Efficacy and Safety of CLEAR in Myopia and Astigmatism in Chinese Population

A Multicentre, Prospective, Single-arm Clinical Trial to Evaluate Efficacy and Safety of Femtosecond Laser Corneal Lenticule Extraction for Advanced Refractive Correction (CLEAR) in Myopia and Astigmatism in Chinese Population

In this multicenter, prospective, interventional, single-arm clinical trial, the aim is to determine safety and efficacy of CLEAR using the FEMTO LDV Z8 in Chinese patients in China.

The primary objective is to evaluate the visual outcome after CLEAR using the FEMTO LDV Z8 in myopia and astigmatic myopia at the time point, when stability of manifest refraction spherical equivalent (MRSE) is reached.

The corresponding hypothesis is that the percentage of treated eyes with satisfactory Uncorrected Distance Visual Acuity (UCDVA) at the point when stability of MRSE is reached after CLEAR is at least 85% of all treated eyes. This hypothesis has been chosen in line with the recommendations of the "Checklist of Information Usually Submitted in an Investigational Device Exemptions (IDE) Application for Refractive Surgery Lasers" issued by the FDA.

The secondary objectives are to evaluate the efficacy and safety with respect to stability, predictability, device defects and adverse events of CLEAR using the FEMTO LDV Z8 in myopia and astigmatic myopia during follow-up.

Study Overview

• Status: Recruiting
• Conditions: Myopic Astigmatism
• Intervention / Treatment: Device: CLEAR

• Study Type: Interventional
• Enrollment (Anticipated): 215
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Olga Grossenbacher, MD, PhD; Phone Number: +41 79 671 67 25; Email: olga.grossenbacher@ziemergroup.com

Study Locations

• China
  • Bei-jing
    • Beijing, Bei-jing, China
      • Not yet recruiting
      • Beijing Tongren Hospital
      • Contact: Changbin Zhai, MD; Phone Number: 136 0108 9269
      • Principal Investigator: Changbin Zhai, MD
  • Guangdong
    • Guangzhou, Guangdong, China
      • Not yet recruiting
      • Guangzhou Aier Eye Hospital
      • Contact: Zheng Wang, MD; Phone Number: 139 0300 2594
      • Principal Investigator: Zheng Wang, MD
  • Sichuan
    • Chengdu, Sichuan, China
      • Not yet recruiting
      • Ineye Hospital of Chengdu University of TCM
      • Contact: Yuehua Zhou, MD; Phone Number: 139 1083 6019
      • Principal Investigator: Yuehua Zhou, MD
  • Zhejiang
    • Wenzhou, Zhejiang, China
      • Recruiting
      • Eye Hospital, WMU
      • Contact: Shi-hao Chen, MD; Phone Number: 139 6887 8892
      • Principal Investigator: Shi-hao Chen, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Medically suitable for corneal refractive surgery
2. Signed informed consent form
3. Age ≥ 18 years
4. Pre-operative BCVA ≥ 5.0 (corresponding to 20/20 as per Snellen chart lines)
5. Myopia sphere from -0.5 D to -10.00 D
6. Maximum cylinder diopter of -5.00 D
7. Maximum resulting MRSE of -12.5 D
8. Calculated residual stromal thickness ≥ 250 microns
9. Non-contact IOP < 21mmHg
10. Stable refraction for the past year, as demonstrated by a change in manifest refraction spherical equivalent (MRSE) of ≤ 0.50 D
11. A difference between cycloplegic refraction spherical equivalent and MRSE < 0.75 D.
12. For contact lens wearers (where applicable) after pre-operative stop of contact lens wear: Stable refraction (within ±0.5 D), as determined by MRSE, on two consecutive examinations at least 1 week apart.
13. Patient willing and able to return to the study site for the follow-up visits, in the judgement of the investigator.

Exclusion Criteria:

