | - | -0.365 | -0.294 | **<0.0001** |
| ZLB00 | 150 | 0.179 | 20/32 | 0.129 | 0.158 | 0.200 | |
| ZCB00 | 146 | 0.582 | 20/80 | 0.166 | 0.555 | 0.609 | |
| **Difference** | | **-0.403** | **-4.0 lines** | - | -0.437 | -0.369 | **<0.0001** |
$^{a}$ P value from 1-sided 2-sample t-test
Mean outcomes for all monocular and binocular near visual acuities tested at 6 months for the ZKB00, ZLB00 and ZCB00 lens groups are presented in Table 28. In all cases, mean visual acuity outcomes at 6 months were improved for the TECNIS® Multifocal IOLs, Models ZKB00 and ZLB00, by 3 to 4 lines compared to the control IOL, similar to outcomes for the primary study endpoint of DCNVA at 40 cm. Overall, the various near visual acuity results demonstrate the effectiveness of the TECNIS® Multifocal IOL, Models ZKB00 (+2.75) and ZLB00 (+3.25) in providing substantial near vision compared to the monofocal control lens.
PMA P980040/S049: FDA Summary of Safety and Effectiveness Data
Page 32
{32}
**Mean Near Visual Acuity at 6 Months**
| Near Visual Acuity | Test Distance | Lens Group | Monocular | | | | Binocular | | | |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
| | | | N | Mean LogMAR | Snellen Line Equiv. | Line Gain vs. ZCB00 | N | Mean LogMAR | Snellen Line Equiv. | Line Gain vs. ZCB00 |
| **Uncorrected (Photopic)** | 40 cm | ZKB00 (+2.75) | 145 | 0.238 | 20/32 | 3.3 | 143 | 0.135 | 20/25 | 3.1 |
| | | ZLB00 (+3.25) | 150 | 0.185 | 20/32 | 3.8 | 150 | 0.097 | 20/25 | 3.5 |
| | | ZCB00 | 146 | 0.568 | 20/80 | | 146 | 0.443 | 20/50 | |
| | Best^{a} | ZKB00 (+2.75) | 145 | 0.148 | 20/25 | 3.3 | 143 | 0.079 | 20/25 | 2.7 |
| | | ZLB00 (+3.25) | 150 | 0.141 | 20/25 | 3.3 | 150 | 0.068 | 20/25 | 2.8 |
| | | ZCB00 | 146 | 0.476 | 20/63 | | 146 | 0.346 | 20/40 | |
| **Distance Corrected^{b} (Photopic)** | 40 cm | ZKB00 (+2.75) | 145 | 0.252^{b} | 20/40 | 3.3 | 143 | 0.170 | 20/32 | 3.2 |
| | | ZLB00 (+3.25) | 150 | 0.179^{b} | 20/32 | 4.0 | 150 | 0.106 | 20/25 | 3.8 |
| | | ZCB00 | 146 | 0.582 | 20/80 | | 146 | 0.488 | 20/63 | |
| | Best^{a} | ZKB00 (+2.75) | 145 | 0.154 | 20/32 | 3.5 | 143 | 0.093 | 20/25 | 3.2 |
| | | ZLB00 (+3.25) | 150 | 0.141 | 20/25 | 3.6 | 150 | 0.077 | 20/25 | 3.3 |
| | | ZCB00 | 146 | 0.503 | 20/63 | | 146 | 0.408 | 20/50 | |
| **Distance Corrected Mesopic** | 40 cm | ZKB00 (+2.75) | 145 | 0.447 | 20/50 | 3.3 | 143 | 0.362 | 20/50 | 3.4 |
| | | ZLB00 (+3.25) | 150 | 0.375 | 20/50 | 4.0 | 150 | 0.282 | 20/40 | 4.2 |
| | | ZCB00 | 146 | 0.773 | 20/126 | | 146 | 0.698 | 20/100 | |
| | Best^{a} | ZKB00 (+2.75) | 145 | 0.367 | 20/50 | 3.2 | 143 | 0.292 | 20/40 | 3.3 |
| | | ZLB00 (+3.25) | 150 | 0.330 | 20/40 | 3.6 | 150 | 0.259 | 20/40 | 3.6 |
| | | ZCB00 | 146 | 0.692 | 20/100 | | 146 | 0.624 | 20/80 | |
$^{a}$ Best test distance is the distance at which the subject can read the smallest letters with the most ease.
