Efficacy of FLACS USFREE Compared to Traditional Surgery Using Ultrasound.

Study hypothesis:

In cataract surgery, the FLACS USFREE technique is not inferior to the traditional phacoemulsification technique using ultrasound.

Primary Objective:

To compare non-use ultrasound FLACS (USFREE) versus traditional phacoemulsification surgery using ultrasound in eyes undergoing cataract surgery relative to the volume of BSS measured during surgery.

Secondary objective (s):

• To compare cumulative dissipated energy (CDE) used between eyes submitted to FLACS USFREE versus traditional phacoemulsification with ultrasound.
• Compare eyes submitted to FLACS USFREE versus traditional phacoemulsification surgery using ultrasound, relative to phacoemulsification time.

• Comparing eyes subjected to FLACS USFREE versus traditional phacoemulsification surgery using ultrasound 1, 7 and 30 days after surgery, for the following parameters:

  • Endothelial cell count.
  • Visual acuity.
  • Corneal topography.
  • The corneal pachymetry.
  • Intraocular pressure.
• Compare the safety profile of FLACS USFREE versus phacoemulsification surgery with ultrasound.

Study design:

Interventional, randomized, open and controlled study.

Study participants will be divided into 2 groups (FLACS without ultrasound and traditional phacoemulsification with ultrasound) and the following visits will be conducted:

• Visit -1 (pre-operative visit - day -30 to day -1 of surgery). Assessment in both eyes. If the two eyes of the research participant are eligible for the study, the eye with the least visual acuity that is designated by O1 will be selected and operated first. The second operated eye will be designated O2.
• Visit 0 (O1 surgery).
• Visit 1 (day 1 [+ 2 days] after O1 surgery).
• Visit 2 (day 7 [± 2 days] after O1 surgery).
• Visit 3 (day 30 [± 2 days] after O1 surgery).

Research participants with the second eligible eye (O2) will further perform the following assessments:

• Visit 4 (O2 surgery, which will occur on the same day of Visit 3 [+ 45 days]).
• Visit 5 (day 1 [± 2 days] after O2 surgery).
• Visit 6 (day 7 [± 2 days] after O2 surgery).
• Visit 7 (day 30 [± 2 days] after O2 surgery). Randomization process The included study participants will be allocated to one of the 2 treatment groups through computer-generated randomization (1: 1 randomization). In research participants with both eyes eligible, the surgical procedure will always be the same for both eyes.

Previously randomized and operated trial participants may not be randomized again in the study.

Concealment process:

This is an open study with no concealment procedures.

Inclusion criteria:

• Male or female gender.
• Age between 40 and 80 years (inclusive).
• Diagnosis of senile type cataract, characterized as grade II nuclear (opacity according to Lens opacities classification system II [LOCS II]), in at least 1 of the eyes.
• Obtaining the informed consent form signed by the research participant and / or legal representative.

Exclusion Criteria:

Research participants or eyes should be excluded in the presence of at least one of the following criteria:

• Cataract of degree other than II (LOCS II).
• Diabetes mellitus.
• History or presence of another ocular pathology.
• History of laser treatment (retinal or iriane).
• History of previous intraocular surgery.
• Endothelial cell count \<1500 cells / mm2.
• Corneal thickness> 700 μm.
• Dilated pupil with a diameter \<7.0 mm.
• Depth of the anterior chamber \<2.5 mm.
• Contraindications for cataract surgery, including:Active proliferative diabetic retinopathy; Rubeosis iridis and / or neovascular glaucoma; Microphthalmia; Buftalmia; The anterior uveitis; The cornea gutatta; Glaucoma; Retinal detachment.
• Other systemic or concomitant diseases that, in the opinion of the investigator, prevent the surgery from being performed or can significantly bias the results.
• Female research participant pregnant or not adhering to appropriate contraceptive measures including abstinence, hormonal contraceptives, diaphragm or condom with spermicide, intrauterine device and surgical sterilization.

Discontinuation criteria (if applicable):

• Withdrawal of consent.
• In case of death.
• Loss of follow-up before the end of the study.
• Greater protocol violation.
• Research participants who do not comply with protocol requirements.
• Any clinical condition or adverse event that, at the discretion of the investigator, impedes the continuation of the research participant in the protocol.

Expected number of eyes: 53 operated eyes per group (106 eyes in total).

Expected number of research centers:

A research center (Alfredo Tranjan Ophthalmological Center).

Selection of research participants:

Research participants followed in the research center (Alfredo Tranjan Ophthalmological Center) and indicated for cataract surgery.

Study Procedures:

Study data will be collected after obtaining the free and informed consent term. Data will be collected for questions to the research participant, consultation of their clinical records and laboratory tests and ocular tests. Surgical data will be obtained during the perioperative period.

