IC-8 Apthera Intraocular Lens (IOL)

P210005 · Acu Focus, Inc. · POE · Jul 22, 2022 · Ophthalmic

Device Facts

• Record ID: P210005
• Device Name: IC-8 Apthera Intraocular Lens (IOL)
• Applicant: Acu Focus, Inc.
• Product Code: POE · Ophthalmic
• Decision Date: Jul 22, 2022
• Decision: APPR
• Regulation: 21 CFR 886.3600
• Device Class: Class 3
• Attributes: Therapeutic

Intended Use

The IC-8® Apthera™ IOL is indicated for unilateral implantation for the visual correction of aphakia and to create monovision in patients of age 22 or older who have been diagnosed with bilateral operable cataract, who have up to 1.5 D of astigmatism in the implanted eye, and who do not have a history of retinal disease and who are not predisposed to experiencing retinal disease in the future. The device is intended for primary implantation in the capsular bag, in the non-dominant eye, after the fellow eye has already undergone successful implantation (uncorrected distance visual acuity of 20/32 or better and best-corrected distance visual acuity of 20/25 or better) of a monofocal or monofocal toric IOL that is targeted for emmetropia. The refractive target for the IC-8® Apthera™ IOL should be -0.75 D. The lens mitigates the effects of presbyopia by providing an extended depth of focus. Compared to an aspheric monofocal or monofocal toric IOL, the lens provides improved intermediate and near visual acuity, while maintaining comparable distance visual acuity.

Device Story

One-piece, UV-blocking, foldable hydrophobic acrylic IOL; features centrally embedded FilterRing™ (PVDF with carbon nanoparticles) with small central aperture (1.36 mm) to extend depth of focus; anterior surface aspheric; posterior surface 360° square edge. Surgically implanted into capsular bag by ophthalmologist to replace cataractous lens. Small aperture increases depth of focus; mitigates presbyopia. Healthcare provider uses slit-lamp and standard ophthalmic exams to monitor. Output is improved intermediate/near vision; patient benefits from reduced spectacle dependence. Requires careful patient selection due to potential for visual disturbances (glare, halo, starburst) and challenges in retinal visualization/YAG laser capsulotomy.

Clinical Evidence

Prospective, multi-center, open-label, non-randomized clinical study (N=453; 343 IC-8, 110 Control). Primary endpoints: monocular BCDVA, ocular adverse event rates, IOL removal rates. Results: IC-8 group showed statistical superiority in binocular UCIVA and UCNVA, non-inferiority in binocular UCDVA. Monocular DCIVA superior in IC-8 eyes. Depth of focus improved by 0.91 D. Adverse events compared to ISO SPE rates; no IC-8 IOL removals during study. Contrast sensitivity reduced in IC-8 eyes monocularly but comparable binocularly.

Technological Characteristics

Material: UV-blocking hydrophobic acrylic (≤4% water content). FilterRing: PVDF with carbon nanoparticles (12 μg). Optic: 6.0 mm diameter, biconvex, aspheric, 360° square edge. Haptics: Modified C-loop, 5° angulation. Overall diameter: 12.5 mm. Refractive index: 1.483 at 35°C. Sterilization: Gamma radiation. Complies with ISO 11979-5, ISO 11979-3, ISO 10993-1.

Indications for Use

Indicated for unilateral implantation in patients age 22+ with bilateral operable cataract and up to 1.5 D astigmatism in the implanted eye. Contraindicated in patients with history of or predisposition to retinal disease and dilated pupil size < 7.0 mm.

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

• AcrySof® IQ (monofocal/toric)
• TECNIS® aspheric monofocal (SA60WF or ZCB00)
• TECNIS® monofocal toric (SA6AT3, SA6AT4, ZCT150 or ZCT225)

Submission Summary (Full Text)

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SUMMARY OF SAFETY AND EFFECTIVENESS DATA (SSED)

I. GENERAL INFORMATION

Device Generic Name: Hydrophobic Acrylic Small Aperture Intraocular Lens (IOL)
Device Trade Name: IC-8® Apthera™ IOL
Device Product Code: Extended Depth of Focus Intraocular Lens (POE)
Applicant’s Name and Address: AcuFocus, Inc.
32 Discovery, Suite 200
Irvine, CA 92618
Date(s) of Panel Recommendation: None
Premarket Approval Application (PMA) Number: P210005
Date of FDA Notice of Approval: July 22, 2022

II. INDICATIONS FOR USE

The IC-8® Apthera™ IOL is indicated for unilateral implantation for the visual correction of aphakia and to create monovision in patients of age 22 or older who have been diagnosed with bilateral operable cataract, who have up to 1.5 D of astigmatism in the implanted eye, and who do not have a history of retinal disease and who are not predisposed to experiencing retinal disease in the future. The device is intended for primary implantation in the capsular bag, in the non-dominant eye, after the fellow eye has already undergone successful implantation (uncorrected distance visual acuity of 20/32 or better and best-corrected distance visual acuity of 20/25 or better) of a monofocal or monofocal toric IOL that is targeted for emmetropia. The refractive target for the IC-8® Apthera™ IOL should be -0.75 D. The lens mitigates the effects of presbyopia by providing an extended depth of focus. Compared to an aspheric monofocal or monofocal toric IOL, the lens provides improved intermediate and near visual acuity, while maintaining comparable distance visual acuity.

III. CONTRAINDICATIONS

1. Patients with dilated pupil size less than 7.0 mm.
2. Patients with a history of retinal disease including but not limited to, high myopia, diabetes, macular disease, sickle cell disease, retinal tear, retinal detachment, retinal vein occlusion, ocular tumor, uveitis, and patients who are predisposed to experiencing retinal disease in the future.

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# IV. WARNINGS AND PRECAUTIONS

The warnings and precautions can be found in the labeling for the IC-8 Apthera intraocular lens.

# V. DEVICE DESCRIPTION

The IC-8 Apthera IOL is a one-piece, UV-blocking, foldable IOL that provides an extended depth of focus. Made from an implantable medical grade hydrophobic acrylic material with ≤4% water content, the IC-8 Apthera IOL is designed to be surgically implanted into the human eye (placed into the capsular bag) to replace a cataractous crystalline lens. The IC-8 Apthera IOL is an aspheric monofocal IOL that features a centrally embedded FilterRing™ component (mask) with a small central aperture. The FilterRing component is composed of polyvinylidene fluoride (PVDF) and nanoparticles of carbon. Carbon black nanoparticles represent 12 μg of the device mass. This small aperture FilterRing component is designed to extend the depth of focus. The anterior optic surface is aspheric, incorporating negative spherical aberration. The posterior surface of the IC-8 Apthera IOL is designed with a 360° square edge. The IC-8 Apthera IOL is supplied sterile for single-use only.

The IC-8 Apthera IOL has modified C-haptics, angled at 5 degrees, with an overall nominal diameter of 12.5 mm. The biconvex aspheric optic measures 6.00 mm in diameter and is ultraviolet absorbent with the hydrophobic acrylic material having an index of refraction of 1.483 at 35°C. The embedded FilterRing component has an outer diameter of 3.23 mm and an inner diameter of 1.36 mm, creating a central aperture that is intended to increase the depth of focus. The FilterRing component is 5.0 μm in thickness and contains 3,200 microperforations that are arranged in a pseudo-random fashion (sparing the periphery to optimize filter integrity while manufacturing) and range in size from 7 to 10 μm diameters. Table 1 and Figure 1 provide a detailed description and physical characteristics of the IC-8 Apthera IOL. Figure 2 displays the spectral transmittance of the lens compared with a natural human crystalline lens. Figure 3 displays the modulation transfer function (MTF) of the lens compared to a monofocal lens.

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Figure 1. Physical Characteristics of the IC-8 Apthera IOL

Table 1. Device Design Characteristics

| Material | UV-blocking hydrophobic acrylic |
| --- | --- |
| Power | +10.0 D through +30.0 D in 0.5 D increments |
| Optic diameter (ØB) | 6.0 mm |
| Overall diameter (ØT) | 12.5 mm |
| Optic design | Biconvex, aspheric anterior surface, and 360° posterior square edge |
| Haptic design | Modified C-loop haptic with 5° angulation |
| Refractive index | 1.483 at 35°C and 589 nm |
| Spherical Aberration | -0.22 mm |
| Light transmission | UV cut-off at 10% Transmittance (T) for a typical 20.0 diopter IC-8 Apthera IOL is shown in Figure 2 |
| FilterRing component material | Polyvinylidene fluoride (PVDF) with carbon nanoparticles |
| FilterRing component outer diameter | 3.23 mm |
| FilterRing component aperture diameter | 1.36 mm |
| Number of micro-perforations | 3,200 |
| FilterRing component Thickness | 5 mm |

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| A-Constant for Ultrasound Biometry: | 120.15 |
| --- | --- |
| Optical Surgeon Factor | 2.64 |
| Ultrasound Surgeon Factor | 2.44 |

Figure 2: Spectral Transmittance

# Legend:

Curve 1: Spectral Transmittance (T) curve of a typical 20.0 diopter IC-8 Apthera IOL, UV cut-off at $10\%$ T is $375~\mathrm{nm}$ .

Curve 2: Spectral Transmittance (T) curve corresponding to a 53 year-old phakic eye

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Figure 2. Modulation Transfer Function (MTF) Through-Focus Response of +23.0 D IOLs in a Model Eye (Green Light, 50 lp/mm, 3 mm Aperture)

The IC-8 Apthera IOL complies with all specified International Organization for Standardization (ISO) 11979-5 physicochemical testing requirements that are relevant to IOLs.

The IC-8 Apthera IOL is packaged in an integrated twist-cap lens holder with a bromobutyl rubber stopper that screws onto a $5\mathrm{mL}$ glass vial filled with water for injection (WFI). The vial is then placed in an IOL blister tray to minimize movement of the glass vial in the blister tray during transit and sealed with a Tyvek lid. The assembled glass vial units are then sterilized by gamma radiation in a validated sterilization cycle. Following sterilization, the device is placed in a chipboard unit carton.

# VI. ALTERNATIVE PRACTICES AND PROCEDURES

Patients who undergo cataract removal presently have several non-surgical and surgical alternatives for restoring functional vision of the aphakic eye. Non-surgical options include special cataract glasses or contact lenses. Surgical options include implantation of monofocal, multifocal, extended depth of focus, or accommodative IOLs. 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.

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VII. MARKETING HISTORY

The IC-8 Apthera IOL is currently commercially available in the European Union/European Economic Area, United Kingdom, Australia, New Zealand, Argentina, El Salvador, and Singapore. The IC-8 Apthera IOL has not been withdrawn from any country for any reason, including for safety and effectiveness.

