SBL-3 Multifocal Intraocular Lens

P200020 · Lenstec, Inc. · MFK · Jul 22, 2022 · Ophthalmic

Device Facts

• Record ID: P200020
• Device Name: SBL-3 Multifocal Intraocular Lens
• Applicant: Lenstec, Inc.
• Product Code: MFK · Ophthalmic
• Decision Date: Jul 22, 2022
• Decision: APPR
• Regulation: 21 CFR 886.3600
• Device Class: Class 3
• Attributes: Therapeutic

Intended Use

The SBL-3™ multifocal intraocular lens is indicated for primary implantation for the visual correction of aphakia, in adult patients with 1 diopter or less of pre-existing corneal astigmatism, in whom a cataractous lens has been removed. The lens mitigates the effects of presbyopia by providing a bifocal correction. Compared to an aspheric monofocal IOL, the lens provides improved near visual acuity, while maintaining comparable distance and intermediate visual acuity. The lens promotes the less frequent use of vision correction choices at near distance (including glasses, contact lenses, magnifying glasses, and digital adjustments on electronic devices), compared to an aspheric monofocal IOL. The SBL-3™ multifocal IOL is intended for capsular bag placement only.

Device Story

SBL-3™ is a single-piece, ultraviolet-absorbing, hydrophilic acrylic multifocal intraocular lens (MIOL) for capsular bag placement after phacoemulsification. It features a rotationally asymmetric, aspheric, segmented optic with two distinct power zones: superior for distance and inferior for near (+3.00D add at IOL plane). Unlike concentric zonal MIOLs, this design provides bifocal correction without requiring head movement. Used by ophthalmic surgeons in clinical settings to replace the human crystalline lens; the patient's brain adapts to the bifocal images. The device mitigates presbyopia, improving near visual acuity and reducing dependence on reading glasses or digital magnifiers while maintaining distance/intermediate vision. Potential benefits include spectacle independence at near distances; risks include visual disturbances (halos, glare, starbursts) and potential for secondary surgical intervention.

Clinical Evidence

Prospective, multi-center, randomized, subject-masked pivotal study (IDE G140134) with 499 subjects (333 test, 166 control). Primary endpoints: monocular DCNVA at 40cm (superiority), DCIVA at 70cm (non-inferiority), and BCDVA at 4m (non-inferiority) at 1-year. Results: SBL-3 superior for near acuity (0.109 vs 0.569 LogMAR, p<0.0001). Non-inferior for intermediate and distance acuity. Safety: SSI rate 1.8% (12/656), higher than historical control. Increased visual disturbances (halos, glare) reported. No significant difference in contrast sensitivity compared to other marketed MIOLs.

Technological Characteristics

Material: Hydrophilic acrylic (26% water content) with UV blocker. Design: Single-piece, closed-loop/modified plate haptics, 5.75mm optic, 11.00mm length. Refractive, equiconvex, aspheric, rotationally asymmetric segmented optic. Sterilization: Steam. Connectivity: None. Software: None.

Indications for Use

Indicated for primary implantation for visual correction of aphakia in adult patients (≥22 years) with ≤1 diopter of pre-existing corneal astigmatism following cataract removal. Contraindicated in patients with uncontrolled glaucoma, microphthalmia, chronic severe uveitis, retinal detachment, corneal decompensation, diabetic retinopathy, iris atrophy, or perioperative complications.

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.

Reference Devices

• Softec HD Posterior Chamber Intraocular Lens (P090022)
• Akreos AO60 (Bausch + Lomb)

Submission Summary (Full Text)

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SUMMARY OF SAFETY AND EFFECTIVENESS DATA (SSED)

I. GENERAL INFORMATION

Device Generic Name: Multifocal intraocular lens
Device Trade Name: SBL-3™ Multifocal Intraocular Lens
Device Procode: Multifocal intraocular lens (MFK)
Applicant’s Name and Address: Lenstec Inc
1765 Commerce Avenue North,
St. Petersburg, FL 33716
Date(s) of Panel Recommendation: None
Premarket Approval Application (PMA) Number: P200020
Date of FDA Notice of Approval: July 22, 2022

II. INDICATIONS FOR USE

The SBL-3™ multifocal intraocular lens is indicated for primary implantation for the visual correction of aphakia, in adult patients with 1 diopter or less of pre-existing corneal astigmatism, in whom a cataractous lens has been removed. The lens mitigates the effects of presbyopia by providing a bifocal correction. Compared to an aspheric monofocal IOL, the lens provides improved near visual acuity, while maintaining comparable distance and intermediate visual acuity. The lens promotes the less frequent use of vision correction choices at near distance (including glasses, contact lenses, magnifying glasses, and digital adjustments on electronic devices), compared to an aspheric monofocal IOL. The SBL-3™ multifocal IOL is intended for capsular bag placement only.

III. CONTRAINDICATIONS

Outside of general contraindications for ocular surgery, the following specific contraindications apply:

Uncontrolled glaucoma, microphthalmia, chronic severe uveitis, retinal detachment, corneal decompensation, diabetic retinopathy, iris atrophy, perioperative complications, potentially foreseeable post-operative complications and other conditions which an ophthalmic surgeon might identify based on their experience.

IV. WARNINGS AND PRECAUTIONS

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The warnings and precautions can be found in the SBL-3 labeling.

## V. DEVICE DESCRIPTION

The SBL-3™ Multifocal Intraocular Lens (MIOL) is an ultraviolet absorbing, single-piece closed loop/modified plate intraocular lens intended for the replacement of the human crystalline lens following phacoemulsification cataract removal. The SBL-3 possesses a rotationally asymmetric aspheric multifocal optic with a +3.00 add on the anterior surface. It is offered in the dioptric power range of +15.0 to +25.0 in quarter (0.25) diopter increments and 25.5 to 30.0 in half (0.50) diopter increments. The SBL-3™ is manufactured with a tolerance ±0.11 diopters at both the base power and the add power, between +15.0 and +25.0. The lens features, specifications, power offerings and tolerances are described in Tables 1 and 2.

Table 1: SBL-3™ Specifications

| Lens Feature | Specifications |
| --- | --- |
| Optic Size | 5.75 mm |
| Optic Type | Refractive, equiconvex, aspheric |
| Haptic Type | Closed loop/modified plate |
| Add power | +3.00D at the IOL plane
+2.40D at the spectacle plane |
| Length | 11.00 mm |
| Angulation | 0 Degrees |
| Construction | 1 Piece |
| Optic Material | Hydrophilic acrylic (26% water content) |
| Haptic Material | Hydrophilic acrylic (same as optic) |
| Index of refraction | 1.456 |
| A Constant* | 118.00 mm* |
| A/C Depth* | 5.10 mm* |

*NOTE: The 'A' Constant and ACD values printed on the outside of the package, are estimates only. It is recommended that the surgeon determine his/her own values based on individual clinical experience

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Table 2: SBL-3™ Power Offering and Tolerances

| SBL-3 Power Ranges (D) | Diopter Increments Offered In (D) | Tolerances Applied (D)** |
| --- | --- | --- |
| +15.0 to +25.0 | 0.25 | ± 0.11 |
| +25.5 D to +30.0 | 0.50 | ± 0.25 |

The SBL-3™ is designed with a segmented optic, rather than the concentric zonal approach used in currently available MIOLs (Figure 1). The optic is designed with two distinct power zones, with the superior aspect powered for distance and the inferior powered for near. The ‘near’ zone possesses 3.0 diopters (D) of additional (ADD) power at the IOL plane, which corresponds to approximately 2.4D at the spectacle plane, depending on corneal power and anterior chamber depth. The add portion is placed on the anterior MIOL surface.

Figure 1: SBL-3™ Multifocal Intraocular Lens

The SBL-3™ is manufactured from a medical grade co-polymer of Hydrophilic Acrylic, with a polymerizable UV blocker. The hydrophilic nature of the lens material (hydrophilic acrylic) reduces the problems associated with silicone oil adhesion and silicone oil induced opacification. Each MIOL has a 360° square edge design.

The IOL is designed with a half power ring at the very bottom of the optic portion. This is depicted in the Figure 2 below, in which the green color represents the distance portion, the red portion represents the near add portion and the adjacent white colored portion represents this half power portion. In eyes with large pupils, it is possible that patients may see a resultant arcuate half-halo. No patient in the clinical trial noted such a concern, but the theoretical possibility exists that such an issue could occur.

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Figure 2: SBL-3™ IOL Optic

Currently available MIOLs are designed in a concentric ring fashion in which powers change from the base power to the near power in alternating fashion, from one central ring all the way to the periphery of the optic. The number of rings varies by manufacturer/lens/design.

Although the design appears similar to bifocal spectacles in concept, the patient implanted with the SBL-3™ does not need to move his/her head up and down to gain the advantage of the near add (as is required with bifocal spectacles). Just as with approved two-power MIOLs in the US, the patient's brain adapts to the available images and suppresses the out of focus image associated with those objects not being focused on by the patient.

The SBL-3™ is manufactured from the same material approved for use with the Applicant's Softec family of IOLs (P090022). The SBL-3™ is lathe and mill cut from a 'button' of material and subsequently hydrated, polished, checked for acceptability, final cleaned/inspected, packaged in a pouch, labeled, sterilized, packed and then shipped.

Table 3, below, describes the injection systems which are approved for use with the SBL-3.
Table 3: IOL Injection System Compatibility Guide

| | IOL Injection Systems | | | |
| --- | --- | --- | --- | --- |
| IOL Model | LC Injection System (K122848) (Lenstec Inc) | | Softip Injection System (K103495) (Asico LLC) | |
| | Validated for Use | Power range (D) | Validated for Use | Power range (D) |
| SBL-3 | ✓ | I-9011S/ LC16: 15.0 to 22.0 | ✓ | AS-9300/ LC1620I: 15.0 to 22.0 |
| | ✓ | I-9011S/ LC1620: 15.0 to 22.0 | ✓ | AS-9310/ LC2420I: 15.0 to 30.0 |
| | ✓ | I-9011S/ LC2420: 15.0 to 30.0 | | |
| | ✓ | I-9012/ LC16: 10.0 to 26.0 | | |

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VI. ALTERNATIVE PRACTICES AND PROCEDURES

There are several other alternatives for the correction of of aphakia resulting from surgical cataract removal (i.e., for patients who have had a cataractous lens removed). Non-surgical options include special cataract glasses or contact lenses. Surgical options such as monofocal, multifocal, extended depth of focus or accommodative IOLs are also available. 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 SBL-3™ has been marketed in the following countries: Argentina, Barbados/Caribbean, Belgium, Canada, China/Hong Kong, Colombia, Czech Republic/Slovakia, Georgia, Germany, Iraq, Ireland, New Zealand, Panama, South Korea, Switzerland, Taiwan, United Kingdom, and Zimbabwe. The SBL-3™ has never been withdrawn from marketing for any reason related to its safety or effectiveness.

