MyopiaNCT06774651
Comparison of Femto LDV Z8 Corneal Lenticule Extraction for Advanced Refractive Correction (CLEAR) and Visumax Small Incision Lenticule Extraction (SMILE)
An observational study of Myopia, run by Singapore Eye Research Institute at 1 site in Singapore.
Trial summary
This observational study aims to compare two laser corrective procedures for treating myopia and myopic astigmatism: a novel refractive technique, the CLEAR procedure, and the established SMILE procedure. Participants will be randomized to undergo CLEAR in one eye and SMILE in the other. Read more about this study
- Who is it for?
- Ages 21 to 50 yearsHealthy volunteers can take part
- Conditions the study is for
- Myopia
- What is being tested?
- Procedure: Corneal lenticule extraction for advanced refractive correction (CLEAR) and Procedure: Small Incision Lenticule Extraction (SMILE)
- Type of treatment
- Surgery or procedure
- How many people
- 65 participants
- Where
- 1 siteSingapore
- Study dates
- 1 Mar 2023to 31 Dec 2025
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 21 to 50 years
- All sexes
- Healthy volunteers accepted
- Adult
Study population: A total of 65 subjects (130 eyes- 65 CLEAR eyes and 65 SMILE eyes) will be recruited in the study from refractive clinic at Singapore National Eye Centre.
Who may be able to join
- >/= 21 years of age and </= 50 years of age.
- Cycloplegic spherical equivalent of >-1.00D
- Refractive cylinder -2.00 D or less; anisometropia <1.00D
- Best spectacle corrected visual acuity (BSCVA) of 6/12 or better in BOTH eyes.
- Spherical or cylindrical error has progressed at -0.50D or less per year from date of baseline measurement.
- Contact lens wearers must have removed contact lenses at least two (2) weeks before the baseline measurement.
- No evidence of irregular astigmatism on corneal topography.
- Available to attend post-operative examinations for a 12-month period.
Who cannot join
- Progressive or unstable myopia and/or astigmatism.
- Clinical or corneal topographic evidence of keratoconus.
- Patients who want bilateral SMILE procedure
- Patients who want extracted corneal lenticule to be stored for future refractive surgery.
- Residual, recurrent or active ocular disease such as uveitis, severe dry eyes, severe allergic eye disease, glaucoma, visually significant cataract and retinal disease.
- Previous corneal surgery or trauma within the corneal treatment zone.
Show all 11Show fewer
- Corneal vascularisation within 1mm of the corneal treatment zone.
- Taking systemic medications likely to affect wound healing, such as corticosteroids and antimetabolites.
- Systemically immunocompromised.
- Systemic disease likely to affect wound healing, such as diabetes, connective tissue disease and severe atopy.
- Pregnant or nursing.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Singapore1 site, 1 recruiting
- Recruiting
Singapore National Eye Centre
Singapore, S169856
Jodhbir S Mehta, MD, FRCS, 6322 7478, jodhbir.s.mehta@singhealth.com.sg
About this study
This observational study aims to compare two laser corrective procedures for treating myopia and myopic astigmatism: a novel refractive technique, the CLEAR procedure, and the established SMILE procedure. Participants will be randomized to undergo CLEAR in one eye and SMILE in the other. The investigators will evaluate and compare the two procedures based on the following aspects: refractive predictability (how accurate the vision correction is) by measuring the proportion of eyes close to the target prescription after surgery, clinical dry eye outcomes, changes in tear proteins, and corneal nerve changes at 1, 3, 6, and 12 months after both surgeries. Metabolomic features of the removed corneal tissue and how precisely the laser is centered during surgery will also be examined. Our hypothesis is that CLEAR provides equally good vision results as SMILE, and explore any extra benefits of CLEAR.
Read the detailed description
Surgical correction for refractive errors may be performed by a number of procedures. Laser correction involves refractive procedures such as laser assisted in-situ keratomileusis (LASIK), small incision lenticule extraction (SMILE), flap based refractive lenticule extraction (femtosecond lenticule extraction and pseudo-SMILE), surface ablation techniques like photorefractive keratectomy or laser epithelial keratomileusis, while lens-based corrections involve the use of phakic intra-ocular lenses.