VIII. POTENTIAL ADVERSE EFFECTS OF THE DEVICE ON HEALTH

Potential adverse effects (e.g., complications) associated with the use of the device include the following:

- The presence of capsular rupture or radial capsular tears known or suspected at the time of surgery
- Surgical difficulties at the time of cataract extraction, which may increase the potential for complications (e.g., persistent bleeding, significant iris damage, uncontrolled positive pressure, or significant vitreous prolapse or loss)
- Zonular damage
- Endophthalmitis/intraocular infection
- Secondary surgical intervention
- Raised intraocular pressure requiring treatment
- Iritis/vitritis
- Corneal stromal edema
- Hypopyon
- Retinal detachment/retinal tear
- Cystoid macular edema
- IOL dislocation
- Pupillary block
- Retained crystalline lens fragment
- Increased visual symptoms (compared to a monofocal IOL) related to the optical characteristics of the IOL, including glare, halo, starbursts
- Lens epithelial cell down-growth
- Corneal endothelial damage
- Hyphema
- Pigment dispersion
- Posterior capsular opacity
- Glaucoma
- Iris prolapse
- Cyclitic membrane

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Secondary surgical interventions include, but are not limited to: implant repositioning, removal, vitrectomy, iridectomy for pupillary block, would leak repair, retinal detachment repair, aqueous tap.

For the specific adverse events that occurred in the IC-8 Apthera IOL clinical study conducted in the United States, please see Section X below.

## IX. SUMMARY OF NONCLINICAL STUDIES

Non-clinical studies with the IC-8 Apthera IOL and the IC-8 Apthera IOL packaging components, supporting the safety and effectiveness of the IC-8 Apthera IOL, are summarized below.

### Biocompatibility Testing

Biocompatibility testing was conducted using sterile finished IC-8 Apthera IOLs packaged in vials in accordance with ISO 11979-5, Ophthalmic implants - Intraocular lenses - Part 5: Biocompatibility and 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: Test for local effects after implantation, and - Part 10: Tests for irritation and sensitization standards. Results are summarized below in Table 2.

All biocompatibility tests were conducted in accordance with provisions of 21 CFR 58, Good Laboratory Practice (GLP) for Nonclinical Laboratory Studies.

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Table 2. IC-8 Apthera IOL – Biocompatibility Testing

| Test | Purpose | Acceptance Criteria | Results |
| --- | --- | --- | --- |
| ISO Elution Method (ISO 10993-5) | Evaluates the cellular toxicity potential of the device in vitro | Non-cytotoxic | Pass |
| Direct Contact Method (ISO 10993-5) | Evaluates the cellular toxicity potential of the device in vitro | Non-cytotoxic | Pass |
| Guinea Pig Maximization (ISO 10993-10) | Evaluate the potential of sensitization | Non-sensitizer | Pass |
| Bacterial Reverse Mutation Test (Ames test) (ISO 10993-3) | Evaluate the potential of implant to cause mutagenic changes | Non-mutagenic | Pass |
| Mouse Lymphoma Assay (ISO 10993-3) | Evaluate the mutagenic potential of the implant | Non-mutagenic | Pass |
| Four- Week Muscle Implantation Study in Rabbits (ISO 10993-6) | Evaluate the local tissue response and local effects of the IOL | No significant local response | Pass |
| Six- Month Intraocular Implantation Study in Rabbits (ISO 11979-5) | Evaluate local effects in ocular tissue | No significant biological intraocular response | Pass |

Under typical clinical conditions, the FilterRing component remains embedded within the acrylic material and does not have tissue contact. Therefore, the FilterRing component was not tested separately for biocompatibility.

## Physicochemical Testing

The physicochemical tests were conducted using sterile finished IC-8 Apthera IOLs packaged in vials to evaluate the physicochemical properties and stability of the IOL material that is relevant to its biocompatibility, and to provide evidence of compliance to ISO 11979-5 and ISO 10993-1 standards. All physicochemical testing met the acceptance criteria defined in the respective test protocols. The tests and results are summarized in Table 3.

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Table 3. IC-8 Apthera IOL – Physicochemical Testing

| Test | Purpose | Acceptance Criteria | Results |
| --- | --- | --- | --- |
| Exhaustive Extraction | To quantify extractable additives and other extractable substances | No appreciable extractables from the test article when the test article is subjected to exhaustive extraction in hexane and water. | Pass |
| Leachables | Analyze for leachables under simulated physiological conditions | No appreciable leachables for water extraction. | Pass |
| Hydrolytic Stability | Test to verify material does not degrade by hydrolysis | No appreciable extractables, changes in spectral transmittance or dioptric power of the test article after exposure in aqueous condition for 5 years (simulated). | Pass |
| Photostability | Ensure that exposure to light does not cause photochemical degradation | No significant changes to the lens material, UV/Visible spectra, dioptric power, image quality, and. no appreciable chemical components leached after (simulated) 20 years of UV exposure to the test article. | Pass |
| Nd:YAG Laser Exposure | Test to evaluate material stability when exposed to neodymium-doped yttrium aluminum garnet (Nd:YAG) laser treatment, and no leakage of toxic components | No appreciable extractables and cytotoxicity of the extractant. | Pass |
| Insoluble Inorganics | Assess the presence of residual inorganic material | No appreciable detection of inorganic insoluble residuals. | Pass |

## Optical Testing

In order to predict the quality of vision with the implantation of the IC-8 Apthera IOL, optical bench testing was undertaken in accordance with ISO 11979-2. The optical testing met the criteria in accordance with ISO 11979-2 standard. The tests and results are summarized in Table 4.

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Table 4. IC-8 Apthera IOL - Optical Testing

| Test | Purpose | Acceptance criteria | Results |
| --- | --- | --- | --- |
| Dioptric Power and Image Quality | To assess accuracy of optical power, meet minimum image quality specifications | Described in ISO 11979-2 | Pass |
| Spectral Transmittance | To characterize the spectral transmittance of the IOL | N/A | Characterized |
| Depth of Focus | To characterize the depth of focus of the IOL | N/A | Characterized |

# Mechanical Testing

Mechanical testing of the IC-8 Apthera IOL was conducted to establish the optomechanical integrity of the IC-8 Apthera IOL as well as to predict the quality of vision after implantation of the IOL.

Testing was conducted following the guidelines of ISO 11979-3:2012, Ophthalmic implants- Intraocular lenses - Part 3: Mechanical properties and test methods. The mechanical testing met the criteria in accordance with the ISO 11979-3 standard. The tests and results are summarized in Table 5.

Table 5. IC-8 Apthera IOL - Mechanical Testing

| Test | Purpose | Acceptance Criteria | Results |
| --- | --- | --- | --- |
| 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 | Characterized |
| 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 |
| Angle of Contact | To characterize haptic contact with ocular tissues | N/A | Characterization |
| Compression Force Decay | To characterize the face to compress the | N/A | Characterization |

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| Test | Purpose | Acceptance Criteria | Results |
| --- | --- | --- | --- |
| | IOL after 24 hours decay | | |
| Dynamic Fatigue Durability | To assess the ability of the haptics to withstand cyclic compressive loading | No haptic breakage | Pass |
| Surgical Manipulation | To assess the force to separate the haptic from the optic | Greater than or equal to 0.25 N | Pass |
| Dimensions, Surface, & Homogeneity | To assess conformance to dimensional tolerances and free of surface defects | Multiple acceptance criteria described in ISO 11979-3 | Pass |
| Evaluation of the IC-8 IOL Following Simulated Surgical Manipulation | To assess the ability of the IOL to withstand simulated surgical implantation without damage | Multiple acceptance criteria described in ISO 11979-3 | Pass |

## Microbiology, Sterilization, and Shelf Life Testing

The sterilization process of the IC-8 Apthera IOL was validated per FDA-recognized ISO 11137-1,2,3 using the VDmax25 approach. The process has a sterility assurance level (SAL) of $10^{-6}$. The sterilization dose audits and associated test reports including validated sterility, bioburden, and endotoxin test data passed all acceptance criteria per applicable standards and guidances.

Accelerated shelf-life data equivalent to 6 months real time shelf-life data support a 6-month shelf life.

The microbiology, sterilization, and shelf-life tests were conducted in accordance with the following standards:

- ISO 11137 Sterilization of health care products — Radiation — Part 1, 2 and 3.
- United States Pharmacopeia (USP) &lt;71&gt; Sterility Test.
- ANSI/AAMI/ST72:2019 Bacterial endotoxins — Test methods, routine monitoring, and alternatives to batch testing.
- European Pharmacopoeia (EP) 2.6.14. Bacterial endotoxins.
- ISO 11607, Packaging for terminally sterilized medical devices — Part 1 and 2.
- ISO 11979-8:2006/Amd.1:2011 Ophthalmic implants — Intraocular lenses — Part 8: Fundamental requirements.

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- ISO 11979-6:2014 Ophthalmic implants — Intraocular lenses — Part 6: Shelf-life and transport stability testing.
- ASTM F88/F88M-15 Standard Test Method for Seal Strength of Flexible Barrier Materials.
- ASTM F1929-15, Standard Test Method for Detecting Seal Leaks in Porous Medical Packaging by Dye Penetration
- ASTM-F2096 Standard Test Method for Detecting Gross Leaks in Medical Packaging by Internal Pressurization (Bubble Leak Test)

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: IC-8 Apthera 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 ISO 11737. | Limit ≤30 CFU/lens | Pass |
| Gamma irradiation sterilization (used VDmax25 approach) | Validates that the gamma irradiation sterilization is effective per ISO 11137-1,2,3. | Achieve SAL of 10-6 | Pass |
| Sterility test | Validates post-sterilization sterility of the device per USP 71 | No microbial growth | Pass |
| Bacterial Endotoxin Testing (performed per EP 2.6.14. and ANSI/AAMI/S T72:2019) | Confirm product is non-pyrogenic per ISO 11979-8:2017 and the FDA guidance. | <0.2 EU/device | Pass |
| Package Integrity Testing – Legibility of Labeling | Confirm that product labeling remains legible after sterilization during stability studies per ISO 11979-6. | Label remains legible | Pass |
| Package Integrity Testing – | Assesses transport stability per ISO 11979-6. | No defects | Pass |

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| Assessment of physical damage | | | |
| --- | --- | --- | --- |
| Packaging Integrity Testing – Bubble Leak | Confirm that product seal integrity is maintained after sterilization during stability studies per ISO 11979-6 and ASTM-F2096 | No gross leaks | Pass |
| Packaging Integrity Testing – Seal Closure Strength | Confirm that product seal strength is maintained after sterilization during stability studies per ISO 11979-6 and ASTM F88-15 | Minimum seal strength to be <1.2N/15mm | Pass |
| Packaging Integrity Testing – Dye Penetration | Confirm that product seal integrity is maintained after sterilization during stability studies per ISO 11979-6 and ASTM F1929-15 | No channel leaks | Pass |

X. SUMMARY OF PRIMARY CLINICAL STUDY

The applicant performed a clinical study to establish a reasonable assurance of safety and effectiveness of the IC-8 Apthera IOL (referred to as IC-8 IOL). This study was conducted in the United States under Investigational Device Exemption (IDE) G180075 (Clinical Evaluation of a Small Aperture Extended Depth of Focus Intraocular Lens). 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

Subjects were treated between December 2018 and August 2019. The database for this PMA reflected data collected through October 2020 and included 453 bilaterally implanted subjects. There were available data from 21 investigational sites.