VIII. POTENTIAL ADVERSE EFFECTS OF THE DEVICE ON HEALTH

Below is a list of the potential adverse effects (e.g., complications) associated with the use of the device.

- lens epithelial cell down-growth
- corneal endothelial damage
- infection (endophthalmitis)
- retinal detachment/tear
- vitritis
- cystoid macular edema
- corneal edema
- pupillary block
- cyclitic membrane
- iris prolapse
- hypopyon
- anterior uveitis
- hyphema
- pigment dispersion
- posterior capsule opacification
- transient or persistent glaucoma
- IOL dislocation, tilt, or decentration requiring repositioning
- residual refractive error resulting in secondary intervention

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- increased visual symptoms (compared to a monofocal IOL) related to the optical characteristics of the IOL, including bothersome stray-light artifacts such as halo, starbursts, or glare

Secondary surgical interventions include, but are not limited to: lens repositioning, lens replacement, vitreous aspiration, iridotomy for pupillary block, wound leak repair, and retinal detachment repair.

For the specific adverse events that occurred in the clinical study, please see Section X below.

## IX. SUMMARY OF NONCLINICAL STUDIES

The SBL-3™ is made of the same material as the approved Softec HD Posterior Chamber Intraocular Lens IOL (P090022). Therefore, please refer to P090022, which is incorporated by reference into this PMA.

### A. Laboratory Studies

#### Physicochemical testing

The SBL-3™ is manufactured from the identical Hydroxyethylmethacrylate (HEMA) material as the Softec HD monofocal IOL (P090022). The materials used for the SBL-3™ has been previously tested to meet the recommendations in 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.

### B. Animal Studies

#### Biological Testing

The animal studies were conducted using the Softec HD Posterior Chamber Intraocular Lens (P090022). The materials used for the SBL-3™ were identified as the same as what was evaluated in P090022 and leveraged. Biocompatibility testing (see Table 4) was performed in accordance with International Standard Organization (ISO) 10993-1 - Biological evaluation of medical devices - Part 1: Evaluation and testing within a risk management process, - Part 3: Tests for genotoxicity, carcinogenicity and reproductive toxicity, - Part 5: Tests for in vitro cytotoxicity, - Part 6: Tests for local effects after implantation, - Part 10: Tests for irritation and skin sensitization, and - Part 11: Tests for systemic toxicity. All biocompatibility testing were conducted in accordance with the provisions of 21 CFR 58, Good Laboratory Practice for Nonclinical Laboratory Studies. The toxicology studies were conducted in accordance with the requirements of International Standard Organization (ISO) 11979-5, Ophthalmic implants – Intraocular lenses – Part

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5: Biocompatibility. All acceptance criteria for biocompatibility were met.

Table 4: Biocompatibility Testing

| Test | Purpose | Acceptance Criteria | Results |
| --- | --- | --- | --- |
| MEM Elution with L-929 Mouse Fibroblast Cells | Evaluate the potential for cellular toxicity | Non-cytotoxic | Negative for cytotoxicity |
| Agarose Overlay (Direct Contact) with L-929 Mouse Fibroblast (solid) | Evaluate the potential for cellular toxicity | Non-cytotoxic | Negative for cytotoxicity |
| Agarose Overlay (Direct Contact) with L-929 Mouse Fibroblast (liquid) | Evaluate the potential for cellular toxicity | Non-cytotoxic | Negative for cytotoxicity |
| Cell Growth Inhibition Assay with L-929 Mouse Fibroblast Cells | Evaluate the potential for cellular toxicity | Non-cytotoxic | Negative for cytotoxicity |
| Guinea Pig Maximization Sensitization | Evaluate the potential of sensitization | Non-sensitizing | Negative for contact sensitization |
| Rabbit Muscle Implantation/Intracutaneous Study (2, 4 week implant) | Evaluate the local effects in skeletal muscle tissue | Non-irritant | No significant biological local response |
| Acute Systemic Toxicity | Evaluate toxicity in muscle tissue | Non-toxic | No significant biological response |
| Bacterial Reverse Mutation Mutagenicity Test (DMSO, saline extract) | Evaluate the mutagenic potential | Non-mutagenic | Negative mutagenic potential |
| Chromosomal Aberration Study | Evaluate the genotoxicity potential | Non-genotoxic | Negative genotoxic potential |
| Mouse Peripheral Blood Micronucleus Study | Evaluate potential to cause gene mutations | Non-mutagenic | Negative mutagenic potential |
| Hemolysis Study | Evaluate potential to cause hemolysis | Non-hemolytic | Neagtive for hemolysis |

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## C. Additional Studies

### Optical/Mechanical Testing

The Table 5 below provides results of optical and mechanical testing following aging. The acceptance criteria are either the LensTec specifications, the specifications in the ISO 11979 series of IOL standards, or a determination that there was no significant change from the baseline values, as applicable. All acceptance criteria for optical and mechanical attributes were met after aging. The preclinical optical and mechanical testing were performed with the SBL-3 and measured in accordance with ISO 11979-2 Ophthalmic Implants – Intraocular Lenses – Part 2: Optical Properties and Test Methods and ISO 11979-3 Ophthalmic Implants – Intraocular Lenses – Part 3: Mechanical Properties and Test Methods.

Table 5: Optical and Mechanical Testing following Real/Accelerated Aging

| Test | Purpose | Acceptance Criteria | Results |
| --- | --- | --- | --- |
| Tolerances and Dimensions | To characterize the tolerance of the IOL | N/A | Characterized |
| Compression Force | To characterize the force to compression the IOL | N/A | Characterized |
| Axial Displacement in Compression | To characterize the axial displacement in compression | N/A | Pass |
| Optic Decentration | To assess optic decentration under compression | Mean and 2 SD not greater than 10% of clear optic | Pass |
| Optic Tilt | To assess optic tilt under compression | Mean and 2 SD not greater than 5 degrees | Pass |

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| Angle of Contact | To characterize haptic contact with ocular tissues | N/A | Characterized |
| --- | --- | --- | --- |
| Compression Force Decay | To characterize the force to compress the IOL after 24 hours decay | N/A | Characterized |
| Dynamic Fatigue Durability | To assess the ability of the haptics to withstand cyclic compressive loading | No haptic breakage | Pass |
| Surgical Manipulation/Haptic Strength | To assess the force to separate the haptic from the optic | Greater than or equal to 0.25 N | Pass |
| Surface and Bulk Homogeneity | To assess conformance to dimensional tolerances and free of surface defects | Multiple acceptance criteria described in ISO 11979-3 | Pass |
| Spectral Transmittance | To characterize the spectral transmittance of the IOL | Multiple acceptance criteria described in ISO 11979-2 | Characterized |
| Dioptric Power1 | To assess accuracy of optical power, meet minimum image quality specifications | Acceptance criteria described in ISO 11979-2 | Pass |
| Image Quality | To assess image quality of the IOL by modulation transfer function (MTF) | Multiple acceptance criteria described in ISO 11979-2 | Pass |
| Optical Evaluation After | To assess the ability of the IOL to | Multiple acceptance | Pass |

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The MTF through focus response at 50 lp/mm for a 2.0, 3.0, and 4.5 mm aperture is shown in Figure 3.

Figure 3: Through-focus MTF Values at 50 cyc/mm
Figure 4 describes the SBL-3 spectral transmittance over the $300\mathrm{nm}$ to $1100\mathrm{nm}$ wavelengths. The $\%$ UV transmittance from $300 - 360\mathrm{nm}$ is $0\%$ and the $10\%$ cut off is $374\mathrm{nm}$ .

Figure 4: Spectral transmittance

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# Microbiology, Sterilization, and Shelf-Life Testing

The IOL material, sterilization method, packaging materials and packaging configuration of the SBL-3™ Multifocal IOLs are the same as those of Lenstec's approved Softec HD Posterior Chamber Intraocular Lens (P090022). Differences in the manufacturing process, including initial manufacturing location, manufacturing methods and manufacturing equipment have been evaluated and are considered acceptable with respect to microbiology, sterilization and shelf life/transport stability. As a result, stability, packaging integrity, and transport stability data supporting this reference Softec HD monofocal IOL lens model was used to support the application for the SBL-3™ multifocal IOL lens model. In addition, both accelerated aging and real-time aging studies were performed. As a result of reference and current stability testing, the SBL-3™ IOLs will be labeled with a 5-year shelf life.

Validation of the steam sterilization process was conducted on the SBL-3™ IOLs and assures a minimum sterility assurance level of $10^{-6}$. The SBL-3™ IOLs were successfully adopted into the existing validated steam sterilization cycle per the appropriate standard operating procedures and passed all acceptance criteria for bioburden and bacterial endotoxin.