$^{b}$ The primary study endpoint was photopic distance corrected near VA for first eyes. ZKB00 & ZLB00 showed statistically significantly better VA compared to ZCB00 with **p <0.0001** (from one sided two sample t-test).
Table 29, Table 30, and Table 31 present the distributions of monocular UCNVA, DCNVA and mesopic DCNVA at 6 months for ZKB00, ZLB00 and ZCB00 first eyes. Table 32, Table 33, and Table 34 present the distributions of binocular UCNVA, DCNVA and mesopic DCNVA at 6 months for ZKB00, ZLB00 and ZCB00 subjects.
PMA P980040/S049: FDA Summary of Safety and Effectiveness Data
Page 33
{33}
**Table 29:**
**Monocular Uncorrected Near Visual Acuity at 6 Months**
**First Eyes - ZKB00, ZLB00 and ZCB00 Control**
**Safety Population**
| Visual Acuity | ZKB00 (+2.75) | ZLB00 (+3.25) | ZCB00 |
| --- | --- | --- | --- |
| 40 cm N=145 | Best N=145 | 40 cm N=150 | Best N=150 | 40 cm N=146 | Best N=146 |
| LogMAR (Snellen) | n | % | n | % | n | % | n | % | n | % | n | % |
| 0.0 (20/20 or Better) | 11 | 7.6 | 25 | 17.2 | 21 | 14.0 | 30 | 20.0 | 0 | 0.0 | 0 | 0.0 |
| 0.1 (20/25 or Better) | 44 | 30.3 | 76 | 52.4 | 74 | 49.3 | 123 | 82.0 | 1 | 0.7 | 6 | 4.1 |
| 0.2 (20/32 or Better) | 89 | 61.4 | 119 | 82.1 | 109 | 72.7 | 127 | 84.7 | 5 | 3.4 | 19 | 13.0 |
| 0.3 (20/40 or Better) | **112** | **77.2** | **135** | **93.1** | **132** | **88.0** | **140** | **93.3** | **26** | **17.8** | **44** | **30.1** |
| 0.4-0.6 (20/50-20/80) | 31 | 21.4 | 10 | 6.9 | 17 | 11.3 | 10 | 6.7 | 67 | 45.9 | 72 | 49.3 |
| 0.7 (20/100) or worse | 2 | 1.4 | 0 | 0.0 | 1 | 0.7 | 0 | 0.0 | 53 | 36.3 | 30 | 20.5 |
%=n/Total Tested
**Table 30:**
**Monocular Distance Corrected Near Visual Acuity at 6 Months**
**First Eyes - ZKB00, ZLB00 and ZCB00 Control**
**Safety Population**
| Visual Acuity | ZKB00 (+2.75) | ZLB00 (+3.25) | ZCB00 |
| --- | --- | --- | --- |
| 40 cm N=145 | Best N=145 | 40 cm N=150 | Best N=150 | 40 cm N=146 | Best N=146 |
| LogMAR (Snellen) | n | % | n | % | n | % | n | % | n | % | n | % |
| 0.0 (20/20 or Better) | 10 | 6.9 | 31 | 21.4 | 19 | 12.7 | 39 | 26.0 | 0 | 0.0 | 0 | 0.0 |
| 0.1 (20/25 or Better) | 38 | 26.2 | 73 | 50.3 | 77 | 51.3 | 87 | 58.0 | 1 | 0.7 | 3 | 2.1 |
| 0.2 (20/32 or Better) | 74 | 51.0 | 110 | 75.9 | 113 | 75.3 | 123 | 82.0 | 6 | 4.1 | 11 | 7.5 |
| 0.3 (20/40 or Better) | **116** | **80.0** | **136** | **93.8** | **136** | **90.7** | **136** | **90.7** | **16** | **11.0** | **25** | **17.1** |