The study was a prospective, multi-center, open-label, parallel-group, non-randomized, and examiner masked, 12-month study conducted to evaluate the safety and effectiveness of the IC-8 IOL. The objective of this study was to evaluate the safety and effectiveness of the IC-8 device in providing increased depth of focus and improved intermediate and near visual acuity compared to an aspheric monofocal IOL.

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In accordance with the device's indication, the study was designed for unilateral implantation of the IC-8 IOL. The IC-8 group (also referred to as the Test group) consisted of subjects implanted with the IC-8 IOL in one eye (IC-8 eye) and a monofocal or monofocal toric IOL in the fellow eye, with a monovision refractive target. The Control group consisted of subjects bilaterally implanted with a monofocal or monofocal toric IOL, with both eyes targeted for emmetropia. Fellow eyes in the IC-8 group and both eyes in the Control group could be implanted with an AcrySof® IQ or TECNIS® aspheric monofocal (SA60WF or ZCB00), or monofocal toric IOL (SA6AT3, SA6AT4, ZCT150 or ZCT225), all marketed alternatives to the IC-8 IOL with similar indications for use except that they do not provide an extended depth of focus and are not intended to provide improved vision at intermediate and near distances. All study subjects were required to be implanted in the first eye with a monofocal/monofocal toric IOL, with a refractive target of emmetropia. So long as the first eye achieved satisfactory visual outcomes at postoperative week one, the second eye could be implanted with either the IC-8 IOL or a control device, depending on which study arm the subjects was in. Second eyes implanted with the IC-8 IOL were targeted for a slightly myopic outcome (-0.75D). Second eyes implanted with a control device were targeted for emmetropia. If the predicted residual refractive cylinder was $\geq 0.75$ D and a toric IOL was not indicated, limbal relaxing incisions (LRI's) were permitted to be performed for minimization of residual astigmatism during initial surgery, only in monofocal eyes in the test and the control groups. LRI's were not permitted in eyes implanted with the IC-8 IOL.

Statistical analyses were frequentist. For the key effectiveness analyses, three hypothesis tests were to demonstrate statistical superiority over the control group with respect to binocular uncorrected intermediate visual acuity (UCIVA), binocular uncorrected near visual acuity (UCNVA), and monocular distance-corrected intermediate visual acuity (DCIVA). An additional non-inferiority hypothesis was used to demonstrate non-inferiority of the test group compared to the control group with respect to binocular uncorrected distance visual acuity (UCDVA).

Study sample sizes are based on Annex B of ISO 11979-7:2014 with 300 evaluable total test subjects needed at one year for evaluation of safety endpoints versus Safety and Performance Endpoints (SPE) rates, particularly for adverse event and best-corrected distance visual acuity (BCDVA) evaluations. A total of 355 IC-8 group subjects and 120 Control group subjects were planned for enrollment to ensure 300 IC-8 group subjects and 100 Control group subjects would complete one-year follow-up and be available for analysis. The sample size assumed an approximate $10\%$ attrition rate over the duration of the one-year study and an additional $5\%$

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disqualification rate for the first eye.

For the co-primary effectiveness endpoints of binocular UCIVA, binocular UCNVA, binocular UCDVA and monocular DCIVA, a two-sided two-sample t-test with $\alpha = 0.05$ and standard deviation (SD) of 1.6 lines was estimated to provide over $99\%$ power to detect at least a 1-line difference in mean visual acuity between IC-8 group subjects (or IC-8 eyes) and Control subjects (or Control eyes).

## 1. Clinical Inclusion and Exclusion Criteria

Enrollment in the study was limited to subjects who met the following inclusion criteria (all criteria apply to each eye):

1. Minimum 22 years of age
2. Able to comprehend and have signed a statement of informed consent
3. Availability, willingness, ability and sufficient cognitive awareness to comply with examination procedures and study visits
4. Planned crystalline lens removal by phacoemulsification, with or without femtosecond laser-assisted extraction, and posterior chamber IOL implantation in both eyes
5. Cataractous lens changes as demonstrated by BCDVA of 20/40 or worse either with or without a glare source present
6. Potential for postoperative BCDVA of 20/25 or better in each eye after cataract removal and IOL implantation as estimated by an instrument such as a Potential Acuity Meter (PAM) or surgeon investigator estimation
7. Clear intraocular media, other than cataract

Subjects were not permitted to enroll in the study if they met any of the following exclusion criteria (all criteria apply to each eye):

1. Requiring an IC-8 intraocular lens outside the available spherical power range of +15.5 D to +27.5 D
2. Pharmacologically dilated pupil size less than $6\mathrm{mm}$ in either eye
3. Inability to achieve stable keratometric readings for contact lens wearers (difference in corneal astigmatism between two visits at least 1 week apart following discontinuation of contact lens wear is within $\pm 0.50$ diopter in magnitude and within $\pm 15^{\circ}$ in axis)
4. Subjects with irregular astigmatism in either eye
5. Preoperative corneal astigmatism $&gt;1.50$ diopters in either eye (as assessed by biometry keratometric readings)
6. Active or recurrent anterior segment pathology (chronic uveitis, iritis, iridocyclitis, rubeosis iridis, Reiter's syndrome, etc.)

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7. Presence of ocular abnormalities other than cataract such as:
a. Corneal abnormalities other than regular corneal astigmatism up to 1.50 diopters
b. Pupil abnormalities
c. Strabismus or amblyopia
d. Capsular or zonular abnormalities
e. Glaucomatous retinal nerve fiber changes
f. Recurrent and/or persistent intraocular inflammation
g. Known pathology that may affect visual acuity and/or is predicted to cause future acuity losses to a level of worse than 20/25 BCDVA (e.g., macular degeneration)

8. Diagnosis of dry eye in which subjects are unable to maintain eye comfort or adequate vision even with dry eye medication

9. Congenital bilateral cataracts

10. Previous corneal or intraocular surgery, except pterygium surgery, which may be allowed, based on meeting all other inclusion/exclusion criteria

11. History of ocular trauma or ocular conditions expected to require retinal laser treatment or other surgical intervention

12. Use of systemic or ocular medications that may affect vision or likely to impact pupil dilation or iris structure, such as any prior or current use of tamsulosin or silodosin (alpha-adrenergic antagonist medications, e.g., Flomax, Flomaxtra, Rapaflo), which are likely to cause poor dilation or lack of adequate iris structure to perform standard cataract surgery

13. Acute, chronic, or uncontrolled systemic disease that would, in the opinion of the investigator, increase the operative risk or confound the outcomes of the study (e.g., immune compromised, connective tissue disease, hypertension, Type I &amp; II diabetes etc.)

14. Use of antipsychotic and/or anti-depressant medication within the last 6 months, or plan/need to use such medications during the course of the study, which could increase the operative risk or confound the outcome(s) of the study in the opinion of the investigator

15. Patient is pregnant, plans to become pregnant, is lactating or has another condition associated with hormonal fluctuation that could lead to refractive changes and dry eye

16. Concurrent participation or participation in any clinical trial up to 30 days prior to preoperative visit

Additionally, subjects implanted with a monofocal/monofocal toric IOL in the first eye had to meet the following postoperative criteria within the 1-week to 1-month (7 to 45 days) window from first eye surgery, in order to qualify for implantation in

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the second eye:

- 20/32 or better UCDVA and 20/25 or better BCDVA (or Snellen equivalent)
- No ongoing ocular adverse events
- Normal corneal health as assessed by slit lamp biomicroscopy (corneal edema Grade 1+ or less and superficial punctate keratitis (SPK) Grade 1 or less)

If during the implantation of the IOL, a surgical complication such as a capsular bag tear/rupture or zonular damage/rupture occurred, the IC-8 IOL should not have been implanted.

# 2. Follow-up Schedule

All subjects were scheduled to return for follow-up examinations postoperatively at the time points described in Table 7. Up to 12 study visits were planned to complete treatment and assessment of either eye, or both eyes (depending upon the timing of the visit). Specific examinations and scheduled clinical assessments are presented in Table 8.

Table 7. Follow-up Visit Schedule

| Visit | Eyes evaluated | Visit Window |
| --- | --- | --- |
| Preoperative | Both eyes | ≤ 60 days prior to 2ndeye operative visit |
| 1steye Operative | 1steye | Recommended ≤ 15 days from preoperative visit |
| 2ndeye Operative | 2ndeye | ≤ 45 days following 1steye operative visit; after qualifying 1steye |
| 1 Day Postoperative | 1steye or 2ndeye | 1-2 days following operative visit for each eye |
| 1 Week Postoperative | 1steye or 2ndeye | 7-14 days following operative visit for each eye |
| 1 Month Postoperative | 1steye, 2ndeye, or both eyes | 20 - 45 days following operative visit for each eye |
| 3 Months Postoperative | Both eyes | 60 - 110 days following 2ndeye operative visit |
| 6 Months Postoperative | Both eyes | 160 - 210 days following 2ndeye operative visit |
| 12 Months Postoperative | Both eyes | 300 - 420 days following 2ndeye operative visit |

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Table 8. Clinical Evaluations

| Clinical Evaluation | Illumination | Testing | Group | Pre-op | Op* | Day 1** | Wk 1** | Mon 1** | Mon 3 | Mon 6 | Mon 12 |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
| Ocular & Health History | N/A | N/A | Both | X | | X | X | X | X | X | X |
| Cover Test | N/A | N/A | Both | X | | | | | | | |
| Sighting Eye Dominance | N/A | N/A | Both | X | | | | | X | | |
| Pupil Size | Photopic
Mesopic
Dilated | Monocular (OD & OS)
Monocular (OD & OS)
Monocular (OD & OS) | Both | X
X
X | | | | | X
X
X^A | X
X
X | X
X
X |
| Swinging Flash Light Test | N/A | Monocular (OD & OS) | Both | X | | | | | X | | |
| Biometry Measurements | N/A | Monocular (OD & OS) | Both | X | | | | | | | |
| Corneal Topography | N/A | Monocular (OD & OS) | Both | X | | | | | | X | X |
| Uncorrected Distance Visual Acuity (UCDVA) | Photopic | Monocular (OD & OS)
Binocular (OU) | Both | X
X | | M | M | M | M
M | M
M | M
M |
| Uncorrected Intermediate Visual Acuity (UCIVA) | Photopic | Monocular (OD & OS)
Binocular (OU) | Both | | | | | | M
M | M
M | M
M |
| Uncorrected Near Visual Acuity (UCNVA) | Photopic | Monocular (OD & OS)
Binocular (OU) | Both | X
X | | | | | M
M | M
M | M
M |
| Manifest Refraction | Photopic | Monocular (OD & OS) | Both | X | | | M | M | M | M | M |
| Add (Near) | Photopic | Monocular (OD & OS) | Both | | | | | | | M | |
| Distance-Corrected Distance Visual Acuity (DCDVA) | Photopic | Monocular (OD & OS)
Binocular (OU) | Both | X | | | M | M | M
M | M
M | M
M |
| Distance-Corrected Intermediate Visual Acuity (DCIVA) | Photopic | Monocular (OD & OS)
Binocular (OU) | Both | | | | | | M
M | M
M | M
M |
| Distance-Corrected Near Visual Acuity (DCNVA) | Photopic | Monocular (OD & OS)
Binocular (OU) | Both | | | | | | M
M | M
M | M
M |