These tests were conducted in accordance with the current versions of the following standards:

- ISO 17665-1, Sterilization of health care products – Moist Heat – Part 1:
- Requirements for the development, validation, and routine control of a sterilization process for medical devices
- ISO 17665-2, Sterilization of health care products – Moist Heat – Part 2: Guidance on the application of ISO 17665-1
- ISO 11737-1, Sterilization of health care products—Microbiological methods—Part 1: Determination of a population of microorganisms on products

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- ISO 11979-6, Ophthalmic Implants – Intraocular Lenses – Part 6: Shelf-life and transport stability
- ISO 11979-8, Ophthalmic Implants – Intraocular Lenses – Part 8: Fundamental requirements
USP $&lt; 85&gt;$ , Bacterial Endotoxins Test
- ASTM F88-15, Standard Test Method for Seal Strength of Flexible Barrier Materials
- ASTM D3078-02(2013), Standard Test Method for Determination of Leaks in Flexible Packaging by Bubble Emission
- ASTM F1929-15, Standard Test Method for Detecting Seal Leaks in Porous Medical Packaging by Dye Penetration

The results of the sterilization, packaging, shelf life and transport stability studies are summarized in Table 6 below:

Table 6: Microbiology, Sterilization, and Shelf-Life Testing: SBL-3™ Multifocal IOL

| Test | Purpose | Acceptance Criteria | Results |
| --- | --- | --- | --- |
| Pre-sterilization Bioburden Testing | Determine natural bioburden prior to sterilization to ensure a sterility assurance level (SAL) of 10-6can be met per ANSI/AAMI/ISO 11737-1: 2018 Section 6 | Achieve SAL of 10-6 | Pass |
| Steam sterilization requalification | Validates that the steam sterilization cycle is effective per EN ISO 17665-1: 2006/(R)2013 Section 12 | Achieve SAL of 10-6 | Pass |
| Bacterial Endotoxin Testing | Confirm product is non-pyrogenic per USP <85> | ≤0.12 EU/ml | Pass |
| Package Integrity Testing – Legibility of Labeling | Confirm that product labeling remains legible after sterilization during stability studies per ISO 11979-6 Section 4.3 | Label remains legible | Pass |
| Packaging Integrity Testing – Seal Strength | Confirm that product seal strength is maintained after sterilization during stability studies per ISO | Minimum seal strength is 1 lb/in | Pass |

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| | 11979-6 Section 4.3 and ASTM F88-15 | | |
| --- | --- | --- | --- |
| Packaging Integrity Testing – Bubble Emission | Confirm that product seal integrity is maintained after sterilization during stability studies per ISO 11979-6 Section 4.3 and ASTM D3078-02(2013) | Fluid in package after 30 seconds of submission | Pass |
| Packaging Integrity Testing – Dye Penetration | Confirm that product seal integrity is maintained after sterilization during stability studies per ISO 11979-6 Section 4.3 and ASTM F1929-15 | No leaks detected at four (4) distinct seal edge points | Pass |

X. SUMMARY OF PRIMARY CLINICAL STUDY(IES)

The applicant performed a clinical study to establish a reasonable assurance of safety and effectiveness of cataract surgery and intraocular lens (IOL) implantation with the SBL-3™ ultifocal IOL for primary implantation for the visual correction of aphakia in the US under IDE G140134. 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

Patients were treated between August 19, 2015 and August 15, 2019. The database for this Original PMA Application reflected data collected through August of 2019 and included 495 implanted subjects. There were 18 investigational sites in the U.S. The study was enrolled in two phases (Phase 2 and Phase 3).

The study was a prospective, multi-center, pivotal, two-arm/parallel group, subject masked, randomized (2:1 ratio) cohort study. Subjects were masked from knowing the type of IOL they received, either multifocal SBL-3™ or monofocal IOL control. The study was intended to include pre-operative visits and extend to 1-year post-operative. The subjects were enrolled following signing informed consent and meeting inclusion and exclusion criteria and randomized at the time of surgery into either the test or control group. Once the primary eye was treated, the fellow eye was to be implanted with the same type IOL between 7 and 30 days from the primary eye implantation date. Both eyes were required to meet inclusion/exclusion

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criteria for this reason. The statistical plan was based upon the use of frequentist statistics. Sample size was based upon adequate power to test key effectiveness hypotheses comparing the SBL-3™ arm to the monofocal control arm, with regard to distance-corrected visual acuity at 4 m and 70 cm (to show non-inferiority, using a 0.10 logMAR margin), and at 40 cm (to show superiority).

The safety objective was to characterize the rates of all adverse events in the SBL-3™ arm and to statistically compare these to rates seen in with a monofocal IOL. For types of adverse events listed in the ISO 11979-7 (2018) (Ophthalmic implants - Intraocular lenses - Part 7: Clinical investigations), SBL-3™ adverse event rates were compared to the ISO historical control rates found in monofocal IOLs. Statistically, SBL-3™ rates were compared to the historical control rates to determine whether the observed rates were significantly greater than the historical control rates. Secondary surgical intervention due to the optical properties of the IOL (which is not a type of event mentioned in this ISO historical control) was part of the primary safety endpoint. The analysis was to compare the rates in the SBL-3 and active monofocal IOL control arms using a 2-sided 90% confidence interval constructed around the estimate of the rate difference between the arms. (The group rates wound be considered comparable if the confidence interval contains zero. Similar statistical comparisons were the analyses used for any types of serious adverse events not found in the historical control.)

The control group was the subjects implanted with a legally marketed aspheric monofocal IOL with indications for primary implantation for the visual correction of aphakia (the Akreos AO60 (Bausch + Lomb, NJ, USA)). (For the types of safety and performance endpoints (SPEs) specified in ISO 11979-7, the ISO historical control was used for statistical comparisons.)

A total of up to 510 subjects were allowed to be enrolled, in order to ultimately have 300 study subjects and 150 control subjects available at the 1-year postoperative. Enrollment was closed after the 499th subject was included in the study.

1. Clinical Inclusion and Exclusion Criteria

Enrollment in the IDE study for the SBL-3™ was limited to patients who met the following inclusion criteria:

- ≥ 22 years of age, of any race and either gender
- Operable, age related cataract grade in both eyes
- Patients who require an IOL power in the range of 15 D – 30 D only.
- Able to comprehend and sign a statement of informed consent
- Planned cataract removal by phacoemulsification

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- Potential postoperative visual acuity of 0.2 logMAR or better in both eyes
- In good general and ocular health
- Patients with preoperative astigmatism ≤1.0 D
- Note: Corneal incisions made to reduce astigmatism will not be allowed during the course of the study.
- Clear intraocular media other than cataract in study eyes
- Preoperative Best Corrected Distance Visual Acuity worse than 0.20 logMAR with or without medium BAT (Brightness Acuity Test)
- The subject must be able to undergo second eye surgery between 7 days and 30 days of the first eye surgery
- Able to competently complete testing
- Willing and able to attend study visits

Patients were not permitted to enroll in the IDE study for the SBL-3™ if they met any of the following exclusion criteria:

- Previous intraocular surgery
- Preoperative photopic pupil size of &lt; 2.75 mm
- Previous corneal refractive surgery
- Any inflammation or edema (swelling) of the cornea
- Pterygium with corneal involvement or has the potential of corneal involvement (in the opinion of the Investigator) during the course of the study
- Subjects with diagnosed degenerative visual disorders (e.g. macular degeneration or other retinal disorders) that are predicted to cause future acuity losses to a level worse than 0.2 LogMAR
- Subjects who may reasonably be expected to require a secondary surgical intervention at any time during the study (other than YAG capsulotomy)
- Amblyopia
- Clinically significant ptosis
- Clinically severe corneal dystrophy (e.g., epithelial, stromal, or endothelial dystrophy), keratitis, keratoconjunctivitis, keratouveitis, keratopathy, or kerectasia
- Diabetic Retinopathy
- Extremely shallow anterior chamber, not due to swollen cataract
- Microphthalmia
- Previous retinal detachment
- Previous corneal transplant
- Severe dry eye
- Recurrent severe anterior or posterior segment inflammation of unknown etiology
- Systemic medications that may confound the outcome or increase the risk to the subject in the opinion of the Investigator [tamsulosin

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hydrochloride (Flomax) or other medications with similar side effects (floppy iris syndrome)]

- Rubella or traumatic cataract
- Iris neovascularization
- Glaucoma (medically controlled or uncontrolled)
- Aniridia
- Chronic severe uveitis
- Optic nerve atrophy
- Corneal decompensation
- Greater than 1.0 D of astigmatism
- History of corneal disease (e.g., herpes simplex, herpes zoster keratitis, etc.)
- Pseudoexfoliation syndrome
- Iris atrophy
- Pupil abnormalities (e.g., corectopia)
- Aniseikonia
- An acute or chronic disease or illness that may confound the results of this investigation (e.g., immunocompromised, connective tissue disease, clinically significant atopic disease, diabetes, and any other such disease or illness)
- Pregnant, lactating, or planning to become pregnant during the course of the trial
- Note: Subjects who become pregnant during the study will not be discontinued; however, data may be excluded from the effectiveness analyses because pregnancy can alter refraction and visual acuity results. Participation in another clinical trial within 30 days of study start
- Participation in another clinical trial within 30 days of study start

The following were criteria for not implanting the study device (after enrollment and during surgical visit)

- Other planned ocular surgery procedures, including but not limited to, LASIK, astigmatic keratotomy and limbal relaxing incisions for the duration of the study
- Significant vitreous loss
- Mechanical or surgical manipulation required to enlarge the pupil; pupil size must be at least 4.5 mm or larger just prior to implantation
- Excessive iris mobility
- Capsular rent or tear
- Significant anterior chamber hyphema
- Uncontrollable intraocular pressure
- Iris damage
- Detached Descemet’s Membrane
- Zonular or capsular rupture

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- Bag-sulcus, sulcus-sulcus or unknown placement of the haptics

2. Follow-up Schedule

The visit schedule and clinical evaluations are presented in Table 7, below. All patients were scheduled to return for follow-up examinations as follows:

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Table 7: Schedule of Visits for Subjects in the SBL-3 IDE Study

| Activity | Visit 0/0A | Visit 00 | Visit 1* | Visit 2* | Visit 3* | Visit 00A* | Visit 1A* | Visit 2A* | Visit 3A* | Visit 4A* | Visit 5A* |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
| | Preop | Op | 1-2 Days Postop | 7-14 Days Postop | 30-60 Days Postop | \(Op^a\) | 1-2 Days Postop | 7-14 Days Postop | 30-60 Days Postop | 120-180 Days Postop | 330-420 Days Postop |
| Informed Consent | X | | | | | | | | | | |
| Demographics | X | | | | | | | | | | |
| General Information / Medical History | X | | | | | | | | | | |
| Manifest Refraction | X | | X | X | X | | X | X | X | X | X |
| Inclusion/Exclusion Criteria | X | \(X^b\) | | | | \(X^b\) | | | | | |
| Urine Pregnancy Test | X | | | | | | | | | | |
| Device Deficiencies | | X | X | X | X | X | X | X | X | X | X |
| Adverse Events | X | X | X | X | X | X | X | X | X | X | X |
| Light Measurements | X | | X | X | X | | X | X | X | X | X |
| Photopic Pupil Size at Near, Intermediate and Distance | X | | | | | | | | | X | X |

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| Activity | Visit 0/0A | Visit 00 | Visit 1* | Visit 2* | Visit 3* | Visit 00A* | Visit 1A* | Visit 2A* | Visit 3A* | Visit 4A* | Visit 5A* |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
| | Preop | Op | 1-2 Days Postop | 7-14 Days Postop | 30-60 Days Postop | Op* | 1-2 Days Postop | 7-14 Days Postop | 30-60 Days Postop | 120-180 Days Postop | 330-420 Days Postop |
| Distance Visual Acuity | | | | | | | | | | | |
| Mesopic Pupil Size at Near, Intermediate and Distance | X | | | | | | | | | X | X |
| Uncorrected Distance Visual Acuity | X | | X | X | X | | X | X | X^{c} | X^{c} | X^{c} |
| Best Corrected Distance Visual Acuity Using Original Manifest Refraction | X | | X | X | X | | X | X | X^{c} | X^{c} | X^{c} |
| Best Corrected Distance Visual Acuity Using Additional -0.25 D | X | | X | X | X | | X | X | X^{c} | X^{c} | X^{c} |
| Mesopic Low Contrast Acuity Testing | | | | | | | | | | X^{f} | |
| Near Visual Acuity at 40 cm | | | | | | | | | | | |
| Uncorrected Near Vision at 40 cm | | | X | X | X | | X | X | X^{c} | X^{c} | X^{c} |