| 0.4-0.6 (20/50-20/80) | 27 | 18.6 | 9 | 6.2 | 14 | 9.3 | 14 | 9.3 | 83 | 56.8 | 95 | 65.1 |
| 0.7 (20/100) or worse | 2 | 1.4 | 0 | 0.0 | 0 | 0.0 | 0 | 0.0 | 47 | 32.2 | 26 | 17.8 |
%=n/Total Tested
PMA P980040/S049: FDA Summary of Safety and Effectiveness Data
Page 34
{34}
**Table 31:**
**Monocular Mesopic Distance Corrected Near Visual Acuity at 6 Months**
**First Eyes - ZKB00, ZLB00 and ZCB00 Control**
**Safety Population**
| Visual Acuity | ZKB00 (+2.75) | ZLB00 (+3.25) | ZCB00 |
| --- | --- | --- | --- |
| 40 cm N=145 | Best N=145 | 40 cm N=150 | Best N=150 | 40 cm N=146 | Best N=146 |
| LogMAR (Snellen) | n | % | n | % | n | % | n | % | n | % | n | % |
| 0.0 (20/20 or Better) | 0 | 0.0 | 1 | 0.7 | 2 | 1.3 | 3 | 2.0 | 0 | 0.0 | 0 | 0.0 |
| 0.1 (20/25 or Better) | 3 | 2.1 | 12 | 8.3 | 17 | 11.3 | 28 | 18.7 | 0 | 0.0 | 0 | 0.0 |
| 0.2 (20/32 or Better) | 15 | 10.3 | 40 | 27.6 | 39 | 26.0 | 62 | 41.3 | 0 | 0.0 | 0 | 0.0 |
| 0.3 (20/40 or Better) | 46 | 31.7 | 74 | 51.0 | 74 | 49.3 | 90 | 60.0 | 0 | 0.0 | 1 | 0.7 |
| 0.4-0.6 (20/50-20/80) | 88 | 60.7 | 63 | 43.4 | 62 | 41.3 | 46 | 30.7 | 34 | 23.3 | 58 | 39.7 |
| 0.7 (20/100) or worse | 11 | 7.6 | 8 | 5.5 | 14 | 9.3 | 14 | 9.3 | 112 | 76.7 | 87 | 59.6 |
%=n/Total Tested
**Table 32:**
**Binocular Uncorrected Near Visual Acuity at 6 Months**
**ZKB00, ZLB00 and ZCB00 Control**
**Safety Population**
| Visual Acuity | ZKB00 (+2.75) | ZLB00 (+3.25) | ZCB00 |
| --- | --- | --- | --- |
| 40 cm N=143 | Best N=143 | 40 cm N=150 | Best N=150 | 40 cm N=146 | Best N=146 |
| LogMAR (Snellen) | n | % | n | % | n | % | n | % | n | % | n | % |
| 0.0 (20/20 or Better) | 35 | 24.5 | 57 | 39.9 | 52 | 34.7 | 64 | 42.7 | 0 | 0.0 | 6 | 4.1 |
| 0.1 (20/25 or Better) | 91 | 63.6 | 107 | 74.8 | 118 | 78.7 | 123 | 82.0 | 6 | 4.1 | 16 | 11.0 |
| 0.2 (20/32 or Better) | 120 | 83.9 | 133 | 93.0 | 142 | 94.7 | 145 | 96.7 | 23 | 15.8 | 48 | 32.9 |
| 0.3 (20/40 or Better) | 136 | 95.1 | 141 | 98.6 | 148 | 98.7 | 149 | 99.3 | 49 | 33.6 | 74 | 50.7 |
| 0.4-0.6 (20/50-20/80) | 7 | 4.9 | 2 | 1.4 | 2 | 1.3 | 1 | 0.7 | 83 | 56.8 | 66 | 45.2 |
| 0.7 (20/100) or worse | 0 | 0.0 | 0 | 0.0 | 0 | 0.0 | 0 | 0.0 | 14 | 9.6 | 6 | 4.1 |
%=n/Total Tested
PMA P980040/S049: FDA Summary of Safety and Effectiveness Data
Page 35
{35}
**Table 33:**
**Binocular Distance Corrected Near Visual Acuity at 6 Months**
**ZKB00, ZLB00 and ZCB00 Control**
**Safety Population**
| Visual Acuity | ZKB00 (+2.75) | ZLB00 (+3.25) | ZCB00 |