SMILE (Visumax) is a flapless refractive procedure which was introduced in 2011 for the treatment of myopia and myopic astigmatism. In this procedure a stromal lenticule is extracted through a small incision (2.0 to 5.0 mm). It involves docking, femtosecond laser application, lenticule dissection from the surrounding stroma, and extraction. Studies have suggested that using a SMILE technique resulted in better ocular surface stability and biomechanical strength when compared with LASIK. SMILE has a steep learning curve. The most common complication encountered during the initial learning curve, is difficult lenticule dissection and extraction with an incidence of up to 16%. Other intraoperative complications include suction loss, an opaque bubble layer, and tearing of the lenticule.
Corneal Lenticule Extraction for Advanced Refractive Correction (CLEAR) by FEMTO LDV Z8 (Ziemer) is a novel technique of flapless refractive surgery which uses low energy femtosecond laser. It creates highly focused laser pulses achieving photodisruption in the low nanojoules range (<100 nJ). Decreased stromal gas generation and accurate laser focus are the advantages of this low energy concept. The advantages of CLEAR treatment are possibility of recentering the treatment area after having performed the docking, which is not possible with the VisuMax Laser System, multiple corneal incisions for easy removal of the lenticule for the beginners, trusted vacuum with minimal suction losses. Previous study concluded that the mean preoperative sphere, cylinder, and spherical equivalents were -3.05 (D), 0.50 D, and -3.30 D respectively and 1 month after CLEAR the sphere, cylinder and spherical equivalents were 0.05 D, 0.3 D and 0.12 D respectively.
As the investigators do not expect to see a great improvement to the results from the already established SMILE procedure, the investigators aim to demonstrate that CLEAR is just as good in terms of visual outcomes. However, the investigators aim to show that CLEAR has additional benefits, on top of the equal or comparative visual outcomes.
Currently there are no publications comparing the refractive predictability, higher order aberrations, changes in tear neuromediators, tear proteomics, keratocytes and nerve regeneration, corneal lenticule metabolomics, intraoperative laser centration comparing CLEAR and SMILE, hence this study will be unique in the fact that the paired eye approach will act as an internal patient control to assess the objective and subjective outcomes in patients following both these procedures.
- Conditions
- Myopia
- Being tested
- Procedure: Corneal lenticule extraction for advanced refractive correction (CLEAR), Procedure: Small Incision Lenticule Extraction (SMILE)
- Keywords
- CLEAR, FEMTO LDV Z8, SMILE, Visumax, Myopia
- Medical subject headings
- Myopia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Procedure: Corneal lenticule extraction for advanced refractive correction (CLEAR)Procedure or surgery
Routinely conducted procedure using FEMTO LDV Z8 laser system for correction of Myopia.
Procedure: Small Incision Lenticule Extraction (SMILE)Procedure or surgery
Also called SMILE
Routinely conducted procedure using VisuMax laser system for correction of Myopia.
| Study group | Role | What they receive |
|---|---|---|
| 1. CLEAR surgery eyes | Eyes that have undergone CLEAR procedures. Receives: Procedure: Procedure: Corneal lenticule extraction for advanced refractive correction (CLEAR) | |
| 2. SMILE surgery eyes | Eyes that have undergone SMILE procedures. Receives: Procedure: Procedure: Small Incision Lenticule Extraction (SMILE) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Rate of refractive predictability
Refractive predictability is defined as the proportion number of eyes achieving a postoperative spherical equivalent (SE) within ±1.0 D of the intended target. Uncorrected visual acuity (UCVA), refraction, and best corrected visual acuity (BCVA) will be recorded.
Measured: 1 year
Secondary outcomes (14)
Level of higher order aberrations
Higher-order aberrations are small optical irregularities of the eye that cannot be corrected with regular spectacles and most contact lenses. HOAs are responsible for an array of visual symptoms such as difficulty seeing at night, glare, halos, blurring, starburst patterns, or double vision.
Measured: 1 year
Tear Break Up Time (TBUT)
TBUT will be measured by determining the time interval between a complete blink and the first appearance of a dry spot on the corneal surface, indicating tear film stability.