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| Activity | Visit 0/0A | Visit 00 | Visit 1* | Visit 2* | Visit 3* | Visit 00A* | Visit 1A* | Visit 2A* | Visit 3A* | Visit 4A* | Visit 5A* |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
| | Preop | Op | 1-2 Days Postop | 7-14 Days Postop | 30-60 Days Postop | Opa | 1-2 Days Postop | 7-14 Days Postop | 30-60 Days Postop | 120-180 Days Postop | 330-420 Days Postop |
| Distance Corrected Near Vision at 40 cm | | | | | X | | | | Xc | Xc | Xc |
| Mesopic Distance Corrected Near Vision at 40 cm | | | | | | | | | | Xc | Xc |
| Best Corrected Near Vision at 40 cm | | | | | X | | | | Xc | Xc | Xc |
| Near Visual Acuity at Best Distance | | | | | | | | | | | |
| Uncorrected Near Visual Acuity at Best Distance | | | | | X | | | | Xc | Xc | Xc |
| Distance Corrected Near Visual Acuity at Best Distance | | | | | X | | | | Xc | Xc | Xc |
| Intermediate Visual Acuity at 70 cm | | | | | | | | | | | |
| Uncorrected Intermediate Visual Acuity at 70 cm | | | | | X | | | | Xc | Xc | Xc |

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| Activity | Visit 0/0A | Visit 00 | Visit 1* | Visit 2* | Visit 3* | Visit 00A* | Visit 1A* | Visit 2A* | Visit 3A* | Visit 4A* | Visit 5A* |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
| | Preop | Op | 1-2 Days Postop | 7-14 Days Postop | 30-60 Days Postop | Opa | 1-2 Days Postop | 7-14 Days Postop | 30-60 Days Postop | 120-180 Days Postop | 330-420 Days Postop |
| Distance Corrected Intermediate Visual Acuity at 70 cm | | | | | | X | | | X^{c} | X^{c} | X^{c} |
| Corneal Topography | X | | | | | | | | | | |
| Target Residual Refractive Error | X | | | | | | | | | | |
| Contrast Sensitivity Photopic (with and without glare) | | | | | | | | | | X^{d} | X^{d} |
| Contrast Sensitivity Mesopic (with and without glare) | | | | | | | | | | X^{d} | X^{d} |
| Binocular Defocus | | | | | | | | | | X^{d} | |
| Anterior Chamber Depth | X | | | | | | | | | | |
| Axial Length | X | | | | | | | | | | |
| Keratometry | X | | | | | | | | | X | |
| Intraocular Pressure | X | | | X | X | X | X | X | X | X | X |
| PRO Questionnaire s | X | | X^{g} | | | | | | X^{e} | X | X |
| Concomitant Medications | X | | X | X | X | X | X | X | X | X | X |
| Activity | Visit 0/0A | Visit 00 | Visit 1* | Visit 2* | Visit 3* | Visit 00A* | Visit 1A* | Visit 2A* | Visit 3A* | Visit 4A* | Visit 5A* |
| | Preop | Op | 1-2 Days Postop | 7-14 Days Postop | 30-60 Days Postop | Opa | 1-2 Days Postop | 7-14 Days Postop | 30-60 Days Postop | 120-180 Days Postop | 330-420 Days Postop |
| Operative Eye | | | X | | | | X | | | | |
| Surgical Problems | | | X | | | | X | | | | |
| Other Procedures at surgery | | | X | | | | X | | | | |
| Folding and Insertion Instrument | | | X | | | | X | | | | |

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| Incision Site and Size | | X | | | | X | | | | | |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
| Haptic Placement | | X | | | | X | | | | | |
| Lens Information | | X | | | | X | | | | | |
| Slit Lamp Exam | X | | X | X | X | | X | X | X | X | X |
| Dilated Fundus Exam | X | | | | X | | | | X | X | X |
| Secondary Surgical Interventions | | | X | X | X | | X | X | X | X | X |
| IOL Observations | | | X | X | X | | X | X | X | X | X |
| IOL Position Change | | | X | X | X | | X | X | X | X | X |
| Posterior Capsulotomy | | | X | X | X | | X | X | X | X | X |
| Subjective Posterior Capsule Opacification | | | X | X | X | | X | X | X | X | X |
| Lens Orientation | | X | X | X | X | X | X | X | X | X | X |
| Functional Performance | | | | | | | | | | X^{d} | |

*: Visit and Testing performed on All Subjects
a. Second Implantation can be done within 7-30 days of first implantation
b. Review of Inclusion/Exclusion criteria prior to surgery
c. Monocular and Binocular testing
d. Binocular testing only
e. Administration of PRO twice at Form 3A (once at beginning of visit and once prior to dilation) for up to an additional 100 Phase 3 subjects only
f. Only administered if the subject has a ≥ 10 letter loss in visual acuity or is complaining of visual disturbances
g. PRO is administered prior to sedation and dilation for up to an additional 100 Phase 3 subjects only

## Subgroup populations:

There were two sub-studies involved in the IDE study associated with the SBL-3™. These were defocus evaluation and functional performance (driving simulator). These were both performed at the Form 4A (120-180 days post-operative) visit.

## 3. Clinical Endpoints

With regards to safety, the primary endpoint was the rates of observed adverse events of various types, including the rate of secondary surgical intervention (SSIs) due to the optical properties of the IOL. As mentioned above, the rate of SSIs due to optical properties of the IOL was to be considered acceptable if it was not statistically, significantly higher than the rate for the active monofocal control. For types of serious adverse events listed (among the “safety and performance endpoints) in the ISO 11979-7(2018), the outcome for each type of adverse event was considered successful if the SBL-3™ rate was not statistically significantly higher than the historical control rate.

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There was one secondary safety endpoint: binocular distance contrast sensitivity, and 'other' safety endpoints, as listed below, and as noted in the statistical analysis plan (SAP).

- PRO Visual Disturbance Questionnaire (to include patient visual symptoms)
- Slit Lamp Examination
- Dilated Fundus Examination (to include adequacy of fundus visualization and clarity of retinal image)
- Subjective Posterior Capsule Opacification (PCO)
- Posterior Capsulotomy
- IOL Observations
- IOL Position Change (Tilt and Decentration)
- Intraocular Pressure
- Surgical Problems
- Device Deficiencies
- A loss of $\geq 10$ letters in Best Corrected Visual Acuity (LogMar) between any form evaluation and a later form evaluation
- Failure to achieve a Best Corrected LogMar acuity of 0.30 LogMAR (20/40) at any postoperative visit

The effectiveness objective was to compare the legally marketed monofocal to the study article and the ISO historical grid, for visual acuity outcomes.

a. There were three co-primary effectiveness endpoints at the 1-year postoperative visit:

- Photopic monocular Distance Corrected Near Visual Acuity at 40 cm at visit 5A (330-420 days). The hypothesis tested for the co-primary effectiveness endpoint #1 was to demonstrate superiority of the SBL-3™ IOL to the control monofocal IOL.
- Photopic monocular Distance Corrected Intermediate Visual Acuity at 70 cm at visit 5A (330-420 days). The hypothesis tested for the co-primary effectiveness endpoint #2 was to demonstrate non-inferiority of the SBL-3™ IOL to the control monofocal IOL (using a non-inferiority margin of 0.10 logMAR).
- Photopic monocular best corrected distance visual acuity at 4m at visit 5A (330-420 days). The hypothesis tested for the co-primary effectiveness endpoint #3 was to demonstrate non-inferiority of the SBL-3™ IOL to the control monofocal IOL (using a non-inferiority margin of 0.10 logMAR).

b. Secondary Endpoints

- The same three co-primary acuity endpoints/analyses, as above, but evaluated at visit 4A (120-180 days, postop)

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- Patient reported use (as reported on a patient questionnaire) of the frequency of use of vision correction (glasses/contact lenses) and spectacle independence at visit 5A (330-420 days)

There were other supportive effectiveness endpoints, including defocus curve characterization, and patient questionnaire assessment of patient satisfaction.

Note: The clinical protocol initially contained an error in the instructions for how to perform the testing for best corrected distance visual acuity (BCDVA). For discussion of this, see the portion of Section X under “Effectiveness Results” concerning the third co-primary effectiveness endpoint of BCDVA (see below, Table 38). (This discussion is also pertinent to the “other” safety endpoint of “Proportion of Eyes Achieving Best Corrected Distance Visual Acuity (BCDVA) of 0.30 LogMar (or better).”)

## B. Accountability of PMA Cohort

At the time of database lock, of 499 patients enrolled in the PMA study, 95.4% (476) patients are available for analysis at the completion of the study, the 12 month post-operative visit.

A total of 499 subjects were randomized into this study and randomized to receive either the test or control IOL. Of the 499 subjects randomized into the study, 333 were test subjects and 166 were control subjects. Of the 499 subjects randomized into the study, 495 had at least one operative eye implanted (329 in the SBL-3 group and 166 in the control group). Of the 495 implanted subjects, 476 (96.2%; 476/495) (315 in the SBL-3 group and 161 in the control group) completed the study at the Form 5A (1-year post-operative) visit. Table 8 describes the subject accountability.

