MEL90

{0} # SUMMARY OF SAFETY AND EFFECTIVENESS DATA (SSED) # I. GENERAL INFORMATION | Device Generic Name: | Excimer Laser | | --- | --- | | Device Trade Name: | MEL90 | | Device Product Code: | LZS | | Applicant's Name and Address: | Carl Zeiss Meditec, Inc. 5300 Central Parkway Dublin, California 94568 USA | | Date(s) of Panel Recommendation: | None | | Premarket Approval Application (PMA) Number: | P060004/S006 | | Date of Notice of Approval to Applicant: | December 4, 2024 | The original PMA (P060004) was approved on August 11, 2006. The MEL80 Excimer Laser is indicated for use in primary Laser Assisted in situ Keratomileusis (LASIK) treatments for the reduction or elimination of myopia of less than or equal to -7.0 D with or without refractive astigmatism of less than or equal to -3.0 D, with a maximum MRSE of -7.00 D, in patients who are 21 years of age or older with documentation of stable manifest refraction over the past year as demonstrated by change in sphere and cylinder of ≤ 0.5 D. In S001 approved on 3/28/2011, the indications for use was expanded to include reduction or elimination of naturally-occurring hyperopia of less than or equal to +5.0 D with or without refractive astigmatism of > +0.50 D and ≤ +3.0 D, with a maximum MRSE of +5.0 D, in patients who are over 21 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 ≤ 0.5 D. The SSED to support the indication is available on the CDRH website and is incorporated by reference here. The current supplement was submitted to expand the indication for the MEL90. # II. INDICATIONS FOR USE The MEL90 is indicated for use in primary Laser-Assisted in situ Keratomileusis (LASIK) treatments for the reduction or elimination of: - Myopia less in magnitude than -10.00 D sphere (in minus-cylinder notation), with and without cylinder up to -4.00 D, when MRSE is less in magnitude than -10.00 D; - Hyperopia up to +4.00 D sphere (in plus-cylinder notation), with and without cylinder up to +3.00 D, when MRSE is up to +5.00 D; and - Mixed astigmatism with cylinder from >1.00 D up to 4.00 D; 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 MRSE within +/- 0.50 D. MEL90 P060004/S006 Page 1 {1} SUMMARY OF SAFETY AND EFFECTIVENESS DATA ### III. CONTRAINDICATIONS MEL90 LASIK procedure is contraindicated in patients with: - a residual stromal bed thickness that is less than 250 microns from the corneal endothelium; - abnormal corneal topographic findings, e.g. keratoconus, pellucid marginal degeneration; - severe dry eye; - active eye infection or inflammation; - recent herpes eye infection or problems resulting from past infection; - active autoimmune disease or connective tissue disease; - uncontrolled diabetes; - uncontrolled glaucoma; - who are pregnant or nursing. ### IV. WARNINGS AND PRECAUTIONS The warnings and precautions can be found in the MEL90 labeling. ### V. DEVICE DESCRIPTION The Carl Zeiss Meditec MEL90 Excimer Laser System (see Figure 1) is designed for refractive surgery based on the ablation of corneal tissue achieved with a short pulse excimer laser having a wavelength of 193 nanometers. The laser head emits 4 to 7 nanosecond pulses (FWHM nominal pulse duration) with a repetition rate of 500 Hz. The MEL90 Excimer Laser is a spot-scanning laser that utilizes a Gaussian beam with a 0.7 mm spot diameter. MEL90 P060004/S006 Page 2 {2} SUMMARY OF SAFETY AND EFFECTIVENESS DATA **Figure 1.** MEL90 with patient supporting system LS Comfort 80 combi  The MEL90 Excimer Laser System also contains an ablation debris removal system called the Cone for Controlled Atmosphere (CCA+). The CCA+ is an airflow system that ensures constant ablation debris removal from the beam path. The MEL90 is equipped with an active eye tracking system in order to be able to align the ablation spot to eye movements by determining the center of the pupil. To supply the eye tracker with illumination, the eye of the patient is illuminated by near-infrared (NIR) light which is not visible to patients. The system determines the pupil center from an infrared (NIR) image of the patient’s eye, refreshed and processed at 1050 Hz. A green laser (532 nm) light located inside the surgical microscope and centered on its optical axis serves as a fixation target for the patient. For ease of fixation, the laser is employed in a blinking mode at a frequency of 5Hz. The fixation light blinks during the entire surgery. User control of the MEL90 Excimer Laser is implemented by a software application called the Operation Assistant (OPASS), which runs on the Main Control PC (operating system Windows 10) computer interface in order to provide the surgeon direct control over the preoperative data and an integrated application manual. The OPASS program allows the surgeon to import patient data and treatment plans, to input clinical data, and monitor the progress of the operation on a visual control panel. The Main Control PC transfers data to the Device Control (central control unit) of the excimer laser, which is fully independent and controls the operation of the excimer laser (note: the surgeon has no access to the Device Control). The MEL90 is equipped with a patient supporting system (LS Comfort 80 combi) for supporting and positioning the patient. The LS Comfort 80 combi includes motorized adjustment of the patient supporting surface. MEL90 P060004/S006 Page 3 {3} SUMMARY OF SAFETY AND EFFECTIVENESS DATA The MEL90 Excimer Laser System consists of the following major components: | Laser Arm | The Laser Arm contains the operating microscope, the debris removal system (called CCA+), the galvanometric scanners, the eye tracking camera, a portion of the optical system, the