Data collection will take place at the research center (Alfredo Tranjan Ophthalmological Center).

Data collected

• Evaluation of the eligibility criteria and signing of the free and informed consent form.
• Socio-demographic data: gender, date of birth.
• Medical history: Identification of the affected eye (s) and Date of diagnosis of cataract in each eye.
• Comorbidities and history of ocular and non-ocular surgeries.
• Non-pharmacological medications and treatments performed at the time of evaluation. Treatments received up to 3 months before the entry of the research participant will be registered.
• Urine test for detection of human chorionic gonadotrophin.
• Retinal mapping in both eyes: observation of the fundus of the eye by a retinal surgeon (the same throughout the study) with Volk 20D magnifying glass to study vessels, optic nerve, macula and retina. Data collected included absence or presence (and specification) of ocular pathology.

• Eye parameters in both eyes

  • Biometrics(Crystalline thickness (mm), Axial length of the eye (mm) and White to white corneal diameter (mm))
  • Endothelial cell count.
  • The corneal pachymetry.
  • Corneal topography.
  • Intraocular pressure.
  • Visual acuity.
• Confirmation of eligibility criteria.
• Randomization of the research participant (USFREE FLACS surgery or standard surgery).
• Volume of saline solution used during surgery.
• Start time and end of surgery.
• Phacoemulsification duration.
• CDE.
• Occurrences during surgery (complications of surgery, adaptations in the procedure).
• Adverse events (other than complications of surgery) since the last evaluation
• Changes in medications and pharmacological treatments concomitant since the last visit.
• Occurrence of adverse events.
• Changes in medications and pharmacological treatments concomitant since the last visit.
• Retinal mapping: absence or presence (and specification) of ocular pathology.

For discontinuing research participants, the primary reason for discontinuation and date of last contact within the study should be collected. Information on adverse events and changes in concomitant treatment that have occurred until discontinuation should also be obtained.

Primary outcome:

• BSS volume difference observed between eyes submitted to FLACS USFREE versus traditional phacoemulsification with ultrasound surgery.

Secondary Outcomes:

• Difference in CDE between eyes submitted to FLACS USFREE versus traditional phacoemulsification with ultrasound surgery.
• Difference in time (in seconds) of phacoemulsification during surgery, between eyes submitted to FLACS USFREE versus traditional phacoemulsification with ultrasound surgery.
• Difference in endothelial cell counts 1, 7 and 30 days after cataract surgery between eyes submitted to FLACS USFREE versus traditional phacoemulsification with ultrasound.
• Difference in visual acuity presented 1, 7 and 30 days after cataract surgery between eyes submitted to FLACS USFREE versus traditional phacoemulsification with ultrasound.
• Difference in visual acuity with better correction 1, 7 and 30 days after cataract surgery between eyes submitted to FLACS USFREE versus traditional phacoemulsification with ultrasound surgery.
• Difference in corneal topography 1, 7 and 30 days after cataract surgery between eyes submitted to FLACS USFREE versus traditional phacoemulsification with ultrasound.
• Difference in corneal pachymetry 1, 7 and 30 days after cataract surgery, between eyes submitted to FLACS USFREE versus traditional phacoemulsification with ultrasound surgery.
• Difference in intraocular pressure 1, 7 and 30 days after cataract surgery between eyes submitted to FLACS USFREE versus traditional phacoemulsification with ultrasound surgery.
• Incidence of adverse events during the study period among study participants submitted to FLACS USFREE versus traditional phacoemulsification with ultrasound.

Statistical methods

Descriptive analyzes:

For the continuous parameters the mean, standard deviation, median, minimum and maximum are given. For the categorical parameters, the cell frequencies and the percentage of research participants in each category will be given.

Primary outcome:

The BSS volume will be summarized using descriptive statistics per surgery group.

The comparison of BSS volume between groups will be determined with a 95% confidence interval, which will be estimated using the analysis of covariance with BSS volume immediately after surgery as the dependent variable, type of surgery as factor and covariables If there are statistical and clinically relevant differences between the two groups regarding their basal characteristics (eg age).

Generalized models will also be used, if applicable.

Other comparative analyzes:

• Time-to-event variables will be compared between groups using the logrank test for comparison of Kaplan-Meier curves.
• Quantitative variables will be compared between groups using the t-test for independent samples, or Mann-Whitney test in case of non-normal distribution.

The level of significance assumed in inferential analyzes will be 0.05. Inferential analysis will be bilaterial.

The data will be analyzed using SAS® Software (version 9.4; SAS Institute Inc, Cary, USA).

Duration of the study:

7 months from the beginning of the recruitment to the completion of the follow-up of the last research participant.