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Table 8: Subject Accountability (Intent to Treat Population, ITT) (Primary Eyes)

| SBL-3 | | | | | | Control | | | | |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
| | Form 1 | Form 2 | Form 3A | Form 4A | Form 5A | Form 1 | Form 2 | Form 3A | Form 4A | Form 5A |
| Expected^{1} (E) | 333 | 333 | 333 | 333 | 333 | 166 | 166 | 166 | 166 | 166 |
| Not Due^{2}(ND) | 3 | 3 | 3 | 3 | 3 | 0 | 0 | 0 | 0 | 0 |
| Missed (M) | 0 | 1 | 3 | 2 | 0 | 0 | 1 | 3 | 0 | 0 |
| Discontinued (D) | 1 | 1 | 3 | 5 | 10 | 0 | 0 | 0 | 1 | 2 |
| Lost-to-Follow up (L) | 0 | 0 | 0 | 2 | 5 | 0 | 0 | 0 | 2 | 3 |
| Visit in Window (VW) | 329 | 322 | 317 | 289 | 302 | 166 | 163 | 159 | 148 | 154 |
| Visit Not in Window (VN) | 0 | 6 | 7 | 32 | 13 | 0 | 2 | 4 | 15 | 7 |
| Total Accountability (%)^{3} | 100.0 | 99.7 | 99.1 | 98.8 | 98.4 | 100.0 | 99.4 | 98.2 | 98.8 | 98.2 |
| 1. Expected = all eyes randomized (ITT) | | | | | | | | | | |
| 2. Not Due = not attempted. Attempted but aborted are discontinued by the Form 1 Visit | | | | | | | | | | |
| 3. Total Accountability = (VW+VN)/(E-ND-D) displayed as a percentage. | | | | | | | | | | |

## C. Study Population Demographics and Baseline Parameters

The demographics of the study population are typical for this type of study performed in the US, as shown in Table 9. Those subjects having cataractous natural lenses tend to be 60 years or older in age. Historically, a greater proportion of women enroll in these types of clinical trials. Also, they tend to be dominated by white, non-Hispanic individuals.

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Table 9: Subject Demographics (ITT Population)

| Characteristic | Statistics | SBL3 (N=333) | Control (N=166) | p-value^{1} |
| --- | --- | --- | --- | --- |
| Age | n | 333 | 166 | |
| | Mean (Std) | 67.7 (7.54) | 67.9 (6.94) | 0.7583 |
| | Median | 68.3 | 68.8 | |
| | Range | 34.6, 88.8 | 45.2, 82.0 | |
| < 60 yr | n (%) | 54 (16.2) | 19 (11.4) | 0.2681 |
| 60 - <70 yr | n (%) | 137 (41.1) | 78 (47.0) | |
| ≥ 70 yr | n (%) | 142 (42.6) | 69 (41.6) | |
| Gender | | | | |
| Male | n (%) | 111 (33.3) | 58 (34.9) | 0.7209 |
| Female | n (%) | 222 (66.7) | 108 (65.1) | |
| Race | | | | |
| Black or African American | n (%) | 20 (6.0) | 7 (4.2) | 0.1594 |
| American Indian or Alaska Native | n (%) | 0 (0.0) | 0 (0.0) | |
| Asian | n (%) | 1 (0.3) | 0 (0.0) | |
| Native Hawaiian/Pacific Islander | n (%) | 0 (0.0) | 0 (0.0) | |
| White | n (%) | 312 (93.7) | 157 (94.6) | |
| Other | n (%) | 0 (0.0) | 2 (1.2) | |
| Ethnicity | | | | |
| Hispanic or Latino | n (%) | 11 (3.3) | 5 (3.0) | 0.8619 |
| Not Hispanic or Latino | n (%) | 322 (96.7) | 161 (97.0) | |
| | | | | |
| 1. P-value associated with Chi-Square tests for categorical variables, and 2-sample t-tests for continuous variables
2. Observed rate % = (N/n)*100 | | | | |

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D. Safety and Effectiveness Results

1. Safety Results

The analysis of safety was based on the safety cohort of 496 subjects which had the IOL come into contact with the eye (330 in the SBL-3™ group and 166 in the control group). The post-operative adverse event rates are based upon the number of eyes implanted. The key safety outcomes for this study are presented below in Tables 10 to 24.

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

**Cumulative and Persistent Adverse Events- Safety Population- All Eyes**

Table 10 outlines the incidences of cumulative and persistent adverse events for the SBL-3™ and Akreos AO (control) monofocal IOL as compared to the ISO 11979-7:2018 for the safety population- All Eyes, the entire study cohort.

The incidence rates of cumulative adverse events for the SBL-3™ compared favorably to the specified ISO SPE (historical control) rates, as the observed rates for SBL-3™ were within or not statistically significantly higher than the specified ISO SPE rates, except for Secondary Surgical Intervention rate which is explained below. There were twelve observed cases of Secondary Surgical Interventions (1.8%; 12/656) which is statistically inferior to the historical control SPE rate. However, only six of the SSI were related to the optical properties of the IOL (0.9%; 6/656). Subsequently, the remaining 6 SSI (0.9%; 6/656) were not related to the IOL optical properties at all and were treatments for SAE's.

The incidence rates of persistent adverse events for the SBL-3™ also compared favorably to the specified ISO SPE rates. There was one case of corneal stromal edema (0.2%; 1/628), however, this rate was not statistically significantly higher than the ISO SPE rate of 0.3%. Furthermore, the SBL-3™ had one case of cystoid macular edema (0.2%; 1/628), and this rate was not statistically significantly higher than the ISO SPE rate of 0.5%

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a Per ISO 11979-7 2018 Ophthalmic Implants- Intraocular Lenses (Part 7): The SPE rate is the safety and performance endpoint.
b The maximum number of cases that would not be significantly higher than the historical SPE rate, based upon a 1-sided

Table 10: Cumulative and Persistent Adverse Events, All Eyes, Safety Population, Primary Safety Endpoint

| | SBL-3™ N=656 | | | Akreos N=332 | | |
| --- | --- | --- | --- | --- | --- | --- |
| ISOa SPE Rate (%) | Maxb No. of Cases allowed before SPE rate exceeded | Observed | Observedd Rate | Maxb No. of Cases allowed before SPE rate exceeded | Observed Number | Observed Rate |
| | | Number (n) | (%) | | (n) | (%) |
| | | | | | | |
| 3 | 27 | 13 | 2 | 15 | 9 | 2.7 |
| 0.3 | 4 | 0 | 0 | 3 | 0 | 0 |
| 0.1 | 2 | 0 | 0 | 1 | 0 | 0 |
| 0.1 | 2 | 0 | 0 | 1 | 0 | 0 |
| 0.1 | 2 | 1 | 0.2 | 1 | 0 | 0 |
| 0.3 | 4 | 1 | 0.2 | 3 | 0 | 0 |
| 0.8 | 9 | 12 | 1.8c | 6 | 3 | 0.9 |
| | SBL-3™ n=628 | | | Akreos n=322 | | |
| 0.3 | 4 | 1 | 0.2 | 3 | 0 | 0 |
| 0.5 | 6 | 1 | 0.2 | 4 | 0 | 0 |
| 0.3 | 4 | 0 | 0 | 3 | 0 | 0 |
| 0.4 | 5 | 0 | 0 | 3 | 0 | 0 |

hypothesis test using an alpha of 0.05.
cThe observed rate for Secondary Surgical Intervention is statistically inferior (p &lt; 0.05) to the historical control SPE rate.
d Observed rate % = (N/n)*100

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# Secondary Surgical Intervention Related to Optical Properties of the IOL

The cumulative rate of secondary surgical interventions (SSIs) related to the optical properties of the IOL were reported during the clinical trial. The results are based on the safety population- All Eyes. A total of 6 SBL-3™ SSIs related to and not related to the optical properties of the IOL out of 656 SBL-3™ implanted are shown below in Tables 11-13. Two subjects had explants (both eyes for one subject, primary eye for second subject) due to the subjective complaints of dissatisfaction with visual symptoms (or level of vision). Two additional subjects (both eyes for one subject, primary eye for second subject) had IOL rotation due to dissatisfaction with vision (visual disturbances and decreased vision). The confidence interval on the difference in the rates includes zero, and therefore there was no statistically significant difference between the arms in the rates for the SSIs related to optical properties.

Table 11: Secondary Surgical Interventions (SSI) Related to the Optical Properties of the IOL, All Eyes, Safety Population

| Eye | Statistic | SBL3TM | Akreos | SBL3TM - Akreos |
| --- | --- | --- | --- | --- |
| All Eyes | N | 656 | 332 | |
| | n | 6 | 0 | 6 |
| | % | 0.91 | 0 | 0.91 |
| | 90% CI | 0.40, 1.80 | 0.00, 0.90 | -0.01, 1.76 |
| Percentages are calculated as (n/N)*100;CI=Confidence Interval (exact) | | | | |
| N and % for treatment difference column are based on observed differences between groups | | | | |

There were six (6) SBL-3™ cases of SSI not related to the optical properties of the IOL during this study. The SSIs were treatments for SAE's; there were no SSIs as the original event.

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Table 12: Secondary Surgical Interventions (SSI) Not Related to the Optical Properties of the IOL, All Eyes, Safety Population

| Secondary Surgical Interventions: Not Device Related | Treatments for SAE's |
| --- | --- |
| SBL-3TM | Yag iridotomy for pupillary block |
| SBL-3TM | Haptic malposition at surgery lead to IOL repositioning |
| SBL-3TM | Vitrectomy for retinal detachment |
| SBL-3TM | DMEK for corneal edema |
| SBL-3TM | IOL explant for IOL incorrect power |
| SBL-3TM | Yag vitreolysis |

Table 13: Characterization of SSI based on the Modified Version of AAO Consensus (Masket, 2017) Safety Population.

| All Eyes | | Statistic | SBL-3TM | Akreos | SBL-3TM - Akreos |
| --- | --- | --- | --- | --- | --- |
| Exchange | | N | 656 | 332 | |
| | | n | 1 | 0 | 1 |
| | | % | 0.15 | 0.00 | 0.05 |
| | | 95% CI | 0.00, 0.28 | 0.00, 0.37 | -0.05, 0.15 |
| Removal | | N | 656 | 332 | |
| | | n | 3 | 0 | 3 |
| | | % | 0.46 | 0.00 | 0.15 |
| | | 95% CI | 0.03, 0.44 | 0.00, 0.37 | -0.02, 0.32 |
| Repositioning | | N | 656 | 332 | |
| | | n | 4 | 1 | 3 |
| | | % | 0.61 | 0.30 | 0.10 |
| | | 95% CI | 0.06, 0.52 | 0.00, 0.56 | -0.18, 0.38 |
| | | | | | |
| | Percentages are calculated as (n/N)*100;CI=Confidence Interval (exact) | | | | |
| | N and % for treatment difference column are based on observed differences between groups | | | | |

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# Cumulative and Persistent Adverse Events- Safety Population-Primary Eyes

Table 14 outlines the incidences of cumulative and persistent adverse events for the SBL-3™ and Akreos AO (control) monofocal IOL as compared to the ISO 11979-7:2018 for the safety population- Primary Eyes.