Measured: 1 year
Concentration of tear neuromediators assessed by enzyme-linked immunosorbent assay
Tear fluid samples will be collected by the strips from Schirmer's I test. The neuromediators concentration in all tear samples will be analyzed using the enzyme-linked immunosorbent assay
Measured: 1 year
Corneal sensitivity measurements assessed by Cochet-Bonnet esthesiometer
Corneal sensitivity measurements assess the responsiveness of the cornea to external stimuli using a contact esthesiometer (Cochet-Bonnet), evaluating the functional status of corneal nerves.
Measured: 1 year
NEI score
Corneal fluorescein staining
Measured: 1 year
Oxford grading
Corneal and conjunctival staining
Measured: 1 year
Ocular Surface Disease Index (OSDI) questionnaire to measure eye symptoms and the impact of quality of life
The Ocular Surface Disease Index questionnaire is a 12-item questionnaire that used to assess the eye symptoms and and their impact on vision-related quality of life. The total Ocular Surface Disease Index score (ranging between 0 and 100) is used for evaluation, with higher scores representing greater severity of symptoms.
Measured: 1 year
Extent of keratocytes activation
In vivo confocal microscopy will be used to capture images of keratocytes at the surgical interface, with different hyperreflective states indicating varying degrees of keratocyte activation.
Measured: 1 year
Laser centration accuracy measured by the offset between the optical zone center and corneal vertex
Functional optical zone will be calculated using the software on Pentacam refractive power maps. Centration accuracy will be evaluated by the linear distance between the functional optical zone centroid and the corneal vertex.
Measured: 1 year
Metabolites profiles of corneal lenticule
Metabolomic analysis technique will be used to identify and quantify small molecules in the corneal lenticule, helping to understand metabolic pathways and physiological processes related to surgeries.
Measured: 1 year
Amount of tear production measured by Schirmer's I test
Schirmer's I test is a diagnostic method used to measure tear production by placing a standard 5 mm wide Test Strips inside the lower lid margin and assessing the amount of tear absorbed over 5 minutes.
Measured: 1 year
Abundance of tear proteins assessed by quantitative proteomic analysis
Tear fluid samples will be collected by the strips from Schirmer's I test. Quantitative proteomic analysis technique will be used to measure and compare the abundance of proteins across different samples, providing insights into protein expression, functions, and molecular interactions.
Measured: 1 year
Ocular Pain Assessment Survey (OPAS) questionnaire to measure eye pain
The Ocular Pain Assessment Survey (OPAS) is a 27-item questionnaire to evaluate the eye pain from 6 dimensions, including pain intensity for the last 24h, pain intensity for the last 2 weeks, non-eye pain intensity, quality of life, aggravating factors, associated factors and symptom relief. Each question was scored on a scale of 0-10, with higher score representing worse pain.
Measured: 1 year
Extend of corneal nerve impairment
IVCM will be used to capture corneal nerve images before and after surgeries. The extend of corneal nerve damage following surgery will be quantified using seven nerve parameters by a specialized image analysis software (ACCMetrics software).
Measured: 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Jan 2025
- Study start1 Mar 2023
- Primary completion31 Oct 2025 (estimated)
- Study completion31 Dec 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for MyopiaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 65 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Singapore Eye Research Institute
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Jodhbir S Mehta, MD, FRCS, Principal investigator, Singapore National Eye Centre
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06774651
- Sponsor's protocol ID
- R1816/58/2021
- Status last verified
- Dec 2024
- First submitted
- 30 Dec 2024
- Last updated
- 14 Jan 2025
- Results posted
- No
- Data monitoring committee
- Yes
- Individual data sharing
- No
Publications
Yu M, Liu C, Lee IXY, Hsu VW, Wong RKT, Anam A, Lim R, Mehta JS, Liu YC. Randomized controlled trial on corneal denervation, neuroinflammation and ocular surface in corneal lenticule extraction for advanced refractive correction (CLEAR) and small incision lenticule extraction (SMILE). Eye Vis (Lond). 2025 Apr 1;12(1):12. doi: 10.1186/s40662-025-00429-1.