control panel and the laser arm interface. | | --- | --- | | Laser Unit | The excimer laser unit consists of the high voltage power supply, the solid state pulser circuit, the laser discharge trigger unit, and control interface board. The communication with the Device Control is done fiber-optically via the laser interface, which also optically controls the trigger unit. The laser head is provided with premix gas by the gas handling system. | | Optics | The optics form the excimer raw beam and guide it to the treatment plane by means of a beam shaper, two lenses, and different mirrors, so that a well-defined beam of Gaussian shape emerges. A vacuum pump is used to evacuate air present in the beam path; this function is initiated automatically when the laser is started. | | Device Control | The Device Control with laser control software (called POLO) provides the control of the whole laser system. It performs the following tasks: execution of the treatment (i.e. triggering of the laser head), monitoring and setting of the scanner position, control of the blower and the debris removal, communication with user interface software (called OPASS), execution of the gas management system functions, and energy control via high voltage setting and energy measuring. | | Control Panel | The control panel provides control of the distance lasers (which are used for correct height adjustment of the patient's eye), the white light illumination, and the eyetracker parameters. | | Eyetracker | A fast eyetracker unit ensures alignment of the laser beam to the eye of the patient in the working plane (2D eye tracking). It is comprised of a 1050 Hz infrared camera, an infrared LED illumination system (830 nm) and a separate control computer. | | Operating Microscope | An operating stereomicroscope (OPMI) allows the surgeon to observe the patient's eye during the treatment. | | Illumination System | An LED ring light consisting of 72 single visible light LEDs arranged in an annular pattern is mounted at the laser exit aperture for illumination of the operating area (maximum irradiance in treatment plane is 2.0 mW/cm²). In addition, there is a satellite illumination system (two visible light LEDs) mounted on the CCA+ unit to allow grazing-angle illumination of the patient's eye (maximum irradiance in treatment plane is 1.2 mW/cm²). | | Gas Handling System | The gas handling system consists of a laser gas (premix) bottle, pipes, valves, pressure sensors, vacuum pump, filters (halogen), and pressure reducers. The central control unit performs an automatic gas change on user request. The bottles are placed inside the device. | MEL90 P060004/S006 Page 4 {4} SUMMARY OF SAFETY AND EFFECTIVENESS DATA | CCA+ Debris Removal | A blower and suction unit called CCA+ debris removal provides a controlled environment at the patient's eye by removing the debris. It is mounted on a swivel arm (the entire component is referred to as the CCA+ unit), and also carries the infrared illumination. The CCA+ unit can be moved away when not in use. | | --- | --- | | Patient Supporting System | A motor-driven patient supporting system (LSC 80 combi) is movable in all 3 dimensions (X-, Y- and Z-directions). In addition, the patient headrest can be moved in the Z-direction and can be tilted in a dorsal and ventral direction. The bed can be swung out manually for easy exit of the patient. | | Slit Lamp (optional) | The slit lamp produces an evenly illuminated field in front of a reflecting prism, the geometry and color of which can be varied by the use of apertures and filters. The slit lamp has a 6V (10W) halogen bulb, a slit width of 0.15 mm to 0.75 mm, and a slit height and illumination field size of 2 mm to 12 mm (continuous). | If the MEL90 is operated in conjunction with VISUMAX 600/800, the system uses the LS Comfort 80 combi as joint patient supporting system. If the MEL90 is operated in conjunction with VisuMax, the MEL90 system also uses the patient supporting system of the VisuMax. The MEL90 can be connected to the local clinic network and to the Zeiss FORUM patient image and data management system. # MEL90 Laser Specifications | Laser Type | Argon Fluoride Excimer Laser | | --- | --- | | Laser Wavelength | 193 nm | | Laser Spot Size (FWHM diameter) | 0.7 mm ± 0.1 mm | | Laser Pulse Duration (FWHM) | 4 to 7 nanoseconds | | Laser Head Repetition Rate | 500 Hz | | Fluence (at the treatment area) | > 150 mJ/cm² (peak) | | Range of Ablation Diameter | Up to 9.2 mm (optical zone of 6.0 to 7.0 mm, diameter including a transition zone: up to 2.2 mm). The laser has a maximum ablation diameter of up to 10 mm. | | Eye-tracker, tracking frequency | 1050 Hz | MEL90 P060004/S006 Page 5 {5} SUMMARY OF SAFETY AND EFFECTIVENESS DATA | **Working distance** | 190 mm ± 0.1 mm | | --- | --- | | **Installation Requirements** | Please refer to the Instructions for Use for restrictions, tolerances or other requirements established regarding room air circulation, clearance between the laser room walls, and distance between the laser and other electronic or radiation-producing medical equipment. | | **The software versions in the laser system are as follows:** | a. OPASS Software version 4.3.4 b. Main Control PC Operating System: Image Version 4, Windows 10 c. POLO Software version 4.1.1.65 d. Eyetracker Firmware version 1.0.0.135 e. Software Package Gate Control version 1.1.2. | This laser is locked out for treatments outside the set approved and the set accepted under flagged warning treatment parameters. ## **VI. ALTERNATIVE PRACTICES OR PROCEDURES** There are several other alternatives for the correction of myopia, myopic astigmatism, hyperopia and