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| Clinical Evaluation | Illumination | Testing | Group | Pre-op | Op* | Day 1** | Wk 1** | Mon 1** | Mon 3 | Mon 6 | Mon 12 |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
| Defocus Curve Test | Photopic | Monocular (OD & OS)
Binocular (OU) | Both | | | | | | M
M | | |
| +0.75 D Distance Corrected Distance Visual Acuity (+0.75 DCDVA) | Photopic | Monocular (2^{nd} eye)
Binocular (OU) | Both | | | | | | | M
M | |
| +0.75 D Distance Corrected Intermediate Visual Acuity (+0.75 DCIVA) | Photopic | Monocular (2^{nd} eye)
Binocular (OU) | Both | | | | | | | M
M | |
| +0.75 D Distance Corrected Near Visual Acuity (+0.75 DCNVA) | Photopic | Monocular (2^{nd} eye)
Binocular (OU) | Both | | | | | | | M
M | |
| Near Stereoacuity (w/ UCNVA; & w/ DCNVA with Add) | Photopic | Binocular | Both | | | | | | | X | |
| Slit-Lamp Exam (SLE) | N/A | Monocular (OD & OS) | Both | X | | X | X | X | X | X | X |
| IOL Centration & Tilt w/ SLE | N/A | Monocular (OD & OS) | Both | | | X | X | X | X | X | X |
| Toric IOL axis w/ SLE | N/A | Monocular (OD & OS) | Both | | | X^{C} | X^{C} | X^{C} | X^{C} | X^{C} | X^{C} |
| TBUT | N/A | Monocular (OD & OS) | Both | X | | | | | X | X | X |
| Corneal Staining | N/A | Monocular (1^{st} eye)
Monocular (2^{nd} eye) | Both | X
X | | | X | X^{D} | X
X | X
X | X
X |
| Intraocular Pressure | N/A | Monocular (OD & OS) | Both | X | | X | X | X | X | X | X |
| Gonioscopy | N/A | Monocular (OD & OS) | Both | X | | | | | | X | |
| Dilated Fundus Exam (BIO) | N/A | Monocular (OD & OS) | Both | X | | | | | | | X |
| Dilated Slit-lamp Exam | N/A | Monocular (OD & OS) | Both | X | | | | | | | X |
| Dilated Ocular Coherence Tomography (OCT) | N/A | Monocular (OD & OS) | Both | X | | | | | | | |
| Patient Reported Outcome Questionnaire(s) | N/A | N/A | Both | X | | | | | X | X | X |

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| Clinical Evaluation | Illumination | Testing | Group | Pre-op | Op* | Day 1** | Wk 1** | Mon 1** | Mon 3 | Mon 6 | Mon 12 |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
| Non-directed Question | N/A | N/A | Both | X | | X | X | X | X | X | X |
| CONTRAST SENSITIVITY SUBGROUP ONLY — CONTRAST SENSITIVITY AND LOW CONTRAST ACUITY TESTING | | | | | | | | | | | |
| Distance Contrast Sensitivity (w/ glare & w/o glare) | Photopic Mesopic | Monocular (OD & OS) Binocular (OU) | Both | | | | | | | M^{A}
M^{A} | M^{B}
M^{B} |
| 10% contrast UCDVA | Photopic | Monocular (2^{nd} eye) Binocular (OU) | Both | | | | | | | M^{A}
M^{A} | M^{B}
M^{B} |
| 10% contrast UCIVA | Photopic | Monocular (2^{nd} eye) Binocular (OU) | Both | | | | | | | M^{A}
M^{A} | M^{B}
M^{B} |
| 10% contrast UCNVA | Photopic | Monocular (2^{nd} eye) Binocular (OU) | Both | | | | | | | M^{A}
M^{A} | M^{B}
M^{B} |
| 10% contrast DCDVA | Photopic | Monocular (2^{nd} eye) Binocular (OU) | Both | | | | | | | M^{A}
M^{A} | M^{B}
M^{B} |
| 10% contrast DCIVA | Photopic | Monocular (2^{nd} eye) Binocular (OU) | Both | | | | | | | M^{A}
M^{A} | M^{B}
M^{B} |
| 10% contrast DCNVA | Photopic | Monocular (2^{nd} eye) Binocular (OU) | Both | | | | | | | M^{A}
M^{A} | M^{B}
M^{B} |
| RETINAL DIAGNOSTIC TESTING SUBGROUP ONLY — SUBGROUP-SPECIFIC RETINAL DIAGNOSTIC TESTING | | | | | | | | | | | |
| Undilated Threshold Visual Field Testing (Central 30-2) | Photopic | Monocular (OD & OS) | Test | X^{A} | | | | | X^{A} | | |
| Dilated Ocular Coherence Tomography (OCT) Images | N/A | Monocular (OD & OS) | Test | X^{A} | | | | | X^{A} | | |
| Dilated Fundus Photography | N/A | Monocular (OD & OS) | Test | X^{A} | | | | | X^{A} | | |

* Op (operative) visits are repeated for each eye’s surgery and the associated tests are performed on that operated eye only.
** Day 1, Week 1 and Month 1 visits are repeated after each eye’s surgery and the associated tests are performed on the most recently operated eye only.
A Subgroup testing only. Group sizes are specified in the statistical analysis plan.

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B Repeated at the 12-month visit for those subjects that have had a posterior capsulotomy procedure after the 6-month visit.
C Repeated at postop visits if medically indicated as determined by investigator.
D Repeated at 1 month visit if needed.
X Tests to be performed by non-masked examiner; M = tests to be performed by masked examiner.

## 3. Clinical Endpoints

With regard to safety,

- The co-primary safety endpoints were:
- Monocular BCDVA in the IC-8 eyes at 12 Months
- Rates of ocular adverse events (cumulative or persistent) through 12 Months compared to ISO Safety and Performance Endpoint (SPE) rates for posterior chamber IOLs
- Rate of IC-8 IOL removals due to visual/optical reasons cumulative through 12 Months

- The secondary safety endpoint was:
- Contrast sensitivity at 6 Months

With regard to success/failure safety criteria,

- The co-primary safety criteria were:
- Mean monocular BCDVA in IC-8 eyes is statistically non-inferior to that of the fellow control eyes using a non-inferiority margin of 0.10 logMAR
- The proportion of IC-8 eyes achieving BCDVA 0.30 logMAR or better is not less than the SPE rate listed in ISO 11979-7:2014 Table B.3
- The proportion of Best-Case IC-8 eyes achieving BCDVA 0.30 logMAR or better is not less than the SPE rate listed in ISO 11979-7:2014 Table B.4
- For each type of adverse event listed in the ISO 11979-7:2014 Table B.2, the rate for the IC-8 eyes is not statistically greater than the SPE rate for that event
- Descriptive statistics (mean, two-sided 90% confidence interval) for the rates of all key adverse events including but not limited to adverse events per ISO 11979-7:2014, adverse events that may be specifically related to the extended depth of focus (EDF) IOL design, e.g., related to the optical characteristics of the IOL, and any other significant ocular adverse events

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- Rate of IC-8 IOL removals due to visual/optical reasons in the IC-8 eyes is &lt; 3.1%. The one-sided 95% upper confidence limit of the rate (using exact binomial distribution) must be less than 3.1% to claim statistical success.

- The secondary safety criteria were:
- Descriptive statistics for photopic and mesopic contrast sensitivity with and without glare. Both monocular (between-eye difference between IC-8 eyes and their fellow control eyes) and binocular (test group versus control group) contrast sensitivity were evaluated.

All co-primary safety endpoints need to be achieved to claim overall safety success.

With regard to **effectiveness**.

- The co-primary effectiveness endpoints were:
- Mean photopic binocular UCIVA (66cm) for the test group compared to the control group at Month 6. The statistical success criterion was statistical superiority of the test group over the control group. The superiority margin was set at 0.00 logMAR. Clinical success criteria were: At least 50% of test subjects achieve 0.10 or better logMAR and at least 25% higher than the control subjects.
- Mean photopic binocular UCNVA (40cm) for the test group compared to the control group at Month 6. The statistical success criterion was statistical superiority of the test group over the control group. The superiority margin was set at 0.00 logMAR. Clinical success criteria were: At least 50% of test subjects achieve 0.30 or better logMAR and at least 25% higher than the control subjects.
- Mean photopic binocular UCDVA (4m) for the test group compared to the control group at 6 Months. The statistical success criterion was statistical non-inferiority of the test group over the control group. The non-inferiority margin was set at 0.10 logMAR. Clinical success criteria were: At least 50% of test subjects achieve 0.10 or better logMAR.
- Mean photopic monocular DCIVA (66cm) of the second eyes at 6 Months. The statistical success criterion was statistical superiority of the IC8 eyes compared to the second eyes in the control group. Clinical success criterion was: At least 50% of IC-8 eyes should achieve DCIVA of logMAR 0.2 or better.
- Mean photopic monocular distance-corrected depth of focus (DOF) of IC-8 eyes at 3 Months. Success criterion was: The mean DOF from IC-8 eyes is at least 0.5 D greater than the mean from the fellow control eyes at 0.2 logMAR visual acuity threshold.

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- The secondary effectiveness endpoint was:

- Performance of IC-8 in eyes with preoperative corneal astigmatism of &lt; 1.0D (Astigmatism Group 1) compared to eyes with preoperative corneal astigmatism of 1.0-1.5D (Astigmatism Group 2). This endpoint was analyzed at Month 3, using only IC-8 eyes that achieved BCDVA 20/25 at 3 Months. The statistical success criterion was: Mean UCDVA in Astigmatism Group 2 is non-inferior to Astigmatism Group 1, using a non-inferiority margin of 0.12 logMAR. The statistical analysis plan prespecified that analysis of this endpoint would not support a labeling claim that compared the IC-8 IOL to the monofocal or monofocal toric IOL.