PubMed 40165267
Study at a glance
From the registry record, last updated by the sponsor on 14 Jan 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Comparison of Femto LDV Z8 Corneal Lenticule Extraction for Advanced Refractive Correction (CLEAR) and Visumax Small Incision Lenticule Extraction (SMILE)
- ClinicalTrials.gov ID
- NCT06774651
- Acronym / sponsor ID
- R1816/58/2021
- Conditions
- Myopia
- Keywords
- CLEAR, FEMTO LDV Z8, SMILE, Visumax, Myopia
- Study type
- Observational
- Recruitment status
- Recruiting
- Enrolment
- 65 participants (estimated)
- Lead sponsor
- Singapore Eye Research InstituteUniversity, hospital or other
- Study start
- 1 Mar 2023 (actual)
- Primary completion
- 31 Oct 2025 (estimated)
- Study completion
- 31 Dec 2025 (estimated)
- First posted
- 14 Jan 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This observational study aims to compare two laser corrective procedures for treating myopia and myopic astigmatism: a novel refractive technique, the CLEAR procedure, and the established SMILE procedure. Participants will be randomized to undergo CLEAR in one eye and SMILE in the other. The investigators will evaluate and compare the two procedures based on the following aspects: refractive predictability (how accurate the vision correction is) by measuring the proportion of eyes close to the target prescription after surgery, clinical dry eye outcomes, changes in tear proteins, and corneal nerve changes at 1, 3, 6, and 12 months after both surgeries. Metabolomic features of the removed corneal tissue and how precisely the laser is centered during surgery will also be examined. Our hypothesis is that CLEAR provides equally good vision results as SMILE, and explore any extra benefits of CLEAR.
Detailed description
Surgical correction for refractive errors may be performed by a number of procedures. Laser correction involves refractive procedures such as laser assisted in-situ keratomileusis (LASIK), small incision lenticule extraction (SMILE), flap based refractive lenticule extraction (femtosecond lenticule extraction and pseudo-SMILE), surface ablation techniques like photorefractive keratectomy or laser epithelial keratomileusis, while lens-based corrections involve the use of phakic intra-ocular lenses.
SMILE (Visumax) is a flapless refractive procedure which was introduced in 2011 for the treatment of myopia and myopic astigmatism. In this procedure a stromal lenticule is extracted through a small incision (2.0 to 5.0 mm). It involves docking, femtosecond laser application, lenticule dissection from the surrounding stroma, and extraction. Studies have suggested that using a SMILE technique resulted in better ocular surface stability and biomechanical strength when compared with LASIK. SMILE has a steep learning curve. The most common complication encountered during the initial learning curve, is difficult lenticule dissection and extraction with an incidence of up to 16%. Other intraoperative complications include suction loss, an opaque bubble layer, and tearing of the lenticule.
Corneal Lenticule Extraction for Advanced Refractive Correction (CLEAR) by FEMTO LDV Z8 (Ziemer) is a novel technique of flapless refractive surgery which uses low energy femtosecond laser. It creates highly focused laser pulses achieving photodisruption in the low nanojoules range (<100 nJ). Decreased stromal gas generation and accurate laser focus are the advantages of this low energy concept. The advantages of CLEAR treatment are possibility of recentering the treatment area after having performed the docking, which is not possible with the VisuMax Laser System, multiple corneal incisions for easy removal of the lenticule for the beginners, trusted vacuum with minimal suction losses. Previous study concluded that the mean preoperative sphere, cylinder, and spherical equivalents were -3.05 (D), 0.50 D, and -3.30 D respectively and 1 month after CLEAR the sphere, cylinder and spherical equivalents were 0.05 D, 0.3 D and 0.12 D respectively.
As the investigators do not expect to see a great improvement to the results from the already established SMILE procedure, the investigators aim to demonstrate that CLEAR is just as good in terms of visual outcomes. However, the investigators aim to show that CLEAR has additional benefits, on top of the equal or comparative visual outcomes.