mixed astigmatism. Alternatives to the LASIK procedure include: - Spectacle correction (glasses) - Contact lenses - Photorefractive Keratectomy (PRK) - Refractive lenticule extraction - Phakic intraocular lenses 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. MEL90 P060004/S006 Page 6 {6} SUMMARY OF SAFETY AND EFFECTIVENESS DATA ## **VII. MARKETING HISTORY** The Zeiss MEL90 is commercially available in 98 countries including the following: European Union countries, China, Canada, Brazil, Australia, Argentina, India, Iraq, Republic or Korea, Japan, Malaysia, Mexico, Saudi Arabia, the United Kingdom, Taiwan, and Vietnam. The Zeiss MEL90 has not been withdrawn from marketing for any reason relating to the safety and effectiveness of the device. ## **VIII. POTENTIAL ADVERSE EFFECTS OF THE DEVICE ON HEALTH** Below is a list of the potential adverse effects (e.g., complications) associated with the use of the device. Intraoperative complications: - Miscreated flap (perforated, lost, incomplete, too thin, misaligned, buttonhole, etc.) - Treatment interruption, difficult flap lifting with tissue damage, ocular penetration - Subconjunctival hemorrhage or bleeding Postoperative complications: - Wrinkles in flap (striae or microstriae) and/or debris or foreign body under flap and/or epithelial ingrowth under flap all of which may require a flap lift (i.e. additional surgery) - Corneal changes such as epithelial defects, haze, scarring, edema (swelling), anterior basement membrane dystrophy - Corneal ectasia (thinning) - Infection/Inflammation (e.g. conjunctivitis, corneal infiltrates/ulcer, DLK (Diffuse lamellar keratitis), SPK (Superficial punctate keratopathy), uveitis, iritis, lamellar keratitis, sterile inflammation, CTK (Central Toxic Keratopathy), corneal decompensation etc.) - Grittiness and/or ocular pain/soreness - Dry eye syndrome - Decreased or fluctuating visual acuity (uncorrected and/or best corrected visual acuity) - Inadequate treatment result (over- or under-correction, induced or residual cylinder, decentered ablation) - Worsening of visual symptoms such as glare, halos, starbursts, hazy or blurred vision, distortion, double or ghost images, fluctuation of vision, focusing difficulty, difficulty with depth perception, light sensitivity (e.g. Transient light-sensitivity syndrome (TLSS)) - Headache or eyestrain due to imbalance between the eyes - Difficulty with night driving or other low light tasks - Discomfort or pain, potentially including chronic eye pain that is resistant to therapy referred to as neuropathic corneal pain MEL90 P060004/S006 Page 7 {7} SUMMARY OF SAFETY AND EFFECTIVENESS DATA - Retinal or posterior vitreous detachment and/or vascular accidents - Ptosis - Increase in IOP - Medication intolerance (allergic reaction, etc.) - Potential risk of psychological harm Difficulties in future ophthalmic assessments: - After refractive surgery, there may be difficulties in future ophthalmic assessments, such as selecting an appropriate intraocular lens (IOL) for implantation during cataract surgery and assessing intraocular pressure (IOP). ○ It is recommended that physicians consider whether it may be useful to provide the patient their pre-operative values. Patients around 40 years of age or older may need eyeglasses for close work such as reading due to presbyopia. For the specific adverse events that occurred in the clinical study, please see Section X (Summary of Primary Clinical Study) below. ### IX. SUMMARY OF NONCLINICAL STUDIES #### A. Laboratory Studies ##### 1. Ablation Profiles To verify ablation profiles, a representative set of lenses was shot onto polymethylmethacrylate (PMMA) plates. The attempted refractive powers of the lenses were -0.0 to -10.0 D for myopia (spherical) and 0.0 to -4.0 D for myopic cylinder, 0.0 to +5.0 D for hyperopia (spherical) and 0.0 to +4.0 D for hyperopic cylinder, and +3.0 D sphere and -4.0 D cylinder for mixed astigmatism. Optical zones from 6 to 7 mm were used. Before creating each of the lenses, a fluence test was performed and a calibration lens was shot on a separate piece of PMMA to ensure correct energy setting of the laser. Each of the ablation profiles were then ablated on a PMMA plate. The PMMA plates were then measured for ablation depth, and the measurement data were exported for analysis. Profilometry curves were generated that included the actual measurement data as well as tolerance curves that represented lower and upper limits of acceptable depth values. The tolerance curves were derived from the desired curve by variation of the sphere and cylinder value by ± 10% for >3.5 D of absolute sphere and cylinder, and ± 0.35 D for <3.5 D. The results of the testing demonstrated that the profilometry met these specified requirements. ##### 2. Beam Homogeneity Measurements Beam homogeneity (profile) measurements for the MEL90 Laser System were performed by measuring the beam profile in the working plane and its variation along the optical axis, and MEL90 P060004/S006 Page 8 {8} SUMMARY OF SAFETY AND EFFECTIVENESS DATA--- by measuring the fluence, beam profile, and energy for production units. The results of the testing confirmed that the beam profile meets the specified requirements of a full width at half maximum (FWHM) beam diameter in the working plane between 0.69 mm to 0.76 mm in x and 0.67 mm to 0.72 mm in y direction. ### 3. Pulse Width and Stability The MEL90 specification for pulse width (duration) is $5.5 \pm 1.5$ ns and was verified by measurement testing. Two separate tests were conducted with similar methods, whereby the laser source was triggered from a fiber-optic signal with a predefined repetition