The incidence rates of cumulative adverse events for the SBL-3™ (primary eyes) compared favorably to the specified ISO SPE rates, as the observed rates for SBL-3™ were within or not statistically significantly higher than the specified ISO SPE rates, except for Secondary Surgical Intervention rate which is explained below. There were seven observed cases of Secondary Surgical Interventions (2.1%, 7/330) which is statistically inferior to the historical control SPE rate. However, only 3 of the SSI were related to the optical properties of the IOL (0.9%; 3/330) and are discussed below.

The incidence rates of persistent adverse events for the SBL-3™ (primary eyes) also compared favorably to the specified ISO SPE rates. There was one case of cystoid macular edema (0.3%; 1/315), however, this rate was not statistically significantly higher than the ISO SPE rate of 0.5%.

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Table 14: Cumulative and Persistent Adverse Events, Primary Eyes, Safety Population, Primary Safety Endpoint

| | | SBL-3™ N=330 | | | Akreos N=166 | | |
| --- | --- | --- | --- | --- | --- | --- | --- |
| | | | | | | | |
| | ISO SPEaRate (%) | Max No. of Casesballowed before SPE rate exceeded | Observed Number (n) | ObserveddRate (%) | Max No. of Casesballowed before SPE rate exceeded | Observed Number (n) | ObserveddRate (%) |
| Cumulative Serious Adverse Events | | | | | | | |
| Cystoid Macular Edema | 3 | 15 | 7 | 2.1 | 9 | 4 | 2.4 |
| Hypopyon | 0.3 | 3 | 0 | 0 | 2 | 0 | 0 |
| Endophthalmitis | 0.1 | 1 | 0 | 0 | 1 | 0 | 0 |
| Lens Dislocated from Posterior Chamber | 0.1 | 1 | 0 | 0 | 1 | 0 | 0 |
| Pupillary Block | 0.1 | 1 | 0 | 0 | 1 | 0 | 0 |
| Retinal Detachment | 0.3 | 3 | 1 | 0.3 | 2 | 0 | 0 |
| SSI (excluding posterior capsulotomy) | 0.8 | 6 | 7 | 2.1c | 3 | 0 | 0 |
| Persistent Serious Adverse Events | | SBL-3™ N=315 | | | Akreos N=161 | | |
| Corneal Stromal Edema | 0.3 | 3 | 0 | 0 | 2 | 0 | 0 |
| Cystoid Macular Edema | 0.5 | 4 | 1 | 0.3 | 2 | 0 | 0 |

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| Iritis | 0.3 | 3 | 0 | 0 | 2 | 0 | 0 |
| --- | --- | --- | --- | --- | --- | --- | --- |
| Raised IOP Requiring Treatment | 0.4 | 3 | 0 | 0 | 2 | 0 | 0 |

a Per ISO 11979-7 2018 Ophthalmic Implants- Intraocular Lenses (Part 7): The SPE rate is the safety and performance endpoint.
b The maximum number of cases that would not be significantly higher than the historical SPE rate, based upon a 1-sided hypothesis test using an alpha of 0.05.
c The observed rate for Secondary Surgical Intervention is statistically inferior (p &lt; 0.05) to the historical control SPE rate.
d Observed rate % = (N/n)*100

## Secondary Surgical Intervention Related to Optical Properties of the IOL-Primary eyes

The cumulative rate of secondary surgical interventions (SSIs) related to the optical properties of the IOL were reported during the clinical trial. The results are based on the safety population- Primary Eyes. A total of 3 SBL-3™ SSIs related to the optical properties of the IOL out of 330 SBL-3™ implanted are shown below in Table 15. The confidence interval on the difference in the rates includes zero, and therefore there was no statistically significant difference between the arms in the rates for the SSIs related to optical properties. This confirms a successful outcome.

Table 15: Secondary Surgical Interventions Related to the Optical Properties of the IOL, Primary Eyes, Safety Population

| Secondary Surgical Intervention Due to Optical Properties of the IOL Safety Population | | | | |
| --- | --- | --- | --- | --- |
| Eye | Statistic | SBL-3™ | Akreos | SBL-3™ - Akreos |
| Primary Eye | N | 330 | 166 | |
| | n | 3 | 0 | 3 |
| | % | 0.91 | 0 | 0.91 |
| | 90% CI | 0.25, 2.33 | 0.00, 1.79 | -0.78, 2.25 |
| Percentages are calculated as (n/N)*100;CI=Confidence Interval (exact) | | | | |
| N and % for treatment difference column are based on observed differences between groups | | | | |

Another characterization of this is provided below in Table 16.

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Table 16: Supportive Characterization of Secondary Surgical Interventions Based on a Modified Version of AAO Consensus (Masket,2017) Safety Population-Primary Eyes

| Primary Eye | Statistic | SBL-3^{TM} | Akreos | SBL-3^{TM} - Akreos |
| --- | --- | --- | --- | --- |
| Exchange | N | 330 | 166 | |
| | n | 1 | 0 | 1 |
| | % | 0.30 | 0.00 | 0.30 |
| | 95% CI | 0.01, 1.68 | 0.00, 2.20 | -0.29, 0.90 |
| Removal | N | 330 | 166 | |
| | n | 1 | 0 | 1 |
| | % | 0.30 | 0.00 | 0.30 |
| | 95% CI | 0.01, 1.68 | 0.00, 2.20 | -0.29, 0.90 |
| Repositioning | N | 330 | 166 | |
| | n | 3 | 0 | 3 |
| | % | 0.91 | 0.00 | 0.91 |
| | 95% CI | 0.19, 2.63 | 0.00, 2.20 | -0.11, 1.93 |
| Percentages are calculated as (n/N)*100;CI=Confidence Interval (exact) | | | | |
| N and % for treatment difference column are based on observed differences between groups | | | | |

## Proportion of Eyes Achieving Best Corrected Distance Visual Acuity (BCDVA) of 0.30 LogMar (or better)

An 'other' supportive safety endpoint was the proportion of SBL-3™ eyes achieving BCDVA 0.3 LogMAR or better vs. ISO 11979-7:2018 (E) SPE (historical control) rate at 6 months and 1 year. Table E.4 historical grid summary for posterior chamber IOLs is presented in Table 15 for both treatment groups by primary eye, fellow eye and all eyes from the safety population for overall post-operative BCDVA 0.30 LogMar or better. Table 17 is the best-case population. (This is defined as all patients/eyes from the All-Implanted population who have at least one postoperative visit without any clinically significant preoperative pathology or macular degeneration at any time.)

SBL-3™ eyes achieved BCDVA of 0.3 LogMAR or better at 6 months and 1 year exceeding the ISO rates for posterior chamber lenses (92.5% overall), with ranges of 98.1% (6-month primary eyes; 315/321) to 99.7% (1-year fellow eyes; 312/313).

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Note: The clinical protocol initially contained an error in the instructions for how to perform the testing for BCDVA. See the discussion below “Table 38: Best Corrected Distance Visual Acuity (LogMar) (by analysis population)” in the “Effectiveness Results” section.

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Table 17: Rates of Overall Post-Operative BCVA of 0.30 LogMAR or Better relative to Historical Grid noted at any Time, Safety Population

| | | SBL3 | | | | Akreos | | |
| --- | --- | --- | --- | --- | --- | --- | --- | --- |
| Visual Acuity1 | ISO SPE Rate (%) | Total (N) | Minimum No. of Cases allowed before less than SPE Rate | Observed Number (n) | | Total (N) | Minimum No. of Cases allowed before less than SPE Rate | Observed Number (n) |
| Overall post-operative BCVA 0.3 LogMar or better - Primary Eye | | | | | | | | |
| Visit 4A | 92.5 | 321 | 289 | 315 | | 163 | 145 | 162 |
| Visit 5A | 92.5 | 315 | 283 | 313 | | 161 | 143 | 160 |
| Overall post-operative BCVA 0.3 LogMar or better - Fellow Eye | | | | | | | | |
| Visit 4A | 92.5 | 318 | 286 | 316 | | 163 | 145 | 163 |
| Visit 5A | 92.5 | 313 | 282 | 312 | | 161 | 143 | 161 |
| Overall post-operative BCVA 0.3 LogMar or better - All Eyes | | | | | | | | |
| Visit 4A | 92.5 | 639 | 580 | 631 | | 326 | 294 | 325 |
| Visit 5A | 92.5 | 628 | 570 | 625 | | 322 | 290 | 321 |
| | | | | | | | | |
| Note: For subjects without a 4A or 5A visit due to early discontinuation, the last available visit after surgery is used. | | | | | | | | |
| Note: % = (n/N)*100 | | | | | | | | |

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Table 18 shows best case SBL-3™ eyes achieved BCDVA of 0.30 LogMAR or better at 6 months and 1 year exceeding the ISO rates for posterior chamber lenses (96.7% best-case), with ranges of 98.1% (6-month primary eyes; 314/320) to 99.7% (1-year fellow eyes; 311/312).

Table 18: Rates of Overall Post-Operative BCDVA of 0.30 LogMAR or Better relative to Historical Grid noted at any Time, Best Case

| | | SBL3 | | | | Akreos | | |
| --- | --- | --- | --- | --- | --- | --- | --- | --- |
| Visual Acuity1 | ISO SPE Rate (%) | Total (N) | Minimum No. of Cases allowed before less than SPE Rate | Observed Number (n) | | Total (N) | Minimum No. of Cases allowed before less than SPE Rate | Observed Number (n) |
| Overall post-operative BCVA 0.3 LogMar or better - Primary Eye | | | | | | | | |
| Visit 4A | 96.7 | 320 | 304 | 314 | | 162 | 153 | 161 |
| Visit 5A | 96.7 | 314 | 298 | 312 | | 160 | 151 | 159 |
| Overall post-operative BCVA 0.3 LogMar or better - Fellow Eye | | | | | | | | |
| Visit 4A | 96.7 | 317 | 301 | 315 | | 162 | 153 | 162 |
| Visit 5A | 96.7 | 312 | 296 | 311 | | 160 | 151 | 160 |
| Overall post-operative BCVA 0.3 LogMar or better - All Eyes | | | | | | | | |
| Visit 4A | 96.7 | 637 | 608 | 629 | | 324 | 308 | 323 |
| Visit 5A | 96.7 | 626 | 598 | 623 | | 320 | 304 | 319 |
| | | | | | | | | |
| Note: For subjects without a 4A or 5A visit due to early discontinuation, the last available visit after surgery is used. | | | | | | | | |
| Note: % = (n/N)*100 | | | | | | | | |

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Eyes Which Lost ≥ 10 Letters of BCDVA Between Postoperative Visits

The following Tables 19-20 present data on the number (and rates) in each arm of those eyes that had a loss of 10 or more letters, both in the all eyes group and the primary eyes group.