Currently there are no publications comparing the refractive predictability, higher order aberrations, changes in tear neuromediators, tear proteomics, keratocytes and nerve regeneration, corneal lenticule metabolomics, intraoperative laser centration comparing CLEAR and SMILE, hence this study will be unique in the fact that the paired eye approach will act as an internal patient control to assess the objective and subjective outcomes in patients following both these procedures.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 1. CLEAR surgery eyes | – | Procedure: Procedure: Corneal lenticule extraction for advanced refractive correction (CLEAR)Eyes that have undergone CLEAR procedures. |
| 2. SMILE surgery eyes | – | Procedure: Procedure: Small Incision Lenticule Extraction (SMILE)Eyes that have undergone SMILE procedures. |
Who may qualify
- Ages
- 21 to 50 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
- Study population
- A total of 65 subjects (130 eyes- 65 CLEAR eyes and 65 SMILE eyes) will be recruited in the study from refractive clinic at Singapore National Eye Centre.
Key inclusion criteria (8 listed)
- >/= 21 years of age and </= 50 years of age.
- Cycloplegic spherical equivalent of >-1.00D
- Refractive cylinder -2.00 D or less; anisometropia <1.00D
- Best spectacle corrected visual acuity (BSCVA) of 6/12 or better in BOTH eyes.
- Spherical or cylindrical error has progressed at -0.50D or less per year from date of baseline measurement.
Key exclusion criteria (11 listed)
- Progressive or unstable myopia and/or astigmatism.
- Clinical or corneal topographic evidence of keratoconus.
- Patients who want bilateral SMILE procedure
- Patients who want extracted corneal lenticule to be stored for future refractive surgery.
- Residual, recurrent or active ocular disease such as uveitis, severe dry eyes, severe allergic eye disease, glaucoma, visually significant cataract and retinal disease.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Procedure: Corneal lenticule extraction for advanced refractive correction (CLEAR)Routinely conducted procedure using FEMTO LDV Z8 laser system for correction of Myopia. | Procedure or surgery | 1. CLEAR surgery eyes |
| Procedure: Small Incision Lenticule Extraction (SMILE)Also: SMILERoutinely conducted procedure using VisuMax laser system for correction of Myopia. | Procedure or surgery | 2. SMILE surgery eyes |
Primary outcome
Rate of refractive predictability
Time frame: 1 year
Refractive predictability is defined as the proportion number of eyes achieving a postoperative spherical equivalent (SE) within ±1.0 D of the intended target. Uncorrected visual acuity (UCVA), refraction, and best corrected visual acuity (BCVA) will be recorded.
14 secondary outcomes
Level of higher order aberrations
Time frame: 1 year
Tear Break Up Time (TBUT)
Time frame: 1 year
Concentration of tear neuromediators assessed by enzyme-linked immunosorbent assay
Time frame: 1 year
Corneal sensitivity measurements assessed by Cochet-Bonnet esthesiometer
Time frame: 1 year
NEI score
Time frame: 1 year
Oxford grading
Time frame: 1 year
Ocular Surface Disease Index (OSDI) questionnaire to measure eye symptoms and the impact of quality of life
Time frame: 1 year
Extent of keratocytes activation
Time frame: 1 year
Laser centration accuracy measured by the offset between the optical zone center and corneal vertex
Time frame: 1 year
Metabolites profiles of corneal lenticule
Time frame: 1 year
Amount of tear production measured by Schirmer's I test
Time frame: 1 year
Abundance of tear proteins assessed by quantitative proteomic analysis
Time frame: 1 year
Ocular Pain Assessment Survey (OPAS) questionnaire to measure eye pain
Time frame: 1 year
Extend of corneal nerve impairment
Time frame: 1 year
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Jan 2025.
- Derived from this study: PubMed 40165267Yu M, Liu C, Lee IXY, Hsu VW, Wong RKT, Anam A, Lim R, Mehta JS, Liu YC. Randomized controlled trial on corneal denervation, neuroinflammation and ocular surface in corneal lenticule extraction for advanced refractive correction (CLEAR) and small incision lenticule extraction (SMILE). Eye Vis (Lond). 2025 Apr 1;12(1):12. doi: 10.1186/s40662-025-00429-1.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Jodhbir S Mehta, MD, FRCS principal investigator
Singapore National Eye Centre
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Myopia, run by Singapore Eye Research Institute at 1 site in Singapore.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 14 Jan 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Singapore. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Jodhbir S Mehta, MD, FRCS (6322 7478, jodhbir.s.mehta@singhealth.com.sg), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Rate of refractive predictability (time frame: 1 year). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT06774651, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 Jan 2025.