frequency with a targeted repetition rate of 500 Hz. The results of Test 1 demonstrated that the laser output frequency measured with a photodiode and an oscilloscope was equal to the predefined input frequency. All the results were within the acceptance criteria. Test 2 used a photodiode and an oscilloscope to register 100 input and output laser pulses to determine the temporal variation of registered laser pulses (jitter) and the delay. The test results demonstrated the jitter and the delay were below the defined test limits. ### 4. Tests of Fluence Control & Fail-safe Systems The fluence of the excimer beam in the treatment plane is kept constant by controlling the energy during operation. The energy is changed by controlling the discharge high voltage value, while the spot diameter is fixed by design. The absolute value of the laser source output energy was measured with a pyroelectric sensor at 500 Hz repetition rate at different Pulse Width Modulation (PWM) values. The output energy recorded was within the predefined test values. The standard deviation was below the acceptance criterion of 5%. Several fail-safe systems are implemented in the MEL90, including those for energy, the laser scanners, the shutter, the gas system, the eye-tracker, the cone for controlled atmosphere (CCA+) debris removal system, and the laser head. The fail-safe systems were tested as part of product verification testing using MEL90 lasers that are planned for product release. To ensure that the delivered laser energy remains within tolerance, the user initiates a fluence test prior to each treatment. In addition, the overlap of the aiming beam with the working excimer beam is also checked during the fluence test. ### 5. Eye Tracking System To check the overall performance of the eye-tracker, verification tests were performed by ablating test lenses from PMMA plates that were overlayed on a tracking target. The PMMA plate and the tracking target were moved by means of a translation stage. The moving coordinates come from a pseudo-random trajectory. The refractive powers of the PMMA lenses attached to the tracking target were measured and compared to the specified limits as for the static case. ---MEL90 P060004/S006 Page 9 {9} SUMMARY OF SAFETY AND EFFECTIVENESS DATA--- Verification tests were completed to ensure that the performance of the eye-tracking and laser position correction system meets the eye tracker subsystem and MEL90 system specifications. All specifications for eye tracking control signals, monitor signals, video and graphical display data signals and functions were also tested. ## 6. Environmental Testing To ensure that the environmental conditions specified for the MEL90 do not adversely affect system performance or the operating environment for users and patients, testing was performed to verify system operation for transport and storage environmental requirements following the IEC 60601-1 standard for medical device safety and essential performance. Verification and bench testing was performed regarding potential gas hazards and the proper performance of the CCA+ plume removal system. The generation of ozone gas by the excimer laser and the leakage and/or exhaust of fluorine excimer gas from the gas containment system must fall below limits specified in the MEL90 system specifications. Verification testing was performed for the presence of both gases using appropriate gas detection apparatus. The ozone detection was performed during laser operation at a point closest to the laser aperture where ozone production is potentially the greatest. Fluorine gas was measured in the vicinity of the gas handling system and downstream of the fluorine gas-scrubbing filter during a typical excimer gas exchange procedure. The ozone measurements did not exceed the limit. The fluorine measurements showed no fluorine gas above the detection limit was present. ### B. Animal Studies Not applicable ### C. Additional Studies #### 1. Electrical Safety, Electromagnetic Compatibility, Optical Radiation Safety Testing The MEL90 was tested in-house and by accredited third-party laboratories to ensure compliance with the applicable international standards for electromagnetic compatibility, electrical safety, and laser safety. The standards for electrical safety and electromagnetic compatibility include IEC 60601-1 (General Requirements for Basic Safety and Essential Performance), IEC 60601-1-2 (Electromagnetic Compatibility Requirements and Tests), IEC 60601-2-22 (Particular Requirements for Basic Safety and Essential Performance of Surgical, Cosmetic, Therapeutic and Diagnostic Laser Equipment). The purpose of the testing was to ensure continuous device function in a noisy electromagnetic field environment. The results demonstrated the MEL90 remains functional within specifications in the presence of a range of electromagnetic frequency signals and when subjected to electrostatic dischargers. Optical radiation safety of the excimer treatment laser and the auxiliary light sources was respectively evaluated as per the requirements of IEC 60825-1 (Safety of Laser Products, Part 1-Equipment Classification) and ANSI Z80.36 (American National Standard for Ophthalmics - Light Hazard Protection for Ophthalmic Instruments). The excimer treatment ---MEL90 P060004/S006 Page 10 {10} SUMMARY OF SAFETY AND EFFECTIVENESS DATA laser was classified according to IEC 60825-1 as a Class 4 laser and the illumination system of the MEL90 was found to meet the requirements of ANSI Z80.36. 