## B. Accountability of PMA Cohort

At the time of database lock, of 453 subjects enrolled in the PMA study, 343 subjects in the IC-8 group were implanted with an IC-8 IOL in one eye and a monofocal/monofocal toric IOL in the fellow eye, and 110 enrolled subjects in the Control group were implanted in both eyes with monofocal/monofocal toric IOLs. The intent-to-treat (ITT) and safety populations both included 453 subjects (343 in the IC-8 group and 110 in the Control group). At the conclusion of the 12-month study, accountability was 98.8% (331/335) for the IC-8 group (Table 9) and 95.3% (101/106) for the Control group (Table 10).

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Table 9. IC-8 Group Subject Accountability (N=343) (n/N, %)

| | Day 1 (1st Eye) | Week 1 (1st Eye) | Month 1 (1st Eye) | Day 1 (2nd Eye) | Week 1 (2nd Eye) | Month 1 (2nd Eye) | Month 3 | Month 6 | Month 12 |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
| Active | 0/343 | 0/343 | 0/343 | 0/343 | 0/343 | 0/343 | 0/343 | 0/343 | 0/343 |
| | 0.0% | 0.0% | 0.0% | 0.0% | 0.0% | 0.0% | 0.0% | 0.0% | 0.0% |
| Available for Analysis | 343/343 | 343/343 | 342/343 | 342/343 | 343/343 | 341/343 | 340/343 | 335/343 | 331/343 |
| | 100.0% | 100.0% | 99.7% | 99.7% | 100.0% | 99.4% | 99.1% | 97.7% | 96.5% |
| Missing Subjects | 0/343 | 0/343 | 1/343 | 1/343 | 0/343 | 2/343 | 3/343 | 8/343 | 12/343 |
| | 0.0% | 0.0% | 0.3% | 0.3% | 0.0% | 0.6% | 0.9% | 2.3% | 3.5% |
| Discontinued* | 0/343 | 0/343 | 0/343 | 0/343 | 0/343 | 0/343 | 3/343 | 3/343 | 8/343 |
| | 0.0% | 0.0% | 0.0% | 0.0% | 0.0% | 0.0% | 0.9% | 0.9% | 2.3%** |
| Lost to follow-up | 0/343 | 0/343 | 0/343 | 0/343 | 0/343 | 0/343 | 0/343 | 3/343 | 4/343 |
| | 0.0% | 0.0% | 0.0% | 0.0% | 0.0% | 0.0% | 0.0% | 0.9%† | 1.2%† |
| Missed Visit | 0/343 | 0/343 | 1/343 | 1/343 | 0/343 | 2/343 | 0/343 | 2/343 | 0/343 |
| | 0.0% | 0.0% | 0.3% | 0.3% | 0.0% | 0.6% | 0.0% | 0.6% | 0.0% |
| Accountability | 343/343 | 343/343 | 342/343 | 342/343 | 343/343 | 341/343 | 340/340 | 335/340 | 331/335 |
| | 100.0% | 100.0% | 99.7% | 99.7% | 100.0% | 99.4% | 100.0% | 98.5% | 98.8% |
| *Discontinued includes subjects that were discontinued due to reasons other than lost to follow-up. Discontinued counts and Lost to follow-up (LTFU) counts are cumulative from the first visit interval onward to each respective column. **For Discontinued counts in Month 12 column, subjects who missed Month 12 visit and were subsequently exited after the visit window closed (3 withdrew consents) are included with the subjects who were exited cumulative through the Month 12 visit window (5 discontinued due to other reasons). †For LTFU counts, subjects were counted as lost to follow-up after the last visit at which they were seen, regardless of when they were subsequently exited. Note: The early study visits (Day 1, Week 1, Month 1) are presented by eye; the order of these visits listed for accountability does not necessarily represent the actual order of the visits. Accountability = Available for Analysis / (N - Discontinued - Active). Other percentages were calculated as (n / N) * 100%. | | | | | | | | | |

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Table 10. Control Group Subject Accountability (N=110) (n/N, %)

| | Day 1 (1st Eye) | Week 1 (1st Eye) | Month 1 (1st Eye) | Day 1 (2nd Eye) | Week 1 (2nd Eye) | Month 1 (2nd Eye) | Month 3 | Month 6 | Month 12 |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
| Active | 0/110
0.0% | 0/110
0.0% | 0/110
0.0% | 0/110
0.0% | 0/110
0.0% | 0/110
0.0% | 0/110
0.0% | 0/110
0.0% | 0/110
0.0% |
| Available for Analysis | 110/11
0
100.0% | 110/11
0
100.0% | 109/11
0
99.1% | 110/110
100.0% | 109/110
99.1% | 108/110
98.2% | 106/110
96.4% | 100/110
90.9% | 101/110
91.8% |
| Missing Subjects | 0/110
0.0% | 0/110
0.0% | 1/110
0.9% | 0/110
0.0% | 1/110
0.9% | 2/110
1.8% | 4/110
3.6% | 10/110
9.1% | 9/110
8.2% |
| Discontinued* | 0/110
0.0% | 0/110
0.0% | 1/110
0.9% | 0/110
0.0% | 0/110
0.0% | 1/110
0.9% | 1/110
0.9% | 3/110
2.7% | 4/110
3.6% |
| Lost to follow-up | 0/110
0.0% | 0/110
0.0% | 0/110
0.0% | 0/110
0.0% | 0/110
0.0% | 1/110
0.9%† | 3/110
2.7%† | 5/110
4.5%† | 5/110
4.5%† |
| Missed Visit | 0/110
0.0% | 0/110
0.0% | 0/110
0.0% | 0/110
0.0% | 1/110
0.9% | 0/110
0.0% | 0/110
0.0% | 2/110
1.8% | 0/110
0.0% |
| Accountability | 110/11
0
100.0% | 110/11
0
100.0% | 109/10
9
100.0% | 110/110
100.0% | 109/110
99.1% | 108/109
99.1% | 106/109
97.2% | 100/107
93.5% | 101/106
95.3% |
| *Discontinued includes subjects that were discontinued due to reasons other than lost to follow-up. Discontinued counts and Lost to follow-up (LTFU) counts are cumulative from the first visit interval onward to each respective column.
†For LTFU counts, subjects were counted as lost to follow-up after the last visit at which they were seen, regardless of when they were subsequently exited.
Note: The early study visits (Day 1, Week 1, Month 1) are presented by eye; the order of these visits listed for accountability does not necessarily represent the actual order of the visits.
Accountability = Available for Analysis / (N – Discontinued – Active). Other percentages were calculated as (n / N) * 100%. | | | | | | | | | |

## C. Study Population Demographics and Baseline Parameters

The demographics of the study population are typical for a prospective, non-randomized, multi-center, parallel-group clinical study of intraocular lenses performed in the US.

The study population demographics and baseline parameters measured from optical biometry are reported in Tables 11 and 12. The control group enrolled more subjects aged 80 years and older. Otherwise, the demographic and baseline characteristics were similar between the two groups.

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Table 11. Demographics

| Parameters | IC-8 Group (N=343) | | Control Group (N=110) | | Overall (N=453) | |
| --- | --- | --- | --- | --- | --- | --- |
| Age (years) | | | | | | |
| Mean (SD) | 66.1 (7.96) | | 69.1 (8.63) | | 66.8 (8.22) | |
| Median | 67.0 | | 70.0 | | 67.0 | |
| Q1, Q3 | 61.0, 71.0 | | 64.0, 75.0 | | 62.0, 72.0 | |
| Min, Max | 36, 85 | | 45, 90 | | 36, 90 | |
| 95% CI | 65.2, 66.9 | | 67.5, 70.8 | | 66.1, 67.6 | |
| Age Group (n/N, %) | | | | | | |
| < 60 | 70/343 | 20.4% | 12/110 | 10.9% | 82/453 | 18.1% |
| 60-69 | 152/343 | 44.3% | 42/110 | 38.2% | 194/453 | 42.8% |
| 70-79 | 108/343 | 31.5% | 42/110 | 38.2% | 150/453 | 33.1% |
| ≥ 80 | 13/343 | 3.8% | 14/110 | 12.7% | 27/453 | 6.0% |
| Sex (n/N, %) | | | | | | |
| Male | 132/343 | 38.5% | 34/110 | 30.9% | 166/453 | 36.6% |
| Female | 211/343 | 61.5% | 76/110 | 69.1% | 287/453 | 63.4% |
| Race (n/N, %) | | | | | | |
| American Indian/Alaska Native | 1/343 | 0.3% | 1/110 | 0.9% | 2/453 | 0.4% |
| Asian | 3/343 | 0.9% | 3/110 | 2.7% | 6/453 | 1.3% |
| Black/African American | 22/343 | 6.4% | 6/110 | 5.5% | 28/453 | 6.2% |
| White | 311/343 | 90.7% | 99/110 | 90.0% | 410/453 | 90.5% |
| Other | 6/343 | 1.7% | 1/110 | 0.9% | 7/453 | 1.5% |
| Ethnicity (n/N, %) | | | | | | |
| Hispanic/Latino | 22/343 | 6.4% | 10/110 | 9.1% | 32/453 | 7.1% |
| Not Hispanic/Latino | 320/343 | 93.3% | 100/110 | 90.9% | 420/453 | 92.7% |
| Unknown | 1/343 | 0.3% | 0/110 | 0.0% | 1/453 | 0.2% |
| Iris Color (n/N, %) | | | | | | |
| Blue | 105/343 | 30.6% | 43/110 | 39.1% | 148/453 | 32.7% |
| Brown | 153/343 | 44.6% | 49/110 | 44.5% | 202/453 | 44.6% |
| Gray | 1/343 | 0.3% | 0/110 | 0.0% | 1/453 | 0.2% |
| Green | 28/343 | 8.2% | 6/110 | 5.5% | 34/453 | 7.5% |
| Other | 56/343 | 6.3% | 12/110 | 10.9% | 68/453 | 15.0% |
| N = Total # in the Analysis population. n = # subjects with data in the respective category. % = n /N *100%. Abbreviations: Q1, Q3=First and third quartile; SD=Standard Deviation. IC-8 and Control Groups were compared with Fisher's exact tests for binary variables, Chi-square tests for categorical variables, and a t-test for continuous variables. | | | | | | |