1. Wearing of contact lenses pre-operatively i) soft contact lenses: <2 weeks before Visit 1 OR from Visit 1 till the day of surgery ii) hard contact lenses: <1 month before Visit 1 OR from Visit 1 till the day of surgery iii) therapeutic contact lenses (such as Ortho-K): <3 months before Visit 1 OR from Visit 1 till the day of surgery
2. Corneal disease or pathology, such as corneal scaring or opacity, that precludes transmission of laser wavelength or that distorts laser light
3. Residual, recurrent, or active ocular disease or corneal abnormality (including, but not limited to ocular herpes zoster or simplex, active infections and inflammation)
4. History of ocular herpes simplex or herpes zoster keratitis
5. 3 months before the inclusion have taken systemic medication likely to negatively affect wound healing, such as glucocorticosteroide or antimetabolites
6. Severe dry eye
7. Glaucoma
8. Nystagmus or hemofacial spasm preventing placement of the patient interface
9. Previous corneal surgery of any kind, including any type of surgery for either refractive or therapeutic purposes
10. Unstable central keratometry readings
11. Mesopic pupil diameter > 8.0 mm
12. Keratometry readings via Sim-K values less than 40.00 D
13. Allergy to medications required in surgery, pre- and post-operative treatment
14. Keratoconus or keratectasia, including patients with suspicion of keratoconus on corneal topography
15. At the time of inclusion, participation in other medical device clinical trials within one month or in drug clinical trials within 3 months
16. Diagnosis of autoimmune disease, connective tissue disease, clinically significant atopic disease, diabetes or AIDS and other acute or chronic illnesses that increases the risk to the subject or confounds the outcomes of this study in the opinion of the study principal investigator
17. Known psychotic disorders associated with delusions (e.g. schizophrenia)
18. Woman who is pregnant or nursing

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

EXPERIMENTAL: Refractive correction using CLEAR; Subjects 18+ years old with myopic (-0.50 to -10.00 D) astigmatism (up to -5.00 D) treated bilaterally with FEMTO LDV Z8 using CLEAR application.

Device: CLEAR; FEMTO LDV Z8 Surgical Laser is intended for use in Corneal Lenticule Extraction for Advanced Refractive correction (CLEAR), also called Curved Lamellar Resection (CLR), for the reduction or elimination of myopia from -0.50 D to -10.00 D, with astigmatism of 0 D to -5.00 D or without astigmatism, and MRSE of -0.50 D to -12.50 D in the eye to be treated in patients who are 18 years of age or older with documentation of stable manifest refraction over the past year as demonstrated by a change in sphere and cylinder of ≤ 0.50 D in magnitude.; Other Names: Corneal lenticule extraction for advanced refractive correction