2. Software and Cybersecurity Validation Testing Carl Zeiss Meditec procedures follow IEC 62304 standard, FDA software guidance "Content of Premarket Submissions for Device Software Functions " and FDA cybersecurity guidance "Cybersecurity in Medical Devices: Quality System Considerations and Content of Premarket Submissions" and require the establishment and review of specifications, development of risk analysis, and adequate verifications and validation of software and hardware prior to release. The results of the overall software and cybersecurity validation testing demonstrate that the MEL90 meets the system specifications for performance and accuracy. 3. Human Factor Testing The MEL90 excimer laser system were evaluated based on Human factor engineering expectations in accordance with the FDA guidance "Applying Human Factors and Usability Engineering to Medical Devices" issued in February 2016. A use failure modes and effects analysis (uFMEA) summary for the MEL90 as well as comparative use-related risk analysis (cURRA) reports were created for MEL80 and MEL90. All critical user tasks were compared between the MEL80 and MEL90 to evaluate the effectiveness of the risk mitigations identified in the Risk Analysis report. The cURRA report confirmed that no new critical tasks or existing critical tasks were introduced or impacted in the MEL90 as compared to MEL80. Through this process, it was determined that all critical tasks were confirmed to be mitigated to an acceptable level of risk. The results of the overall human factor testing demonstrated that MEL90 is both safe and effective for intended users, uses, and use environments. X. SUMMARY OF PRIMARY CLINICAL STUDY The applicant performed a clinical study to establish a reasonable assurance of safety and effectiveness of LASIK with the MEL90 Excimer Laser System in treatments for the reduction or elimination of: - Myopia less in magnitude than -10.00 D sphere (in minus-cylinder notation), with and without cylinder up to -4.00 D, when MRSE is less in magnitude than -10.00 D; - Hyperopia up to +4.00 D sphere (in plus-cylinder notation), with and without cylinder up to +3.00 D, when MRSE is up to +5.00 D; and - Mixed astigmatism with cylinder from >1.00 D up to 4.00 D; in patients who are 18 years of age or older with documentation of stable manifest refraction. The study was conducted in the U.S. under IDE # G190113. Data from this clinical study was the basis for the PMA approval decision. A summary of the clinical study is presented below. MEL90 P060004/S006 Page 11 {11} SUMMARY OF SAFETY AND EFFECTIVENESS DATA ### A. Study Design Patients were treated between October 3, 2019 and October 24, 2023. The database for this Panel Track Supplement, P060004/S006, reflected data collected through 24 April 2024, and included 358 treated patients with 714 treated eyes. There were 9 investigational sites. The study was a prospective, multi-center, single-arm, unmasked clinical study. Subjects were enrolled and treated and were followed for 12 months postoperatively. Retreatments were not allowed during the study. No statistical hypothesis tests were used in key study analyses. Key study outcomes were based upon point estimates of the rates of occurrence of the key safety and effectiveness outcome parameters at the timepoint at which refractive stability was established, and upon cumulative adverse event rates for all treated eyes. #### 1. Clinical Inclusion and Exclusion Criteria Enrollment in the study was limited to subjects who met the following inclusion criteria: - Male or females must be at least 18 years of age. - Myopia up to -10.00 D with and without cylinder up to -4.00 D, or hyperopia up to +5.00 D with and without cylinder up to +4.00 D, or mixed astigmatism up to 4.00 D in magnitude; with spherical equivalent from -11.00 D through +5.00 D. - Intended treatment targeted for emmetropia in the eye(s) to be treated. - Stable refraction (within ± 0.50 D), as determined by MRSE for a minimum of 12 months prior to surgery, verified by consecutive manifest refractions and/or medical records or glasses prescription history in the eye(s) to be treated. - A difference between cycloplegic and manifest refractions of < 0.75 D spherical equivalent in the eye(s) to be treated. - For myopes, an uncorrected distance visual acuity (UCDVA) of 0.3 logMAR or worse in the eye(s) to be treated; for hyperopes and mixed astigmatism, difficulty maintaining UCDVA of 0.3 logMAR, as evidenced by the need for constant contact lens wear or spectacle wear in the eye(s) to be treated. - Best corrected distance visual acuity (BCDVA) of at least 0.0 logMAR in the eye(s) to be treated. - Must be willing to discontinue use of contact lenses for at least 2 weeks (for hard lenses) or 3 days (for soft lenses) prior to the preoperative examination, and through the day of surgery in the eye(s) to be treated. - Contact lens wearers must demonstrate a stable refraction (within ±0.5 D), as determined by MRSE, on two consecutive examinations at least 1 week apart, in the eye(s) to be treated after discontinuing contact lens use for at least 2 weeks (for hard lenses) or 3 days (for soft lenses) prior to baseline examination. Central corneal thickness of at least 480 microns in the eye(s) to be treated. Willing and able to return for scheduled follow-up examinations. Able to follow study instruction in English. Patients were not permitted to enroll in the study if they met any of the following exclusion criteria: - Anticipated residual stromal bed thickness < 250 microns in the eye(s) to be treated. - Fellow eye BCDVA worse than 0.3 logMAR. MEL90 P060004/S006 Page 12 {12} SUMMARY OF SAFETY AND EFFECTIVENESS DATA - Abnormal corneal topographic findings, e.g. keratoconus, pellucid marginal degeneration in either eye. - History