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Table 12. Baseline Parameters

| Baseline Parameter | IC-8 Group | | Control Group | |
| --- | --- | --- | --- | --- |
| | IC-8 Eyes (N=343) | Fellow Eyes (N=343) | Second Eyes (N=110) | First Eyes (N=110) |
| Axial length (mm) | | | | |
| M | 343 | 343 | 110 | 110 |
| Mean (SD) | 23.780 (0.9440) | 23.789 (0.9535) | 23.921 (1.1265) | 23.892 (1.0960) |
| Median | 23.730 | 23.740 | 23.740 | 23.750 |
| Min, Max | 21.30, 26.56 | 21.30, 27.00 | 20.75, 27.10 | 20.78, 26.81 |
| 95% CI | 23.680, 23.880 | 23.688, 23.891 | 23.708, 24.134 | 23.685, 24.099 |
| Anterior chamber depth (mm) | | | | |
| M | 343 | 343 | 110 | 110 |
| Mean (SD) | 3.223 (0.3895) | 3.213 (0.3753) | 3.228 (0.4057) | 3.247 (0.4058) |
| Median | 3.200 | 3.190 | 3.220 | 3.275 |
| Min, Max | 2.09, 4.36 | 2.19, 4.34 | 1.94, 4.32 | 2.05, 4.41 |
| 95% CI | 3.182, 3.264 | 3.173, 3.253 | 3.151, 3.304 | 3.171, 3.324 |
| White to white (mm) | | | | |
| M | 343 | 343 | 110 | 110 |
| Mean (SD) | 12.071 (0.4480) | 12.073 (0.4443) | 12.024 (0.4107) | 12.059 (0.4245) |
| Median | 12.060 | 12.110 | 12.040 | 12.045 |
| Min, Max | 10.55, 13.23 | 10.46, 13.23 | 11.00, 13.02 | 11.10, 13.06 |
| 95% CI | 12.023, 12.119 | 12.026, 12.121 | 11.946, 12.102 | 11.978, 12.139 |
| Lens thickness (mm) | | | | |
| M | 333 | 333 | 109 | 110 |
| Mean (SD) | 4.499 (0.4213) | 4.527 (0.4346) | 4.501 (0.4253) | 4.462 (0.4289) |
| Median | 4.480 | 4.530 | 4.510 | 4.460 |
| Min, Max | 3.02, 5.86 | 2.97, 5.88 | 3.44, 5.79 | 3.44, 5.66 |
| 95% CI | 4.454, 4.544 | 4.480, 4.574 | 4.421, 4.582 | 4.381, 4.543 |
| Keratometric cylinder (D) | | | | |
| M | 343 | 343 | 110 | 110 |
| Mean (SD) | 0.648 (0.3698) | 0.655 (0.3761) | 0.665 (0.3541) | 0.636 (0.3725) |
| Median | 0.610 | 0.620 | 0.620 | 0.585 |
| Min, Max | 0.00, 1.50 | 0.00, 1.49 | 0.00, 1.50 | 0.00, 1.45 |
| 95% CI | 0.609, 0.687 | 0.615, 0.695 | 0.598, 0.732 | 0.565, 0.706 |
| N = Total # in the Analysis population. M = # subjects with available data for the respective parameter. | | | | |

Table 13 provides the mean intended target spherical equivalent refraction for the chosen IOL power implanted in the IDE clinical trial, showing -0.852 D mean target refraction for the IC-8 IOL and -0.112 to -0.146 D mean target refraction for monofocal or monofocal toric IOLs.

Manifest refraction was conducted using the duochrome technique in the study with a computerized test system (CTS, M&amp;S® Technologies, Niles, IL). Mean ± SD manifest spherical equivalent (MRSE) at 6 Months in the IC-8 IOL eyes was -0.314 ±0.4637, and -0.021 ±0.3815 in the second eyes of the Control group. In the first monofocal or monofocal toric eyes, mean ± SD MRSE was 0.073 ±0.3679 for the IC-8 IOL group and 0.003 ±0.3589 for the Control group subjects.

Table 14 shows the percentages of absolute MRSE by treatment groups compared to the intended target spherical equivalent manifest refraction at 6 Months.

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Table 13. Mean Intended Target Spherical Equivalent (for IOL Implantation)

| Target Spherical Equivalent (D) | IC-8 Group | | Control Group | |
| --- | --- | --- | --- | --- |
| | IC-8 Eyes (N=343) | Fellow Eyes (N=343) | Second Eyes (N=110) | First Eyes (N=110) |
| Mean (SD) | -0.852 (0.1351) | -0.112 (0.1553) | -0.146 (0.1296) | -0.145 (0.1309) |
| Median | -0.860 | -0.110 | -0.140 | -0.150 |
| Min, Max | -1.30, -0.20 | -0.62, 0.37 | -0.52, 0.16 | -0.51, 0.23 |
| 95% CI | -0.867, -0.838 | -0.129, -0.096 | -0.171, -0.122 | -0.169, -0.120 |

Table 14. Percentage of Absolute MRSE vs. Intended Target at 6 Months

| MRSE vs. Target | IC-8 Group | | Control Group | |
| --- | --- | --- | --- | --- |
| | IC-8 Eyes n/N (%) | Fellow Eyes n/N (%) | Second Eyes n/N (%) | First Eyes n/N (%) |
| ≤ 0.25 D | 62/334 (18.6%) | 162/334 (48.5%) | 47/100 (47.0%) | 46/100 (46.0%) |
| ≤ 0.50 D | 139/334 (41.6%) | 258/334 (77.2%) | 82/100 (82.0%) | 76/100 (76.0%) |
| ≤ 1.00 | 287/334 (85.9%) | 327/334 (97.9%) | 99/100 (99.0%) | 99/100 (99.0%) |
| > 1.00 D | 47/334 (14.1%) | 7/334 (2.1%) | 1/100 (1.0%) | 1/100 (1.0%) |

## D. Safety and Effectiveness Results

### 1. Safety Results

The analysis of safety was based on the safety cohort of 453 implanted subjects: 343 IC-8 IOL subjects and 110 control subjects, available for the 12-month evaluation. The key safety outcomes for this study are presented below in Tables 15 to 24. Adverse effects are reported in Tables 15 to 19.

The first co-primary safety objective was to evaluate monocular BCDVA in the IC-8 eyes at 12 Months. The second co-primary safety objective was to evaluate the rates of ocular adverse events (cumulative or persistent) through 12 Months compared to ISO 11979-7:2014 SPE rates for posterior chamber IOLs. The third co-primary safety objective was to evaluate the rate of IC-8 IOL removals due to visual/optical reasons, cumulative through 12 Months. The secondary safety objective was the assessment of contrast sensitivity at 6 Months. Additional safety analyses included monocular and binocular low contrast (10%) uncorrected distance, intermediate and near visual acuities in the test group and control group at 6 months (to be performed in the contrast sensitivity subgroup with BCDVA 20/25 or better in each eye). Other safety parameters included Patient Reported Outcomes (PRO) and non-directed question data, analyzed by descriptive statistics, as well as retinal diagnostic testing evaluations.

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# Adverse effects that occurred in the PMA clinical study:

The rate of cumulative and persistent ocular adverse events for IC-8 eyes were compared to the ISO 11979-7:2014 SPE rates (Table 15 and 16). The thresholds (95% LCL) for all the observed adverse event types in IC-8 eyes, except for the cumulative rate of secondary surgical interventions (SSIs), were statistically below the SPE rates. A description of the SSIs is provided in Tables 15. The 95% LCL rates for persistent adverse events were statistically below the SPE rates for all persistent serious adverse event (SAE) types observed in IC-8 eyes in the study (Table 16).

Table 15. Cumulative Ocular Serious Adverse Events in IC-8 IOL Eyes and Fellow Eyes through 12 Months (IC-8 IOL Group)

| Cumulative SAE | SPE Rate | IC-8 Eyes | | | | Fellow Eyes | | | |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
| | | (N=343) | | | | (N=343) | | | |
| | | n/N | % | 95% LCL | p-value | n/N | % | 95% LCL | p-value |
| Cystoid macular edema | 3.0% | 5/343 | 1.5% | 0.6% | 0.977 | 4/343 | 1.2% | 0.4% | 0.992 |
| Hypopyon | 0.3% | 0/343 | 0.0% | 0.0% | >0.999 | 0/343 | 0.0% | 0.0% | >0.999 |
| Endophthalmitis | 0.1% | 1/343 | 0.3% | 0.0% | 0.290 | 0/343 | 0.0% | 0.0% | >0.999 |
| Lens dislocated from posterior chamber | 0.1% | 0/343 | 0.0% | 0.0% | >0.999 | 0/343 | 0.0% | 0.0% | >0.999 |
| Pupillary block | 0.1% | 0/343 | 0.0% | 0.0% | >0.999 | 0/343 | 0.0% | 0.0% | >0.999 |
| Retinal detachment | 0.3% | 0/343 | 0.0% | 0.0% | >0.999 | 0/343 | 0.0% | 0.0% | >0.999 |
| Secondary surgical intervention‡ | 0.8% | 10/343 | 2.9% | 1.6% | <.001 | 6/343 | 1.7% | 0.8% | 0.060 |
| IOL repositioning | N/A | 1/343 | 0.3% | 0.0% | -- | 1/343 | 0.3% | 0.0% | -- |
| Removal of retained cortex | N/A | 2/343 | 0.6% | 0.1% | -- | 0/343 | 0.0% | 0.0% | -- |
| Vitrectomy | N/A | 4/343 | 1.2% | 0.4% | -- | 1/343 | 0.3% | 0.0% | -- |
| Modified paracentesis* | N/A | 4/343 | 1.2% | 0.4% | -- | 3/343 | 0.9% | 0.2% | -- |
| Intravitreal injection** | N/A | 1/343 | 0.3% | 0.0% | -- | 1/343 | 0.3% | 0.0% | -- |
| Laser retinopexy† | N/A | 0/343 | 0.0% | 0.0% | -- | 1/343 | 0.3% | 0.0% | -- |
| Other: Retinal vein occlusion | N/A | 1/331 | 0.3% | 0.0% | -- | 0/331 | 0.0% | 0.0% | -- |
| N = Total # in the Analysis population; n = # eyes with events in the respective AE category. The rate of adverse event is based on the proportion of eyes with events, % = (n / N) * 100. | | | | | | | | | |

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SPE = Safety and Performance Endpoints (SPE) rates per ISO 11979-7:2014 Table B.2 for posterior chamber IOL.

95% LCL = one-sided 95% lower confidence limit (based on exact binomial distribution). The SPE rate is considered not exceeded if the one-sided 95% lower CL for an AE is less than the SPE rate, equivalent to p-value greater than 0.05.

- Cystoid macular edema: Macular edema diagnosed by clinical examination and adjunct testing (e.g., OCT, FA) resulting in BCDVA of 20/40 or worse at 1 month or later.
- Endophthalmitis: Intraocular inflammation leading to diagnostic vitreous tap and intraocular antibiotics
- Any other AEs that were standard medical diagnoses were coded per MedDRA.