| --- | --- | --- | --- |
| 40 cm N=143 | Best N=143 | 40 cm N=150 | Best N=150 | 40 cm N=146 | Best N=146 |
| LogMAR (Snellen) | n | % | n | % | n | % | n | % | n | % | n | % |
| 0.0 (20/20 or Better) | 16 | 11.2 | 43 | 30.1 | 47 | 31.3 | 56 | 37.3 | 0 | 0.0 | 2 | 1.4 |
| 0.1 (20/25 or Better) | 72 | 50.3 | 108 | 75.5 | 111 | 74.0 | 120 | 80.0 | 2 | 1.4 | 6 | 4.1 |
| 0.2 (20/32 or Better) | 109 | 76.2 | 133 | 93.0 | 136 | 90.7 | 135 | 90.0 | 10 | 6.8 | 18 | 12.3 |
| 0.3 (20/40 or Better) | **139** | **97.2** | **142** | **99.3** | **146** | **97.3** | **148** | **98.7** | **34** | **23.3** | **55** | **37.7** |
| 0.4-0.6 (20/50-20/80) | 4 | 2.8 | 1 | 0.7 | 4 | 2.7 | 2 | 1.3 | 88 | 60.3 | 77 | 52.7 |
| 0.7 (20/100) or worse | 0 | 0.0 | 0 | 0.0 | 0 | 0.0 | 0 | 0.0 | 24 | 16.4 | 14 | 9.6 |
%=n/Total Tested
**Table 34:**
**Binocular Mesopic Distance Corrected Near Visual Acuity at 6 Months**
**ZKB00, ZLB00 and ZCB00 Control**
**Safety Population**
| Visual Acuity | ZKB00 (+2.75) | ZLB00 (+3.25) | ZCB00 |
| --- | --- | --- | --- |
| 40 cm N=143 | Best N=143 | 40 cm N=150 | Best N=150 | 40 cm N=146 | Best N=146 |
| LogMAR (Snellen) | n | % | n | % | n | % | n | % | n | % | n | % |
| 0.0 (20/20 or Better) | 1 | 0.7 | 3 | 2.1 | 11 | 7.3 | 19 | 12.7 | 0 | 0.0 | 1 | 0.7 |
| 0.1 (20/25 or Better) | 9 | 6.3 | 24 | 16.8 | 40 | 26.7 | 47 | 31.3 | 0 | 0.0 | 1 | 0.7 |
| 0.2 (20/32 or Better) | 34 | 23.8 | 65 | 45.5 | 77 | 51.3 | 89 | 59.3 | 1 | 0.7 | 1 | 0.7 |
| 0.3 (20/40 or Better) | **73** | **51.0** | **103** | **72.0** | **104** | **69.3** | **113** | **75.3** | **2** | **1.4** | **12** | **8.2** |
| 0.4-0.6 (20/50-20/80) | 64 | 44.7 | 34 | 23.8 | 37 | 24.7 | 29 | 19.3 | 61 | 41.8 | 70 | 47.9 |
| 0.7 (20/100) or worse | 6 | 4.2 | 6 | 4.2 | 9 | 6.0 | 8 | 5.3 | 83 | 56.8 | 64 | 43.8 |
%=n/Total Tested
PMA P980040/S049: FDA Summary of Safety and Effectiveness Data
Page 36
{36}
### Defocus Testing
Defocus curve testing was performed on a subset of approximately 60 subjects from each lens group at the 6-month study exam to evaluate binocular best corrected distance visual acuity defocus curves, and any effects of pupil size. The substudy was a non-randomized, modified parallel-group comparison of the binocular best corrected visual acuity depth of focus. Results were also analyzed for three pupil size ranges: ≤2.5 mm; >2.5 mm and <4.0 mm; and ≥4.0 mm.
