Clinical Trial of a Hydrophilic EMV Toric Lens RAO210T in the Correction of Aphakia and Corneal Astigmatism

Clinical Trial to Investigate the Safety and Effectiveness of a Hydrophilic EMV Toric Lens RAO210T in the Correction of Aphakia and Post-operative Corneal Astigmatism

The objectives of the clinical investigation are to determine the safety and performance of the RayOne EMV Toric (Model RAO210T) following unilateral implantation and approximately 6 months (120 to 180 days) of post-operative assessment, as a randomized comparison to aspheric monofocal control for low cylinder (1.50 D). This patient population with cataracts and low corneal cylinder (+1.00 to +1.50 D) will have the natural crystalline lens removed and replaced with an intraocular lens in the capsular bag.

This study is a prospective, multicenter, randomized, active controlled, masked (assessor and subject) pivotal investigation for unilateral implantation of low cylinder (1.50 D) toric IOL. It compares the Rayner RAO210T toric IOL to the Rayner RAO600C aspheric monofocal IOL. Subjects who sign the ICF are considered enrolled in the study. After signing the ICF, subjects will be screened for eligibility. Inclusion and Exclusion Criteria must be applied prior to subject randomization. Subjects who meet all protocol-specified eligibility criteria will be assigned to the randomized controlled study arms if the study eye's estimated IOL cylinder power using Barrett Toric Calculator is 1.50 D. Randomized subjects receive either the Rayner RAO210T Toric IOL (1.50 D low cylinder) or the Rayner RAO600C aspheric monofocal IOL in the study eye.

Up to 295 adult subjects will be enrolled (consented) assuming a 15% screen failure rate, then up to 250 subjects will be randomized, of which approximately 125 subjects will be randomized to receive low cylinder (1.50 D) RayOne EMV Toric (Model RAO210T) in one eye and approximately 125 subjects randomized to receive the RAO600C aspheric monofocal IOL in one eye, to complete 120-180 days follow-up for at least 100 subjects in each group.

All subjects who meet inclusion criteria will be assigned to the randomized controlled study arms to receive either the RAO210T toric IOL (1.50 D low cylinder) or the RAO600C aspheric monofocal IOL in the study eye according to a 1:1 ratio. Randomization will be stratified by site.

Up to 11 U.S. sites will be encouraged to enroll a minimum of 20 subjects. No site will enroll more than 25% of the subjects enrolled in the study.

If a subject has significant cataract in both eyes, it is recommended that cataract surgery is performed in one eye before the subject is enrolled in the study. Once a subject has been enrolled, it is recommended that the fellow eye does not undergo cataract surgery (except for a YAG capsulotomy) throughout the duration of the study. At screening, if both eyes qualify for the study, the eye to undergo cataract surgery and IOL implantation is the eye with worse pre-operative BCDVA. If pre-operative BCDVA is the same for each eye, the right eye will be the study eye.

Subjects will complete 6 study visits in approximately 9 months. Subject participation is calculated as the difference between the time of the pre-operative visit to completion of Visit 4 (120 to 180 days post-operative).

Standard clinical trial methods will be used to minimize bias, such as the use of site personnel performing manifest refraction and visual acuity assessments masked to subject treatment assignment, masking of subjects in the randomized controlled investigation evaluating low cylinder power, standardized test procedures, common Investigator training and common inclusion and exclusion criteria.

In order to minimize bias, measures will be taken to mask the site personnel performing post-operative manifest refraction and visual acuity assessments, as to the subject's treatment assignment until after the final database lock. Every attempt should be made to have the same masked site personnel perform the same masked post-operative assessments for an individual subject throughout the subject's study participation.

Subjects will be masked to their IOL assignment in the randomized controlled investigation evaluating low cylinder power. All material which may indicate the subjects' assignment, e.g., packaging, documents, etc., will be removed from any areas where subjects and/or masked site personnel may see them. Unmasked personnel will further be instructed to scrupulously avoid conversation and communication with masked personnel, subjects and all other persons regarding subjects' assignments, outcomes, clinical courses, and all other information potentially relevant to the study and its conduct.

Study Groups:

• Toric (test) group - all subjects randomized to be implanted with the low cylinder (1.50 D) RayOne EMV Toric IOL (Model RAO210T)
• Monofocal (control) group - all subjects randomized to be implanted with the RAO600C Monofocal IOL

Sample Size Determination:

Subjects will be enrolled with the goal of completing a total of 200 subjects through Visit 4 within the randomized groups, of whom 100 were implanted with the low cylinder RayOne EMV Toric IOL (Model RAO210T) and 100 were implanted with the RAO600C monofocal IOL.