* Modified paracentesis procedure (also known as 'burping the wound') in the study were all performed in an exam room via the slit-lamp as an outpatient procedure to expel excess aqueous from the eye via the original incision (paracentesis) site to lower intraocular pressure. No procedure involved the creation of a new incision or disruption of the original incision site to release the aqueous. There were 6 modified paracentesis procedures in 4 IC-8 Eyes, with 3 procedures in 1 IC-8 Eye (which also had a removal of retained cortex). There were 3 modified paracentesis procedures in 3 Fellow Eyes.

** Intravitreal injection as treatment for cystoid macular edema.

† Laser retinopexy as treatment for operculated tear.

‡ No IC-8 IOL removals were reported during the study. In the Control group, one subject was reported with bilateral IOL removal during the study, and replacement of both of their monofocal IOLs with different monofocal lenses due to visual complaints of dysphotopsia. Following exit from the IDE study but prior to completion of the 12-months post-operative period, one subject previously enrolled in the Control group had their monofocal IOL removed in one eye due to visual complaints of double vision and a "yellow tint", and two subjects previously enrolled in the IC-8 IOL group had their IC-8 IOLs removed. One subject had their IC-8 IOL removed due to visual complaints of a "hinged blob". The Investigator believed that the cause may be one of three things: 1) Posterior Vitreous Detachment (PVD) or Vitreous consolidation, 2) A remnant of capsule in the subject's visual axis, 3) The YAG laser capsulotomy resulted in a "spot" (direct quote from Investigator) on the inner portion of the aperture resulting in a "little refractive spot change" (direct quote from Investigator). The other subject had their IC-8 IOL removed due to subjective complaints of starburst, glare, and halo.

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Table 16. Persistent Ocular Serious Adverse Events in IC-8 IOL Eyes and Fellow Eyes through 12 Months (IC-8 IOL Group)

| Persistent SAE | SPE Rate | IC-8 Eyes | | | | Fellow Eyes | | | |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
| | | n/N | % | 95% LCL | p-value | n/N | % | 95% LCL | p-value |
| Corneal stromal edema | 0.3% | 0/331 | 0.0% | 0.0% | >0.999 | 0/331 | 0.0% | 0.0% | >0.999 |
| Cystoid macular edema | 0.5% | 1/331 | 0.3% | 0.0% | 0.810 | 1/331 | 0.3% | 0.0% | 0.810 |
| Iritis | 0.3% | 2/331 | 0.6% | 0.1% | 0.262 | 1/331 | 0.3% | 0.0% | 0.630 |
| Raised IOP requiring treatment | 0.4% | 0/331 | 0.0% | 0.0% | >0.999 | 0/331 | 0.0% | 0.0% | >0.999 |
| Other: Retinal vein occlusion | N/A | 1/331 | 0.3% | 0.0% | -- | 0/331 | 0.0% | 0.0% | -- |
| N = # eyes available at 12 Months; n = # eyes with events in the respective AE category. The rate of adverse event is based on the proportion of eyes with events, % = (n / N) * 100. SPE = Safety and Performance Endpoints (SPE) rates per ISO 11979-7:2014 Table B.2 for posterior chamber IOL. 95% LCL = one-sided 95% lower confidence limit (based on exact binomial distribution). The SPE rate is considered not exceeded if the one-sided 95% lower CL for an AE is less than the SPE rate, equivalent to p-value greater than 0.05. - Corneal stromal edema: Corneal swelling (stromal) resulting in BCDVA of 20/40 or worse at 1 month or later. - Cystoid macular edema: Macular edema diagnosed by clinical examination and adjunct testing (e.g., OCT, FA) resulting in BCDVA of 20/40 or worse at 1 month or later. - Raised IOP requiring treatment: Elevation of IOP greater than or equal to 10 mmHg above baseline to a minimum of 25mmHg. - Any other AEs that were standard medical diagnoses were coded per MedDRA. | | | | | | | | | |

As presented in Table 17, two of the pars plana vitrectomies in IC-8 eyes were performed to remove posterior capsular remnants that were causing visual disturbances following YAG laser capsulotomies. One vitrectomy was performed in an IC-8 eye to treat visually significant floaters that were also present preoperatively; a vitrectomy was also performed in the fellow eye of this subject (implanted with a control IOL) to treat visually significant floaters that were present preoperatively. One vitrectomy was a modified vitrectomy concurrent with intravitreal injection performed to treat a case of endophthalmitis.

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Table 17. Postoperative Ocular Adverse Events through 12 Months: Secondary Surgical Interventions

| SSI | IC-8 Group | | | | Control Group | | | |
| --- | --- | --- | --- | --- | --- | --- | --- | --- |
| | IC-8 Eyes | | Fellow Eyes | | Second Eyes | | First Eyes | |
| | (N=343) | | (N=343) | | (N=110) | | (N=110) | |
| | n/N (%) | | n/N (%) | | n/N (%) | | n/N (%) | |
| | 90% CI | | 90% CI | | 90% CI | | 90% CI | |
| Intravitreal injection | 1/343 | (0.3%) | 1/343 | (0.3%) | 0/110 | (0.0%) | 1/110 | (0.9%) |
| | 0.0%, 1.4% | | 0.0%, 1.4% | | 0.0%, 2.7% | | 0.0%, 4.2% | |
| IOL exchange* | 0/343 | (0.0%) | 0/343 | (0.0%) | 1/110 | (0.9%) | 1/110 | (0.9%) |
| | 0.0%, 0.9% | | 0.0%, 0.9% | | 0.0%, 4.2% | | 0.0%, 4.2% | |
| IOL repositioning | 1/343 | (0.3%) | 1/343 | (0.3%) | 0/110 | (0.0%) | 1/110 | (0.9%) |
| | 0.0%, 1.4% | | 0.0%, 1.4% | | 0.0%, 2.7% | | 0.0%, 4.2% | |
| Iris reposition | 0/343 | (0.0%) | 0/343 | (0.0%) | 0/110 | (0.0%) | 1/110 | (0.9%) |
| | 0.0%, 0.9% | | 0.0%, 0.9% | | 0.0%, 2.7% | | 0.0%, 4.2% | |
| Laser retinopexy | 0/343 | (0.0%) | 1/343 | (0.3%) | 0/110 | (0.0%) | 0/110 | (0.0%) |
| | 0.0%, 0.9% | | 0.0%, 1.4% | | 0.0%, 2.7% | | 0.0%, 2.7% | |
| Laser Vitreolysis | 0/343 | (0.0%) | 0/343 | (0.0%) | 1/110 | (0.9%) | 0/110 | (0.0%) |
| | 0.0%, 0.9% | | 0.0%, 0.9% | | 0.0%, 4.2% | | 0.0%, 2.7% | |
| Modified paracentesis** | 4/343 | (1.2%) | 3/343 | (0.9%) | 0/110 | (0.0%) | 1/110 | (0.9%) |
| | 0.4%, 2.6% | | 0.2%, 2.2% | | 0.0%, 2.7% | | 0.0%, 4.2% | |
| Removal of retained cortex | 2/343 | (0.6%) | 0/343 | (0.0%) | 0/110 | (0.0%) | 0/110 | (0.0%) |
| | 0.1%, 1.8% | | 0.0%, 0.9% | | 0.0%, 2.7% | | 0.0%, 2.7% | |
| Vitrectomy | 4/343 | (1.2%) | 1/343 | (0.3%) | 0/110 | (0.0%) | 0/110 | (0.0%) |
| | 0.4%, 2.6% | | 0.0%, 1.4% | | 0.0%, 2.7% | | 0.0%, 2.7% | |
| - to remove posterior capsular remnant | 2/343 | (0.6%) | 0/343 | (0.0%) | 0/110 | (0.0%) | 0/110 | (0.0%) |
| | 0.1%, 1.8% | | 0.0%, 0.9% | | 0.0%, 2.7% | | 0.0%, 2.7% | |
| - to treat endophthalmitis | 1/343 | (0.3%) | 0/343 | (0.0%) | 0/110 | (0.0%) | 0/110 | (0.0%) |
| | 0.0%, 1.4% | | 0.0%, 0.9% | | 0.0%, 2.7% | | 0.0%, 2.7% | |
| - to remove bilateral vitreous floaters | 1/343 | (0.3%) | 1/343 | (0.3%) | 0/110 | (0.0%) | 0/110 | (0.0%) |
| | 0.0%, 1.4% | | 0.0%, 1.4% | | 0.0%, 2.7% | | 0.0%, 2.7% | |
| N = Total # in the Analysis population; n = # eyes with events in the respective AE category.The rate of adverse event is based on the proportion of eyes with events, % = (n / N) * 100.90% CI = two-sided 90% confidence interval (based on exact binomial distribution).*No IC-8 IOL removals were reported during the study. Two subjects had their IC-8 IOLs removed after study exit, but within 12 months post-implantation. In the Control group, one subject was reported with bilateral IOL removal during the study, and replacement of both of their monofocal IOLs with different monofocal lenses. Following exit from the IDE study, one subject previously enrolled in the Control group had their monofocal IOL | | | | | | | | |

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removed in one eye. All subjects requested removals due to subjective reports of visual symptoms.

**Modified paracentesis procedure (also known as 'burping the wound') in the study were all performed in an exam room via the slit-lamp as an outpatient procedure to expel excess aqueous from the eye via the original incision (paracentesis) site to lower intraocular pressure. No procedure involved the creation of a new incision or disruption of the original incision site to release the aqueous. There was 1 eye/subject (IC-8 eye in a Test Group subject) with 3 modified paracentesis procedures in the same eye; other eyes/subjects had 1 paracentesis procedure each.

There were no removals of the IC-8 IOL reported during the study, yielding a rate of $0\%$ (0/343) with $95\%$ upper confidence limit (UCL) of $0.9\%$ (below the criterion of $3.1\%$ ), which claimed the statistical success for this endpoint (Table 18). Following study exit, but prior to completing the 12-month post-operative period, two subjects had their IC-8 devices removed. One subject had their IC-8 device removed due to complaints of a "hinged blob." The Investigator believed that the cause may be one of three things: 1) Posterior vitreous detachment (PVD) or vitreous consolidation, 2) A remnant of capsule in the subject's visual axis, 3) The YAG capsulotomy resulted in a "spot" on inner portion of the aperture resulting in a "little refractive spot change". The other subject had their IC-8 device removed due to subjective complaints of starburst, glare, and halo.

In the Control group, one subject was reported with bilateral IOL removal during the study, and replacement of both of their monofocal IOLs with different monofocal lenses. Following exit from the IDE study, one subject previously enrolled in the Control group had their control device removed in one eye. All subjects requested removals due to subjective reports of visual symptoms.