of or current anterior or posterior segment pathology, including cataracts in the eye(s) to be treated. - Planned treatment for monovision. - History of any of the following medical conditions, or any other condition that could affect wound healing: collagen vascular disease, autoimmune disease, immunodeficiency diseases, endocrine disorders (including, but not limited to unstable thyroid disorders), lupus, rheumatoid arthritis, diabetes (regardless of type, duration, severity or control); active ophthalmic disease or abnormality (including, but not limited to, symptomatic blepharitis, recurrent corneal erosion, severe dry eye syndrome or symptoms, neovascularization > 1 mm from limbus), retinal detachment/repair, clinically/visually significant lens opacity, clinical evidence of trauma, corneal opacity within the central 9 mm and visible on topography, at risk for developing strabismus, or with ocular hypertension, intraocular pressure (IOP) >21 mmHg at screening or evidence of glaucoma or propensity for narrow angle glaucoma. - Residual, recurrent, active ocular or uncontrolled eyelid disease, corneal scars or other corneal abnormality such as recurrent corneal erosion or severe basement membrane disease in the eye(s) to be treated. - Ophthalmoscopic signs of progressive or unstable myopia or keratoconus suspect in either eye. - Irregular or unstable (distorted/not clear) corneal mires on central keratometry images in either eye. - History of ocular herpes zoster or herpes simplex keratitis in either eye. - Difficulty following directions or unable to fixate. - For hyperopes, clinically measurable strabismus or amblyopia in the eye(s) to be treated. - For hyperopes, white-to-white less than or equal to 11.5 mm as measured by corneal topography in the eye(s) to be treated. - For hyperopes, slit lamp examination demonstrating potentially occludable angle as judged by the investigator in the eye(s) to be treated. - Previous intraocular or corneal surgery of any kind in the eye(s) to be treated, including any type of surgery for either refractive or therapeutic purposes. - History of steroid-responsive rise in intraocular pressure, glaucoma, or preoperative IOP > 21 mmHg in either eye. - Immunocompromised or requires chronic systemic corticosteroids or other immunosuppressive therapy that may affect wound healing. - History of or has a current, clinically significant major psychiatric disorder (e.g., major depressive disorder, psychosis, schizophrenia). - Subjects with known sensitivity to planned study concomitant medications. - Enrollment in another drug or device clinical study within the prior 3 months. - Subjects who are pregnant, lactating, or of child-bearing potential and not practicing a medically approved method of birth control. Further, fellow (second) eyes of patients undergoing simultaneous, bilateral treatment were not enrolled in the study if they met any of the following exclusion criteria: MEL90 P060004/S006 Page 13 {13} SUMMARY OF SAFETY AND EFFECTIVENESS DATA - Flap complications during the first eye's surgery such as a free cap, partial flap, thin flap, or irregular flap. - Epithelial defect exceeding 2 mm x 2 mm in dimension. - Severe blepharospasm in the first eye that may have prevented or impeded the completion of the keratectomy and/or the laser ablation procedure. - Poor subject cooperation with instructions for the first eye's surgery and/or poor subject fixation on the laser fixation target. - Aborted LASIK procedure in the first eye or PRK was performed in the first eye because LASIK was not possible. ## 2. Follow-up Schedule All patients were to return for follow-up examinations per the following schedule: | Patient Screening for Eligibility | | | --- | --- | | Preoperative Evaluation: | Day -60 to Day -1 | | Operative Evaluation: | Day 0, day of surgery | | Postoperative Day 1: | Day 1 | | Postoperative Week 1: | Days 5 to 9 | | Postoperative Month 1: | Days 21 to 35 (Weeks 3 to 5) | | Postoperative Month 3: | Days 70 to 98 (Weeks 10 to 14) | | Postoperative Month 6: | Days 147 to 182 (Weeks 21 to 26) | | Postoperative Month 9: | Days 245 to 301 (Weeks 35 to 43) | | Postoperative Month 12: | Days 330 to 420 (Months 11 to 14) | The parameters to be measured preoperatively and postoperatively during the study are summarized in Table 1 below. Adverse events and complications were recorded at all visits. MEL90 P060004/S006 Page 14 {14} SUMMARY OF SAFETY AND EFFECTIVENESS DATA Table 1. Study Visits and Clinical Parameters | Visits | Preop | Op Visit | 1 Day | 7 Days | 1 Mo | 3 Mos | 6 Mos | 9 Mos | 12 Mos | Interim Visits^{1} | | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | | UCDVA | x | | x | x | x | x | x | x | x | x | | UCNVA^{2} | x | | | | | x^{2} | | | x | | | BCDVA^{3} | x | | x | x | x^{3} | x^{3} | x^{3} | x^{3} | x^{3} | x^{3} | | Objective refraction^{4} | x^{4} | | | | | | | | | | | Manifest refraction | x | | x | x | x | x | x | x | x | x | | Cycloplegic refraction | x | | | | | | | | x | | | Corneal topography | x | | | | | | | | | | | Central keratometry | x | | | | | | | | | | | Pupil size (mesopic) | x | | | | | | | | x | | | Intraocular pressure | x | | | x | x | x | x | x | x | | | Slit lamp exam | x | | x | x | x | x | x | x | x | x | | Ocular surface grading | x | | x | x | x | x | x | x | x | x^{1} | | Dilated fundus examination | x | | | | | | | | x | | | Pachymetry | x | | | | | | | | | | | Intraoperative events | | x | | | | | | | | | | Adverse events | | x | x | x | x | x | x | x | x | x | | Subject Questionnaire | x | | | | | x | x | x | x | | 1 Clinical assessments performed at interim visits beyond those indicated are at the discretion of the investigator based on the patient's condition at presentation. 