Effectiveness For effectiveness, 100 subjects (eyes) randomized to the Toric (test) group (lowest cylinder power +1.50D) and 100 subjects (eyes) randomized to the Monofocal (control) group completing Visit 4 yields over 98% statistical power to reject H0e in favor of H1e and conclude the Toric IOL has statistically significantly lower mean residual manifest cylinder at Visit 4 compared to the Monofocal IOL, using a one-sided t-test with an alpha level of 0.025 and assuming a true mean difference of 0.4 D and a standard deviation of 0.7 D in both groups.

Safety For safety, ISO 11979-7 and ANSI Z80.30 specifies that a minimum of 100 subjects should complete a clinical evaluation of an IOL, where a parent IOL has been approved, to obtain appropriate specificity around adverse event and visual acuity rates.

Handling of Missing Data:

Missing data will be imputed for selected endpoints using the methods specified under the analysis descriptions for the endpoints. Where possible, multiple imputation will be used. Except where mentioned in Section 7, missing data will not be imputed.

Multiplicity Considerations:

The overall type I error rate for the toric effectiveness analyses will be controlled at 0.05. The study will be considered successful if all of the primary effectiveness and safety endpoints are met. Thus, no adjustments for multiplicity are necessary.

All primary effectiveness and primary safety endpoints as described below are required to achieve successful outcomes in order to demonstrate study success.

Inclusion Criteria:

1. Male or female, 22 years or older at the pre-operative visit who have cataract with best corrected distance visual acuity of 0.30 logMAR (20/40) or worse in at least one eye with or without a glare source present who are eligible for phacoemulsification cataract surgery

2. Subjects who are projected to have best corrected distance visual acuity 0.20 logMAR (20/30) or better after IOL implantation by potential acuity meter (PAM) or Investigator estimation

3. Clear intraocular media other than cataract

4. Contact lens wearers must demonstrate stability of biometry

5. Have the capability to understand and sign an IRB approved informed consent form and privacy authorization in accordance with local regulations

6. Female subjects must be 1-year postmenopausal, surgically sterilized, or, if of childbearing potential, have a negative urine pregnancy test at the Pre-operative Visit. Women of childbearing potential must use an acceptable form of contraception throughout the study.

   Acceptable methods include at least one of the following: intrauterine (intrauterine device), hormonal (oral, injection, patch, implant, ring), barrier with spermicide (condom, diaphragm), or abstinence.

7. Have Investigator selected IOL spherical equivalent power between +10.0 D to +25.0 D in 0.5 D steps and IOL cylinder power of +1.50 D

8. Have pre-existing corneal astigmatism of 1.00 D to 1.50 D as determined by keratometry

9. Dilated pupil size 5.5 mm or greater to allow visualization of the toric IOL axis markings post-operatively

Exclusion Criteria:

1. Previous intraocular, corneal, or retinal detachment surgery, including corneal transplant, LASIK / LASEK / PRK, SMILE, astigmatic keratotomy and limbal relaxing incisions in the planned operative eye.
2. Diagnosed degenerative visual disorders (e.g. macular degeneration, retinal detachment, proliferative diabetic retinopathy, or other retinal disorders) that are predicted to cause future acuity losses to a level of 0.20 logMAR (20/30) or worse
3. Significant anterior segment pathology that might increase intraoperative risk or compromise IOL stability (e.g. pseudoexfoliation syndrome, any iris pathology)
4. Subjects with conditions associated with increased risk of zonular rupture (that may affect post-operative centration or tilt of IOL) in the planned operative eye
5. Potentially occludable angle or ciliary body tumor, or other pathology that might increase risk to subject safety, based on gonioscopic observation
6. Subjects reasonably expected to require secondary ocular surgical intervention or laser treatment (other than YAG capsulotomy)
7. Subjects with clinically significant corneal pathology, potentially affecting corneal topography
8. Subjects with traumatic cataract in the planned operative eye
9. Participating in a concurrent drug or device clinical trial or who have participated in a drug or device trial within 30 days of the pre-operative visit
10. Subjects with any other serious ocular pathology (e.g. glaucoma, severe dry eye, history of intraocular inflammation, history of retinal surgery or retinal laser procedure) or underlying systemic medical condition (e.g., uncontrolled diabetes) or circumstance that, based on the Investigator's judgment, poses a concern for the subjects' safety or could confound the results of the study (History of cataract surgery with PC-IOL in one eye is allowed.)
11. Use of medications known to interfere with visual performance, pupil dilation, or iris structure within 30 days of the pre-operative visit, at the discretion of the Investigator
12. Pregnant or nursing females
13. Irregular astigmatism in the planned operative eye