Table 19: Eyes which Presented with a Loss of 10 Letters or more- All Eyes

| Visit | Finding | SBL3 n (%) | Akreos n (%) | Estimate of Treatment Difference (Diff Prop (SE)) | 90% CI of Difference | p-value^{1} |
| --- | --- | --- | --- | --- | --- | --- |
| At Any Visit | N | 655 | 332 | | | |
| | Loss of ≥ 10 letters in BCDVA between any form evaluation and a prior form visit | 51 (7.8) | 35 (10.5) | -0.03 (0.020) | -0.06, 0.01 | 0.1523 |
| Form 4A | N | 643 | 326 | | | |
| | Loss of ≥ 10 letters in BCDVA between visit and any prior visit | 20 (3.1) | 11 (3.4) | -0.00 (0.012) | -0.02, 0.02 | 0.8474 |
| Form 5A | N | 628 | 322 | | | |
| | Loss of ≥ 10 letters in BCDVA between | 31 (4.9) | 26 (8.1) | -0.03 (0.017) | -0.06, -0.00 | 0.0608 |

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At the 1-year post-operative visit, a greater proportion of the control group (8.1%; 26/322) showed this loss in the primary eye than the SBL-3™ group (4.9%; 31/628), but this difference was not significant.

Table 20: Eyes which Presented with a Loss of 10 Letters or More- Primary Eyes

| Visit | Finding | SBL3 n (%) | Akreos n (%) | "Estimate of Treatment Difference (Diff Prop (SE))" | 90% CI of Difference | p-value^{1} |
| --- | --- | --- | --- | --- | --- | --- |
| At Any Visit | N | 329 | 166 | | | |
| | Loss of > 10 letters in BCDVA between any form evaluation and a prior form visit | 27 (8.2) | 16 (9.6) | -0.01 (0.028) | -0.06, 0.03 | 0.6138 |
| Form 4A | N | 322 | 163 | | | |
| | Loss of > 10 letters in BCDVA between visit and any prior visit | 9 (2.8) | 5 (3.1) | -0.00 (0.017) | -0.03, 0.02 | 1.0000 |
| Form 5A | N | 315 | 161 | | | |
| | Loss of > 10 letters in BCDVA between | 18 (5.7) | 11 (6.8) | -0.01 (0.024) | -0.05, 0.03 | 0.6865 |

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| | visit and any prior visit | | | | | |
| --- | --- | --- | --- | --- | --- | --- |
| 1. P-value associated with Fisher's Exact Test
Note: Comparisons are between any post-operative visit after 1 month (3A) and any prior visit. Unscheduled visits occurring between visits are counted as occurring at the next scheduled visit.
Note: % = (n/N)*100 | | | | | | |

Similar to the primary eyes, the all eyes data identified that the control group (6.8%; 11/161) had more subjects lose 10 or more letters at the 1-year post-operative visit than the SBL-3™ group (5.7%; 18/315). As with the primary eyes though, this difference was also not significant

## Serious Adverse Events of Types Not in the ISO Historical Control

Serious adverse events (of types not in the ISO historical control grid) were also evaluated, as described below in Table 21.

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Table 21: All Serious Non-Grid Rate Adverse Events

| All Serious Non-Grid Adverse Events
(Safety population - Either Eye) |
| --- |
| Category/Primary Term | SBL-3
(N-330)
n (%) | Akreos
(N-166)
n (%) | P-Value |
| TOTAL
CORNEAL STROMAL
EDEMA | 2 (0.6) | 0 (0.0) | 0.5538 |
| 2 (0.6) | 0 (0.0) | |
| EPITHELIOPATHY
TOTAL | | | |
| 1 (0.3) | 0 (0.0) | 1.0000 |
| EPITHELIAL DEFECT | 1 (0.3) | 0 (0.0) | |
| PUPIL
OBSERVATIONS
TOTAL | | | |
| 1 (0.3) | 0 (0.0) | 1.0000 |
| PUPILLARY
FINDINGS | 1 (0.3) | 0 (0.0) | |
| RETINOPATHY
TOTAL | | | |
| 2 (0.6) | 0 (0.0) | 0.5538 |
| EPIRETINAL
MEMBRANE
MACULOPATHY | 1 (0.3) | 0 (0.0) | |
| VITREOUS FINDINGS
TOTAL
SYNERESIS | | | |
| 0 (0.0) | 1 (0.6) | 0.3347 |
| 0 (0.0) | 1 (0.6) | |

There were no significant differences between the test and control IOLs in this comparison.

## Binocular Contrast sensitivity

Figures 5-12 present the secondary safety endpoint binocular contrast sensitivity performed under photopic and mesopic conditions with and without glare. Subjects were measured under photopic conditions with contrast sensitivity monitor luminance being calibrated with the M&amp;S Technologies Spyder

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photometer to approximately $85~\mathrm{cd} / \mathrm{m}^2$ and mesopic conditions to approximately 3 $\mathrm{cd} / \mathrm{m}^2$ with the use of a neutral density filter.

Figure 5: Contrast Sensitivity Outcomes, Photopic, without Glare at the 6-month Post-operative Visit

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Figure 6: Contrast Sensitivity Outcomes, Photopic, without Glare at the 1-year Post-operative Visit

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Figure 7: Contrast Sensitivity Outcomes, Photopic, with Glare at the 6-month Post-operative Visit
Photopic with Glare 6 Month Binocular

Figure 8: Contrast Sensitivity Outcomes, Photopic, with Glare at the 1-year Post-operative Visit
Photopic with Glare 1-year Binocular

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Figure 9: Contrast Sensitivity Outcomes, Mesopic, without Glare at the 6-month Post-operative Visit
Figure 10: Contrast Sensitivity Outcomes, Mesopic, without Glare at the 1-year Post-operative Visit


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Figure 11: Contrast Sensitivity Outcomes, Mesopic, with Glare at the 6-month Post-operative Visit
Figure 12: Contrast Sensitivity Outcomes, Mesopic, with Glare at the 1-year Post-operative Visit


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Below are descriptions of these outcomes in tabular form.

Table 22: Photopic Contrast Sensitivity Outcomes without and with Glare at the 1-year Post-operative Visit

| Spatial Frequency | IOL Model | N | Photopic without Glare | | | N | Photopic w/Glare | | |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
| | | | Mean | Subjects who did not see the reference pattern | | | Mean | Subjects who did not see the reference pattern | |
| | | | | n | % | | | n | % |
| 1.5 | SBL | | Not Tested | Not Tested | | Not Tested | Not Tested | | |
| | Akreos | | | | | | | | |
| | Difference | | | | | | | | |
| 3 | SBL | 313 | 2.042 | 0 | 0 | 312 | 1.788 | 0 | 0 |
| | Akreos | 158 | 2.199 | 0 | 0 | 158 | 1.927 | 0 | 0 |
| | Difference | | -0.157 | | | | -0.139 | | |
| 6 | SBL | 313 | 1.894 | 0 | 0 | 312 | 1.655 | 0 | 0 |
| | Akreos | 158 | 2.103 | 0 | 0 | 158 | 1.845 | 0 | 0 |
| | Difference | | -0.209 | | | | -0.19 | | |
| 12 | SBL | 313 | 1.49 | 0 | 0 | 312 | 1.294 | 0 | 0 |
| | Akreos | 158 | 1.695 | 0 | 0 | 158 | 1.489 | 0 | 0 |
| | Difference | | -0.205 | | | | -0.195 | | |
| 18 | SBL | 311 | 1.056 | 2 | 0.6 | 309 | 0.907 | 3 | 1 |
| | Akreos | 158 | 1.208 | 0 | 0 | 158 | 1.062 | 0 | 0 |
| | Difference | | -0.152 | | | | -0.155 | | |

Note: $\% = (\mathrm{n / N})^{*}100$

Table 23: Mesopic Contrast Sensitivity Outcomes without and with Glare at the 1-year post-operative Visit

| Spatial Frequency | IOL Model | N | Mesopic w/o Glare | | | N | Mesopic w/Glare | | |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
| | | | Mean | Subjects who did not see the reference pattern | | | Mean | Subjects who did not see the reference pattern | |
| | | | | n | % | | | n | % |
| 1.5 | SBL | 314 | 1.879 | 0 | 0 | 312 | 1.63 | 0 | 0 |
| | Akreos | 158 | 1.997 | 0 | 0 | 158 | 1.699 | 0 | 0 |
| | Difference | | -0.118 | | | | -0.069 | | |

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| 3 | SBL | 314 | 1.775 | 0 | 0 | 312 | 1.604 | 0 | 0 |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
| | Akreos | 158 | 1.997 | 0 | 0 | 158 | 1.769 | 0 | 0 |
| | Difference | | -0.222 | | | | -0.165 | | |
| 6 | SBL | 314 | 1.478 | 0 | 0 | 312 | 1.358 | 0 | 0 |
| | Akreos | 158 | 1.719 | 0 | 0 | 158 | 1.544 | 0 | 0 |
| | Difference | | -0.241 | | | | -0.186 | | |
| 12 | SBL | 314 | 0.896 | 0 | 0 | 310 | 0.808 | 2 | 0.6 |
| | Akreos | 158 | 1.04 | 0 | 0 | 158 | 0.965 | 0 | 0 |
| | Difference | | -0.144 | | | | -0.157 | | |
| 18 | SBL | | Not Tested | Not Tested | | | Not Tested | Not Tested | |
| | Akreos | | | | | | | | |

Note: $\% = (\mathrm{n / N})^{*}100$
Tables 22 and 23 show that under photopic and mesopic without glare, the mean difference between the SBL-3 and the Akreos AO is 0.181 log units and with glare, 0.140 log units. Under mesopic without glare, the mean difference is 0.181 log units and with glare, 0.144 log units.
Multifocal IOLs generally show somewhat reduced levels of contrast sensitivity compared to monofocal IOLs. All of the differences between the SBL-3™ and control arms for mean contrast sensitivity results, appear to be within within the general levels seen in other studies of marketed multifocal IOLs.

Other Safety Endpoint Outcomes

## Visual disturbances

Visual disturbances were assessed using a patient reported outcomes tool, which specifically asked subjects about their experience with blurry vision, vision in dim light, vision in bright light, seeing colors, seeing halos, seeing streaks, seeing glare and seeing double images. Subjects implanted with the SBL-3™ multifocal IOL reported higher rates of “severe” levels for halos, glare, streaks of light and multiple images, than subjects implanted with the monofocal control (See Tables 24 and 25).