2 Only for eyes treated with hyperopia with or without astigmatism. 3 If the visual acuity with spectacle correction is ≥10 letters below that obtained preoperatively, a rigid contact lens over refraction should be performed to estimate the best possible corrected visual acuity beginning at 1-month postoperatively. 4 Preoperative if needed for confirmation of cylinder magnitude. Patient reported outcomes in the IDE clinical study were obtained with the Patient Reported Outcomes with LASIK (PROWL) questionnaire with accompanying photographs, and 2 of the 3 domains of the Ocular Surface Disease Index (OSDI). The study protocol specified that the PRO instrument was to be administered at the preoperative visit and at Months 3, 6, 9, and 12 postoperatively. MEL90 P060004/S006 Page 15 {15} SUMMARY OF SAFETY AND EFFECTIVENESS DATA The key timepoints are shown below in the tables summarizing safety and effectiveness. ### 3. Clinical Endpoints With regards to safety, the primary outcomes for the study were: **Decrease in Best Corrected Distance Visual Acuity (BCDVA)** a) In eyes with preoperative BCDVA 0.0 logMAR or better, the percentage of eyes with BCDVA worse than 0.3 logMAR at the postoperative interval at which stability is established were calculated. b) Percentage of eyes with BCDVA loss ≥ 10 letters from baseline at the point at which stability is established were calculated. **Induced Manifest Refractive Astigmatism** The percentage of eyes with induced manifest refractive cylinder of > 2.00 D of absolute cylinder at the postoperative interval at which stability is established were calculated. **Incidence of Adverse Events** The rate of each type of adverse event, by the proportion of subject and eyes, were summarized. With regards to effectiveness, the primary outcomes for the study were: **Refractive Predictability** The percentage of eyes with MRSE and MRCYL within ± 1.00 D and ± 0.50 D of the intended refractive outcome at the point at which stability is established. **Uncorrected Distance Visual Acuity** The percentage of eyes with UCDVA of 0.3 logMAR or better at the point at which stability is established. With regards to success/failure criteria, the following applied: The protocol stated that refractive stability was considered to have been achieved at the latter of two postoperative refractions performed at least 3 months apart or at 3 months after surgery when compared with the 1-month interval if all the stability criteria were met. These criteria are as follows: 1. At least 95% of the treated eyes should have a change ≤ 1.00 D of MRSE, MRCYL, and vector cylinder at the latter of two postoperative refractions performed at least 3 months apart or at 3 months after surgery when compared with the 1-month interval; 2. The mean rate of change in MRSE, MRCYL, and vector cylinder, as determined by paired analysis, is ≤ 0.5 D per year (0.04 D/month) over the same time period; MEL90 P060004/S006 Page 16 {16} SUMMARY OF SAFETY AND EFFECTIVENESS DATA 3. The mean rate of change of MRSE, MRCYL, and vector cylinder decreases monotonically over time, with a projected asymptote of zero or a rate of change attributable to normal aging; 4. The 95% confidence interval for the mean rate of change includes zero or a rate of change attributable to normal aging; and 5. Stability will be confirmed at least 3 months after the stability time point by a statistically adequate subgroup. Success criteria for safety are: - < 5% of eyes with a loss of ≥ 10 letters of BCDVA at the time point at which stability is established. - < 1% of eyes with a BCDVA of 0.0 logMAR or better preoperatively that have a BCDVA of worse than 0.3 logMAR at the time point at which stability is established. - < 5% of eyes with induced manifest refractive astigmatism > 2.00 D of absolute cylinder at the time point at which stability is established. - < 1% of eyes with each ocular serious adverse event type (non-flap related) The MEL90 device will meet the acceptance criteria if the point estimates for all of the above meet or exceed the stated goal. Success criteria for effectiveness are as follows: - ≥ 85% of eyes with an uncorrected visual acuity (UCDVA) of 0.3 logMAR or better at the point at which stability is established. - ≥ 50% of eyes with a manifest refractive spherical equivalent (MRSE) within 0.50 D of intended correction at the point at which stability is established. - ≥ 75% of eyes with an MRSE within 1.00 D of intended correction at the point at which stability is established. - ≥ 95% of eyes achieve refractive stability between 2 refractions, performed at 1 and 3 months postoperatively, or over a minimum 3-month period thereafter. The MEL90 device will meet the acceptance criteria if the point estimates for all of the above meet or exceed the stated goal when evaluated by treatment cohort. # B. Accountability of PMA Cohort At the time of database lock, of the 714 eyes (of 358 subjects) enrolled and treated in the PMA study, 95.8% (684 eye) are available at the 6 months post-operative visit (the timepoint of refractive stability, the timepoint for the key safety and effectiveness analyses), with confirmatory data available on 674 eyes at the completion of the study, the 12 months postoperative visit. Of the 836 eyes of 418 subjects enrolled, 382 eyes of 195 subjects were assigned to the myopia cohort, 293 eyes of 154 subjects to the hyperopia cohort, and 157 eyes of 89 subjects to the mixed astigmatism cohort. Four eyes were not assigned: two (2) eyes of 1 subject and 2 fellow eyes of 2 subjects due to screen failure of the