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
UCDVA (with cycloplegia)	The primary outcome is the percentage of eyes that achieve satisfactory Uncorrected Distance Visual Acuity (UCDVA) after CLEAR using the FEMTO LDV Z8, at the time point, when stability of MRSE is reached. Satisfactory UCDVA is defined as 20/40, or better, as per Snellen chart lines.	Pre-operative
UCDVA (without cycloplegia)	The primary outcome is the percentage of eyes that achieve satisfactory Uncorrected Distance Visual Acuity (UCDVA) after CLEAR using the FEMTO LDV Z8, at the time point, when stability of MRSE is reached. Satisfactory UCDVA is defined as 20/40, or better, as per Snellen chart lines.	Pre-operative
UCDVA	The primary outcome is the percentage of eyes that achieve satisfactory Uncorrected Distance Visual Acuity (UCDVA) after CLEAR using the FEMTO LDV Z8, at the time point, when stability of MRSE is reached. Satisfactory UCDVA is defined as 20/40, or better, as per Snellen chart lines.	day 1
UCDVA	The primary outcome is the percentage of eyes that achieve satisfactory Uncorrected Distance Visual Acuity (UCDVA) after CLEAR using the FEMTO LDV Z8, at the time point, when stability of MRSE is reached. Satisfactory UCDVA is defined as 20/40, or better, as per Snellen chart lines.	1 week
UCDVA	The primary outcome is the percentage of eyes that achieve satisfactory Uncorrected Distance Visual Acuity (UCDVA) after CLEAR using the FEMTO LDV Z8, at the time point, when stability of MRSE is reached. Satisfactory UCDVA is defined as 20/40, or better, as per Snellen chart lines.	1 month
UCDVA	The primary outcome is the percentage of eyes that achieve satisfactory Uncorrected Distance Visual Acuity (UCDVA) after CLEAR using the FEMTO LDV Z8, at the time point, when stability of MRSE is reached. Satisfactory UCDVA is defined as 20/40, or better, as per Snellen chart lines.	3 months
UCDVA	The primary outcome is the percentage of eyes that achieve satisfactory Uncorrected Distance Visual Acuity (UCDVA) after CLEAR using the FEMTO LDV Z8, at the time point, when stability of MRSE is reached. Satisfactory UCDVA is defined as 20/40, or better, as per Snellen chart lines.	6 months
UCDVA	The primary outcome is the percentage of eyes that achieve satisfactory Uncorrected Distance Visual Acuity (UCDVA) after CLEAR using the FEMTO LDV Z8, at the time point, when stability of MRSE is reached. Satisfactory UCDVA is defined as 20/40, or better, as per Snellen chart lines.	9 months
UCDVA	The primary outcome is the percentage of eyes that achieve satisfactory Uncorrected Distance Visual Acuity (UCDVA) after CLEAR using the FEMTO LDV Z8, at the time point, when stability of MRSE is reached. Satisfactory UCDVA is defined as 20/40, or better, as per Snellen chart lines.	12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Stability of MRSE	The percentage of eyes with: a change of less than or equal to 1.00 D of MRSE between two refractions; a change of less than or equal to 0.50 D of MRSE between two refractions will be reported for the corresponding time period.	Assessed at 3 months, 6 months, 9 months and 12 months post surgery.
Predictability of MRSE	Percentage of eyes achieving MRSE within ± 1.00 D and within ± 0.50 D of the intended outcome at the point at which MRSE stability is achieved.	Up to 12 months
Efficacy Index	Efficacy Index is defined as UCDVA at the time point, when stability of MRSE is reached, divided by CDVA at baseline: (UCDVA VX /CDVA V1). Note: "X" corresponds to the visit, when stability of MRSE will have been reached. The Efficacy Index being above the efficacy cut-off level 0.8 indicates loss of less than two lines of UCDVA	Up to 12 months
Stability of MRCYL	The stability of the manifest refractive cylinder (MRCYL) will be evaluated for the whole set of eyes treated for astigmatic myopia. The following statistics for the change in the MRCYL between two consecutive post-operative follow-up visits will be recorded: • percentage of eyes with a change in MRCYL within ±1.0 D and ±0.5 D Stability analyses will be performed on the eyes that had every follow-up exam from 1- month up to the stability time point (the Consistent Cohort), as well as on the eyes that had 2 consecutive post-op exams, but not necessarily every follow-up exam	Assessed at 3 months, 6 months, 9 months and 12 months post surgery.
Predictability of MRCYL	Percentage of eyes achieving MRCYL within ± 1.00 D of the intended outcome, and within ± 0.50 D of the intended outcome at the point at which stability of MRSE is achieved.	Up to 12 months
Vector analysis (IRC)	Intended Refractive Correction Vector (IRC) IRC = Preoperative cylinder - Target (attempted) cylinder	Pre-operative
Vector analysis (SIRC)	Assessment of change in the Surgically Induced Refractive Correction Vector (SIRC) during follow up; assessed until the MRSE stability is reached. SIRC = Preoperative cylinder - Postoperative cylinder	Assessed at 3 months, 6 months, 9 months and 12 months post surgery.
Vector analysis (EV)	Assessment of change in the Error Vector during follow up; assessed until the MRSE stability is reached. Error Vector (EV) EV = IRC - SIRC	Assessed at 3 months, 6 months, 9 months and 12 months post surgery.
Vector analysis (CR)	Assessment of change in the Correction Rate during follow up; assessed until the MRSE stability is reached. Correction Ratio (CR) CR = magnitude of SIRC / magnitude of IRC	Assessed at 3 months, 6 months, 9 months and 12 months post surgery.
Vector analysis (ER)	Assessment of change in the Error Ratio during follow up; assessed until the MRSE stability is reached. Error Ratio (ER) ER = magnitude of EV/ magnitude of IRC	Assessed at 3 months, 6 months, 9 months and 12 months post surgery.
Safety Index	Safety Index defined as CDVA at the time point, when the stability of MRSE is reached, divided by CDVA at baseline (CDVA VX / CDVA V1).	Up to 12 months
Number of Adverse Events observed in the study	Complications, including all related (Serious) Adverse Events, during surgery day and follow-up.	Up to 12 months.
Number of Device defects observed in the study	Number of device defects observed during the clinical trial.	Up to 12 months

Collaborators and Investigators

• Sponsor: Ziemer Ophthalmic Systems AG
• Collaborators: Tigermed Consulting Co., Ltd
• Investigators: Principal Investigator: Shi-hao Chen, MD, Eye Hospital, WMU

Study record dates

Study Major Dates

• Study Start (ACTUAL): November 29, 2021
• Primary Completion (ANTICIPATED): March 1, 2023
• Study Completion (ANTICIPATED): March 1, 2023

Study Registration Dates

• First Submitted: December 22, 2021
• First Submitted That Met QC Criteria: January 26, 2022
• First Posted (ACTUAL): February 8, 2022

Study Record Updates

• Last Update Posted (ACTUAL): February 8, 2022
• Last Update Submitted That Met QC Criteria: January 26, 2022
• Last Verified: December 1, 2021

More Information

Terms related to this study

• Keywords: Lenticule; CLEAR; Ziemer; FEMTO LDV; Myopic astigmatism
• Additional Relevant MeSH Terms: Eye Diseases; Refractive Errors; Astigmatism
• Other Study ID Numbers: CPFLM-0008-CN-01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No