The table below describes the outcomes at the pre-operative visit and the 6-month and 1-year post-operative visits.

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Table 24: Visual Disturbances Reported by Visit

| Visual Disturbance over the past 7 Days at Each Visit Safety Population | | | | |
| --- | --- | --- | --- | --- |
| Form 0 | SBL-3 | | Akreos AO | |
| | N | Mean | N | Mean |
| Blurry Vision | 330 | 6.27 | 165 | 6.44 |
| Dim Light | 330 | 6.14 | 165 | 6.44 |
| Bright Light | 330 | 5.74 | 165 | 6.61 |
| Colors | 330 | 3.84 | 165 | 4.07 |
| Halos | 330 | 5.35 | 165 | 5.66 |
| Streaks of Light | 330 | 5.13 | 165 | 5.47 |
| Glare | 330 | 6.20 | 165 | 6.75 |
| Double Images | 330 | 6.20 | 165 | 6.75 |
| | | | | |
| Form 4A | SBL-3 | | Akreos AO | |
| | N | Mean | N | Mean |
| Blurry Vision | 319 | 2.83 | 163 | 2.16 |
| Dim Light | 320 | 1.81 | 163 | 2.07 |
| Bright Light | 320 | 3.56 | 163 | 3.71 |
| Colors | 320 | 0.78 | 163 | 0.67 |
| Halos | 320 | 2.93 | 163 | 1.38 |
| Streaks of Light | 320 | 2.75 | 163 | 1.41 |
| Glare | 320 | 3.03 | 163 | 1.65 |
| Double Images | 320 | 1.69 | 163 | 0.42 |
| | | | | |
| Form 5A | SBL-3 | | Akreos AO | |
| | N | Mean | N | Mean |
| Blurry Vision | 314 | 2.43 | 161 | 2.43 |
| Dim Light | 314 | 1.69 | 161 | 2.03 |
| Bright Light | 314 | 3.30 | 161 | 3.43 |
| Colors | 314 | 0.70 | 161 | 0.76 |
| Halos | 314 | 2.43 | 161 | 1.47 |

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Subjects reported their visual symptoms on the visual disturbance questionnaire as 'None' (0), 'Mild' (1-3), 'Moderate' (4-6) and 'Severe' (&gt;6). Overall, the rate of test subjects reporting their symptoms as 'none' increased between 4A and 5A for all visual disturbance questions (sensitivity to light remained similar between 4A and 5A) while the control subjects experienced a decreased rate across 7 of the 8 questions posed.

Additionally, the opposite trend was noted for the rate of test subjects reporting their symptoms as 'severe' decrease between 4A and 5A visits for 6 of the 8 visual disturbance questions (with their rates decreasing) while the control group generally showed an increase in severe symptoms for 6 of the 8 visual disturbance questions.

This data was also tabulated for each of the potential responses for each group, at the 4A and 5A visits.

Table 25: Visual Disturbances Data for all Subjects who Responded with each Possible Response Option for each Item

| Visual Disturbance Questionnaire (PRO-VDS) at 4A Safety Population | | | | Visual Disturbance Questionnaire (PRO-VDS) at 5A Safety Population | | | |
| --- | --- | --- | --- | --- | --- | --- | --- |
| | SBL3 n (%) | | Akreos n (%) | | SBL3 n (%) | | Akreos n (%) |
| | Overall | | Overall | | Overall | | Overall |
| Question 1 Blurry Vision | | | | Question 1 Blurry Vision | | | |
| N | 319 | | 163 | N | 314 | | 161 |
| None (0) | 86 (26.96) | | 58 (35.58) | None (0) | 99 (31.53) | | 50 (31.06) |
| Mild (1-3) | 130 (40.75) | | 68 (41.72) | Mild (1-3) | 129 (41.08) | | 67 (41.61) |
| Moderate (4-6) | 63 (19.75) | | 24 (14.72) | Moderate (4-6) | 49 (15.61) | | 27 (16.77) |

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| Severe (>6) | 40
(12.54) | | 13
(7.98) | Severe (>6) | 37
(11.78) | | 17
(10.56) |
| --- | --- | --- | --- | --- | --- | --- | --- |
| | | | | | | | |
| | SBL3
n (%) | | Akreos
n (%) | | SBL3
n (%) | | Akreos
n (%) |
| | Overall | | Overall | | Overall | | Overall |
| Question 2 Difficulty in Low Light | | | | Question 2 Difficulty in Low Light | | | |
| N | 320 | | 163 | N | 314 | | 161 |
| None (0) | 156
(48.75) | | 72
(44.17) | None (0) | 160
(50.96) | | 73
(45.34) |
| Mild (1-3) | 101
(31.56) | | 55
(33.74) | Mild (1-3) | 98
(31.21) | | 55
(34.16) |
| Moderate (4-6) | 37
(11.56) | | 18
(11.04) | Moderate (4-6) | 27
(8.60) | | 17
(10.56) |
| Severe (>6) | 26
(8.13) | | 18
(11.04) | Severe (>6) | 29
(9.24) | | 16
(9.94) |
| | | | | | | | |
| | SBL3
n (%) | | Akreos
n (%) | | SBL3
n (%) | | Akreos
n (%) |
| | Overall | | Overall | | Overall | | Overall |
| Question 3 Sensitivity to Bright Light | | | | Question 3 Sensitivity to Bright Light | | | |
| N | 320 | | 163 | N | 314 | | 161 |
| None (0) | 82
(25.63) | | 30
(18.40) | None (0) | 81
(25.80) | | 38
(23.60) |
| Mild (1-3) | 101
(31.56) | | 59
(36.20) | Mild (1-3) | 119
(37.90) | | 59
(36.65) |
| Moderate (4-6) | 64
(20.00) | | 36
(22.09) | Moderate (4-6) | 45
(14.33) | | 26
(16.15) |
| Severe (>6) | 73
(22.81) | | 38
(23.31) | Severe (>6) | 69
(21.97) | | 38
(23.60) |
| | | | | | | | |
| | SBL3
n (%) | | Akreos
n (%) | | SBL3
n (%) | | Akreos
n (%) |
| | Overall | | Overall | | Overall | | Overall |
| Question 4 Difficulty to see colors | | | | Question 4 Difficulty to see colors | | | |

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| N | 320 | | 163 | N | 314 | | 161 |
| --- | --- | --- | --- | --- | --- | --- | --- |
| None (0) | 227(70.94) | | 122(74.85) | None (0) | 234(74.52) | | 120(74.53) |
| Mild (1-3) | 71(22.19) | | 32(19.63) | Mild (1-3) | 60(19.11) | | 27(16.77) |
| Moderate (4-6) | 12(3.75) | | 7(4.29) | Moderate (4-6) | 12(3.82) | | 10(6.21) |
| Severe (>6) | 10(3.13) | | 2(1.23) | Severe (>6) | 8(2.55) | | 4(2.48) |
| | | | | | | | |
| | SBL3n (%) | | Akreosn (%) | | SBL3n (%) | | Akreosn (%) |
| | Overall | | Overall | | Overall | | Overall |
| Question 5Disruption due toHalos | | | | Question 5Disruption due toHalos | | | |
| N | 320 | | 163 | N | 314 | | 161 |
| None (0) | 102(31.88) | | 103(63.19) | None (0) | 125(39.81) | | 93(57.76) |
| Mild (1-3) | 119(37.19) | | 33(20.25) | Mild (1-3) | 104(33.12) | | 43(26.71) |
| Moderate (4-6) | 42(13.13) | | 16(9.82) | Moderate (4-6) | 41(13.06) | | 12(7.45) |
| Severe (>6) | 57(17.81) | | 11(6.75) | Severe (>6) | 44(14.01) | | 13(8.07) |
| | | | | | | | |
| | SBL3n (%) | | Akreosn (%) | | SBL3n (%) | | Akreosn (%) |
| | Overall | | Overall | | Overall | | Overall |
| Question 6 Seeingstreaks or rays oflight | | | | Question 6 Seeingstreaks or rays oflight | | | |
| N | 320 | | 163 | N | 314 | | 161 |
| None (0) | 118(36.88) | | 100(61.35) | None (0) | 142(45.22) | | 82(50.93) |
| Mild (1-3) | 106(33.13) | | 37(22.70) | Mild (1-3) | 91(28.98) | | 55(34.16) |
| Moderate (4-6) | 37(11.56) | | 15(9.20) | Moderate (4-6) | 30(9.55) | | 12(7.45) |
| Severe (>6) | 59(18.44) | | 11(6.75) | Severe (>6) | 51(16.24) | | 12(7.45) |

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| | | | | | | |
| --- | --- | --- | --- | --- | --- | --- |
| | SBL3 n (%) | | Akreos n (%) | | SBL3 n (%) | |
| | Overall | | Overall | | Overall | |
| Question 7 Glare from headlights/streetlights | | | | Question 7 Glare from headlights/streetlights | | |
| N | 320 | | 163 | N | 314 | |
| None (0) | 94 (29.38) | | 87 (53.37) | None (0) | 108 (34.39) | |
| Mild (1-3) | 120 (37.50) | | 49 (30.06) | Mild (1-3) | 113 (35.99) | |
| Moderate (4-6) | 47 (14.69) | | 14 (8.59) | Moderate (4-6) | 34 (10.83) | |
| Severe (>6) | 59 (18.44) | | 13 (7.98) | Severe (>6) | 59 (18.79) | |
| | | | | | | |
| | SBL3 n (%) | | Akreos n (%) | | SBL3 n (%) | |
| | Overall | | Overall | | Overall | |
| Question 8 Seeing double or multiple images | | | | Question 8 Seeing double or multiple images | | |
| N | 320 | | 163 | N | 314 | |
| None (0) | 192 (60.00) | | 139 (85.28) | None (0) | 204 (64.97) | |
| Mild (1-3) | 67 (20.94) | | 17 (10.43) | Mild (1-3) | 62 (19.75) | |
| Moderate (4-6) | 29 (9.06) | | 5 (3.07) | Moderate (4-6) | 20 (6.37) | |
| Severe (>6) | 32 (10.00) | | 2 (1.23) | Severe (>6) | 28 (8.92) | |

Note: $\% = (\mathrm{n / N})^{*}100$
The same trends were noted for this tabulation as well. More test subjects reported noticing halo, glare and double images

## Fundus Visulation

At the 1-year post-operative visit, the safety population included 628 SBL- $3^{\mathrm{TM}}$ eyes and 322 control IOL eyes. In that group, it was noted that the

PMA P200020: FDA Summary of Safety and Effectivenes…