Table 18. IOL Removals in the IC-8 IOL Group and Control Group through 12 Months

| | IC-8 IOL Group | | | | Control Group | | | |
| --- | --- | --- | --- | --- | --- | --- | --- | --- |
| | IC-8 IOL Eyes | | Fellow Eyes | | Second Eyes | | First Eyes | |
| | n/N | % | n/M | % | n/M | % | n/M | % |
| IOL Removals Total | 0/343 | 0.0% | 0/343 | 0.0% | 1/110 | 0.9% | 1/110 | 0.9% |
| Due to Visual/Optical Reasons* | 0/343 | 0.0% | 0/343 | 0.0% | 1/110 | 0.9% | 1/110 | 0.9% |
| Due to Other Reasons | 0/343 | 0.0% | 0/343 | 0.0% | 0/110 | 0.0% | 0/110 | 0.0% |
| N = Total # in the Analysis population; n = # eyes with events in the respective AE category. The rate of adverse events is based on the proportion of eyes with events, % = (n / M) * 100. 95% UCL = one-sided 95% upper confidence limit (based on exact binomial distribution). The one-sided 95% upper CL of IC-8 IOL removal rate due to visual/optical reasons less than 3.1% claimed statistical success. *Following exit from the IDE study but prior to completion of the 12-months post-operative period, two subjects previously enrolled in the IC-8 IOL group had their IC-8 IOLs removed, and one subject previously enrolled in the Control group had their monofocal IOL removed in one eye, due to visual/optical reasons. | | | | | | | | |

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Supportive characterization of ocular adverse events, based on a modified version of the American Academy of Ophthalmology Task Force Consensus Statement on Adverse Events with Intraocular Lenses (Masket et al., 2017) are presented in Table 19.

There were five surgical complications and/or intraoperative AEs reported during the study, all in IC-8 eyes of the Test Group (5/343, 1.5%); two detached Descemet's Membrane events, one corneal abrasion event, one surgical complication (and a device deficiency) of missing IOL haptic (back up IC-8 IOL implanted with no complication), and one surgical complication of zonular dehiscence. There was one device deficiency of ophthalmic viscosurgical device (OVD) hardening in the IOL injector (back up IC-8 IOL implanted with no complication).

Table 19. Ocular Adverse Events Based on a Modified Version of AAO Consensus (Masket et al., 2017) through 12 Months

| Cumulative AE | IC-8 IOL Group | | Control Group | |
| --- | --- | --- | --- | --- |
| | IC-8 IOL Eyes | Fellow Eyes | Second Eyes | First Eyes |
| | n/N (%) | n/N (%) | n/N (%) | n/N (%) |
| | 90% CI | 90% CI | 90% CI | 90% CI |
| Chronic anterior uveitis | 1/343 (0.3%) | 0/343 (0.0%) | 0/110 (0.0%) | 0/110 (0.0%) |
| | 0.0%, 1.4% | 0.0%, 0.9% | 0.0%, 2.7% | 0.0%, 2.7% |
| Clinically significant cystoid macular edema | 2/343 (0.6%) | 0/343 (0.0%) | 0/110 (0.0%) | 1/110 (0.9%) |
| | 0.1%, 1.8% | 0.0%, 0.9% | 0.0%, 2.7% | 0.0%, 4.2% |
| Visually significant corneal edema | 1/343 (0.3%) | 1/343 (0.3%) | 0/110 (0.0%) | 0/110 (0.0%) |
| | 0.0%, 1.4% | 0.0%, 1.4% | 0.0%, 2.7% | 0.0%, 2.7% |
| Endophthalmitis | 1/343 (0.3%) | 0/343 (0.0%) | 0/110 (0.0%) | 0/110 (0.0%) |
| | 0.0%, 1.4% | 0.0%, 0.9% | 0.0%, 2.7% | 0.0%, 2.7% |
| Mechanical pupillary block | 0/343 (0.0%) | 0/343 (0.0%) | 0/110 (0.0%) | 0/110 (0.0%) |
| | 0.0%, 0.9% | 0.0%, 0.9% | 0.0%, 2.7% | 0.0%, 2.7% |
| Intraocular pressure increased | 20/343 (5.8%) | 16/343 (4.7%) | 10/110 (9.1%) | 7/110 (6.4%) |
| | 3.9%, 8.4% | 2.9%, 7.0% | 5.0%, 14.9% | 3.0%, 11.6% |
| Rhegmatogenous RD | 0/343 (0.0%) | 0/343 (0.0%) | 0/110 (0.0%) | 0/110 (0.0%) |
| | 0.0%, 0.9% | 0.0%, 0.9% | 0.0%, 2.7% | 0.0%, 2.7% |
| Toxic anterior segment syndrome (TASS) | 0/343 (0.0%) | 0/343 (0.0%) | 0/110 (0.0%) | 0/110 (0.0%) |
| | 0.0%, 0.9% | 0.0%, 0.9% | 0.0%, 2.7% | 0.0%, 2.7% |
| Secondary IOL intervention* | | | | |
| IOL exchange | 0/343 (0.0%) | 0/343 (0.0%) | 1/110 (0.9%) | 1/110 (0.9%) |
| | 0.0%, 0.9% | 0.0%, 0.9% | 0.0%, 4.2% | 0.0%, 4.2% |
| IOL removal | 0/343 (0.0%) | 0/343 (0.0%) | 0/110 (0.0%) | 0/110 (0.0%) |
| | 0.0%, 0.9% | 0.0%, 0.9% | 0.0%, 2.7% | 0.0%, 2.7% |

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| IOL reposition | 1/343 (0.3%) | 1/343 (0.3%) | 0/110 (0.0%) | 1/110 (0.9%) |
| --- | --- | --- | --- | --- |
| | 0.0%, 1.4% | 0.0%, 1.4% | 0.0%, 2.7% | 0.0%, 4.2% |
| N = Total # in the Analysis population; n = # subjects with events in the respective AE category. The rate of adverse event is based on the proportion of eyes with events, % = (n / N) * 100. 90% CI = two-sided 90% confidence interval (based on exact binomial distribution). - Chronic anterior uveitis: Anterior segment inflammation characterized by grade 1+ cell or greater using Standardization of Uveitis Nomenclature (SUN) criteria that persists for greater than 3 months after surgery, or relapses in less than 3 months after discontinuation of therapy, or the subject is maintained on therapy for more than 3 months to control inflammation. - Clinically significant cystoid macular edema: Macular edema diagnosed by clinical examination and adjunct testing(e.g., OCT, FA) resulting in BCDVA of <=20/40 at >=1 month. - (Visually significant) corneal edema: Corneal swelling (stromal or epithelial) resulting in BCDVA of <=20/40 at >=1 month. - Endophthalmitis: Intraocular inflammation leading to diagnostic vitreous tap and intraocular antibiotics - Mechanical pupillary block: Shallowing of anterior chamber due to obstruction of aqueous humor flow from the posterior to anterior chamber through the pupil by the crystalline lens, vitreous face, or implanted device. - Intraocular pressure increased (Increased IOP): Elevation of IOP by >=10 mmHg above baseline to a minimum of 25 mmHg. - Rhegmatogenous RD: Partial or complete RD associated with retinal tear. - Toxic anterior segment syndrome (TASS): Acute, non-infectious inflammation of the anterior segment that starts within 24 to 48 hours after surgery, usually resulting in hypopyon and commonly presenting with corneal edema, and that improves with steroid treatment. - IOL Exchange: The investigational device is replaced with the same lens model. - IOL Removal: The investigational device is removed and replaced with a non-investigational lens or no lens is implanted. - IOL Reposition: The existing IOL is surgically moved to another location or rotated. * No IC-8 IOL removals were reported during the study. In the Control group, one subject was reported with bilateral IOL removal during the study, and replacement of both of their monofocal IOLs with different monofocal lenses due to visual complaints of dysphotopsia. Following exit from the IDE study but prior to completion of the 12-months post-operative period, one subject previously enrolled in the Control group had their monofocal IOL removed in one eye due to visual complaints of double vision and a “yellow tint”, and two subjects previously enrolled in the IC-8 IOL group had their IC-8 IOLs removed. One subject had their IC-8 IOL removed due to visual complaints of a “hinged blob”. The Investigator believed that the cause may be one of three things: 1) Posterior Vitreous Detachment (PVD) or Vitreous consolidation, 2) A remnant of capsule in the subject’s visual axis, 3) The YAG laser capsulotomy resulted in a “spot” (direct quote from Investigator) on the inner portion of the aperture resulting in a “little refractive spot change” (direct quote from Investigator). The other subject had their IC-8 IOL removed due to subjective complaints of starburst, glare, and halo. | | | | |

PMA P210005: FDA Summary of Safety and Effectiveness Data

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# Posterior Capsular Opacity (PCO) and Nd:YAG Laser treatments

The rate of clinically significant PCO was 32.4% (111/343) in IC-8 eyes compared with 14.0% to 17.3% (48/343 to 19/110) in the eyes with monofocal or monofocal toric IOLs. During the 12-month study, 31.2% (107 of 343) of IC-8 eyes received Nd:YAG laser posterior capsulotomies as treatment for PCO affecting vision. In 12.1% (13 of 107) of these capsulotomy procedures, the Investigators reported some difficulty in performing the procedure. A correlation between reporting some difficulty performing a capsulotomy procedure and reports of resultant issues or laser damage to the IOL was noted. In 15.9% (17 of 107) of these YAG procedures, 5 eyes required a second capsulotomy treatment (1 IC-8 device was damaged by the YAG laser in this group); 2 eyes required pars plana vitrectomy (PPV) to remove a residual posterior capsular remnant (1 IC-8 device in this group also had YAG laser damage); and another 10 eyes had pits or damage on the device due to the YAG laser treatment. Of the 11 subjects with reported YAG laser damage at the final study visit, 1 reported severe glare, 1 reported severe halo, and 1 reported severe starburst at 12 Months. Exploratory analyses of patient-reported outcomes for subjects with damaged IC-8 devices suggested increased rates of severity and bothersomeness of several subjective visual disturbances compared to subjects with non-damaged IC-8 devices. However, the majority of subjects who required additional surgical interventions due to YAG laser treatment difficulties achieved satisfactory visual outcomes.

# Monocular Best Corrected Distance Visual Acuity

Non-inferiority of the IC-8 eyes to the fellow eyes in the IC-8 group in monocular BCDVA was demonstrated based on a mean difference of 0.068 logMAR, with 95% UCL of 0.082 logMAR (less than the non-inferiority margin of 0.1 logMAR [p&lt;0.0001]) as presented in Table 20.

Table 20. Mean logMAR Monocular Best-corrected Distance Visual Acuity, 12 Months (IC-8 IOL Group)

| BCDVA | IC-8 Group | |
| --- | --- | --- |
| | IC-8 Eyes (N=343) | Fellow Eyes (N=343) |
| M | 331 | 331 |
| Mean (SD) | 0.009 (0.1131) | -0.059 (0.0928) |
| Snellen equiv. of Mean | 20/20 | 20/17 |
| Mean Differencea | 0.068 | -- |
| Mean Difference in Lines | 0.7 | -- |
| p-valueb | <…