Figure 1 presents the defocus curves for all three lens groups combined; results were adjusted for cases with residual refractive error following manifest refraction. Prominent near peaks are shown in Figure 1 at approximately -2.0 D for the ZKB00 (+2.75) IOL and -2.5 D for the ZLB00 (+3.25) IOL. Both ZKB00 (+2.75) and ZLB00 (+3.25) multifocal subjects were found to have a statistically significantly increased (p<0.0001) range of defocus with visual acuity of 20/40 or better compared to monofocal subjects (Figure 1 and Table 35), achieving the secondary study endpoint of increased range of defocus with visual acuity of 20/40 or better compared to the monofocal control group. For the ITT population, results were also statistically significant (p<0.0001) with similar improvements in favor of the TECNIS® Multifocal IOLs, Models ZKB00 and ZLB00.
**Figure 1:**
**Binocular Defocus Curves at 6 Months**
**Bilateral Subjects- ZKB00, ZLB00, and ZCB00**
**Substudy Safety Population**
PMA P980040/S049: FDA Summary of Safety and Effectiveness Data
Page 37
{37}
Table 35:
Mean of Diopter Range With Binocular Visual Acuity of 20/40 or Better at 6 Months
Defocus Testingᵃ Using Range of 0 to -4 Diopters
Substudy Safety Population
| IOL | N | Mean (D) | Std Dev. | P-valueᵇ |
| --- | --- | --- | --- | --- |
| ZKB00 (+2.75) | 59 | 3.16 | 0.50 | |
| ZCB00 | 61 | 1.75 | 0.70 | |
| Difference | | 1.42 | | <0.0001 |
| ZLB00 (+3.25) | 63 | 3.30 | 0.69 | |
| ZCB00 | 61 | 1.75 | 0.70 | |
| Difference | | 1.56 | | <0.0001 |
ᵃ Adjusted for cases with residual refractive error following manifest refraction
ᵇ P-value is from one-sided two-sample t-test
The defocus results of the ZKB00 (+2.75) and ZLB00 (+3.25) multifocal IOLs strongly illustrate the multifocality of the optic design at any pupil size for both the ZKB00 IOL (Figure 2) and the ZLB00 IOL (Figure 3). Minimal pupil size effect was observed.
Figure 2:
Binocular Defocus Curve by Average Pupil Size at 6 Months
Bilateral Subjects—ZKB00
PMA P980040/S049: FDA Summary of Safety and Effectiveness Data
Page 38
{38}
**Binocular Defocus Curve by Average Pupil Size at 6 Months**
### Spectacle Independence
The Modified TyPE Specification for Cataracts (Jonathan Javitt, M.D., M.P.H.) questionnaire was used to collect information on spectacle usage, visual quality, optical/visual symptoms and other items. The study questionnaires were administered by telephone by third-party, trained interviewers following the completion of the 6-month study exams. Interviewers were masked regarding subject lens type (multifocal or monofocal). The spectacle independence study endpoint was based on a single question from the questionnaire: “How often do you wear glasses?” with the response options of “always,” “sometimes” or “never;” only the response “never” was considered spectacle independent. This item was not determined to be a psychometrically valid assessment of the concept of spectacle independence. Both TECNIS® Multifocal IOLs, Models ZKB00 and ZLB00, achieved the secondary endpoint of the overall rates of “never using spectacles” for the ZKB00 (+2.75) and ZLB00 (+3.25) lens groups were statistically significa…