primary eye. MEL90 P060004/S006 Page 17 {17} SUMMARY OF SAFETY AND EFFECTIVENESS DATA Of all enrolled eyes, 122 were not treated. Of those, 98 eyes of 49 subjects and 1 eye each of 2 subjects were excluded from the study based on failure to meet inclusion criteria or meeting exclusion criteria; 8 subjects (16 eyes) withdrew consent; and 3 subjects (6 eyes) were discontinued by the investigator. As a result, 714 eyes of 358 subjects were treated, of which 358 eyes of 183 subjects received treatment for myopia, 221 eyes of 117 subjects for hyperopia, and 135 eyes of 77 subjects for mixed astigmatism. Over the course of the postoperative follow-up, greater than 92% accountability was achieved at all scheduled visits through Month 12, except Months 3 and 6 (Table 2). At Month 6 visit, percent accountability for all available eyes within-window was 89.3% and percent accountability for all available eyes completing visits whether within-window or out-of-window was 96.6%. The exam cut-off for inclusion in analyses for this report was April 24, 2024; therefore, a few eyes were still active at the time. With 6 eyes active at Month 12, the percent accountability for all available eyes within-window was 96.0% and percent accountability for all available eyes completing visits whether within-window or out-of-window was 96.6%. It should be noted that analyses supported the poolability of out-of-window data with the within-window data. **Table 2.** Postoperative Accountability for All Eyes | N=714 Eyes | | Day 1 | Week 1 | Month 1 | Month 3 | Month 6 | Month 9 | Month 12 | | --- | --- | --- | --- | --- | --- | --- | --- | --- | | Available for analysis | In or Out of Window | 712 (99.7%) | 700 (98.0%) | 686 (96.1%) | 684 (95.8%) | 684 (95.8%) | 666 (93.3%) | 674 (94.4%) | | | In Window | 712 (99.7%) | 694 (97.2%) | 654 (91.6%) | 638 (89.4%) | 632 (88.5%) | 650 (91.0%) | 670 (93.8%) | | | Out of Window | 0 (0.0%) | 6 (0.8%) | 32 (4.5%) | 46 (6.4%) | 52 (7.3%) | 16 (2.2%) | 4 (0.6%) | | Active | | 0 (0.0%) | 0 (0.0%) | 0 (0.0%) | 0 (0.0%) | 0 (0.0%) | 2 (0.3%) | 6 (0.8%) | | Discontinued | | 2 (0.3%) | 2 (0.3%) | 4 (0.6%) | 4 (0.6%) | 6 (0.8%) | 8 (1.1%) | 10 (1.4%) | | Lost to follow-up | | 0 (0.0%) | 0 (0.0%) | 0 (0.0%) | 0 (0.0%) | 2 (0.3%) | 10 (1.4%) | 16 (2.2%) | | Missed visit | Missing | 0 (0.0%) | 12 (1.7%) | 24 (3.4%) | 26 (3.6%) | 22 (3.1%) | 28 (3.9%) | 8 (1.1%) | | | Missing or Out of Window | 0 (0.0%) | 18 (2.5%) | 56 (7.8%) | 72 (10.1%) | 74 (10.4%) | 44 (6.2%) | 12 (1.7%) | | % Accountability* | In or Out of Window | 712 / 712 (100.0%) | 700 / 712 (98.3%) | 686 / 710 (96.6%) | 684 / 710 (96.3%) | 684 / 708 (96.6%) | 666 / 704 (94.6%) | 674 / 698 (96.6%) | | | In Window | 712 / 712 (100.0%) | 694 / 712 (97.5%) | 654 / 710 (92.1%) | 638 / 710 (89.9%) | 632 / 708 (89.3%) | 650 / 704 (92.3%) | 670 / 698 (96.0%) | | | Out of Window | 0 / 712 (0.0%) | 6 / 712 (0.8%) | 32 / 710 (4.5%) | 46 / 710 (6.5%) | 52 / 708 (7.3%) | 16 / 704 (2.3%) | 4 / 698 (0.6%) | \* % Accountability = Available for Analysis / (Treated - [Discontinued + Active]) For the myopia cohort of 382 enrolled eyes, 358 were treated. Twenty-four of the eyes were not treated, 20 based on failure to meet inclusion criteria or meeting exclusion criteria; 4 eyes (2 subjects) withdrew consent. MEL90 P060004/S006 Page 18 {18} SUMMARY OF SAFETY AND EFFECTIVENESS DATA For hyperopia cohort of 293 enrolled eyes, 221 were treated. Seventy-two (72) of the eyes were not treated, 62 eyes based on failure to meet inclusion criteria or meeting exclusion criteria; 6 eyes (3 subjects) withdrew consent; and 4 eyes (2 subjects) were discontinued by the investigator. For the mixed astigmatism cohort of the 157 enrolled eyes, 135 were treated. Twenty-four of the eyes were not treated, 20 due to not meeting Inclusion/Exclusion Criteria; 6 eyes (3 subjects) due to the withdrawal of consent; and 2 eyes (1 subject) was discontinued by the investigator. The accountability for each of the treatment cohorts is shown below in Tables 2.1 to 2.3. For all three cohorts, when considering eyes within-window, greater than 90% accountability was for all visits through Month 12, except Month 6 for the myopia cohort and Months 3 and 6 for the hyperopia cohort. Accountability for eyes whether within or out-of-window exceeded 95% for the myopia and mixed astigmatism cohorts. For the hyperopia cohort, accountability for eyes whether within or outside of window was at least 93% for all visits, except for Month 9 where accountability was 88.5% due to a higher number of missed visits at this exam. Each cohort had two (2) eyes still active at the Month 12 visit. **Table 2.1 - Postoperative Accountability for All Myopia Cohort Eyes** | N=358 Eyes | | Day 1 | Week 1 | Month 1 | Month 3 | Month 6 | Month 9 | Month 12 | | --- | --- | --- | --- | --- | --- | --- | --- | --- | | Available for analysis | In or Out of Window | 356 (99.4%) | 353 (98.6%) | 340 (95.0%) | 345 (96.4%) | 342 (95.5%) | 347 (96.9%) | 348 (97.2%) | | | In Window | 356 (99.4%) | 352 (98.3%) | 329 (91.9%) | 321 (89.7%) | 307 (85.8%) | 339 (94.7%) | 345 (96.4%) | | | Out of Window | 0 (0.0%) | 1 (0.3%) | 11 (3.1%) | 24 (6.7%) | 35 (9.8%) | 8 (2.2%) | 3 (0.8%) | | Active | | 0 (0.0%) | 0 (0.0%) | 0 (0.0%) | 0 (0.0%) | 0 (0.0%) | 0 (0.0%) | 2 (0.6%) | | Discontinued | | 2 (0.6%) | 2 (0.6%) | 2 (0.6%) | 2 (0.6%) | 2 (0.6%) | 2 (0.6%) | 2 (0.6%) | | Lost to follow-up | | 0 (0.0%) | 0 (0.0%) | 0 (0.0%) | 0 (0.0%) | 0 (0.0%) | 4 (1.1%) | 4 (1.1%) | | Missed visit | Missing | 0 (0.0%) | 3 (0.8%) | 16 (4.5%) | 11 (3.1%) | 14 (3.9%) | 5 (1.4%) | 2 (0.6%) | | | Missing or Out of Window | 0 (0.0%) | 4 (1.1%) | 27 (7.5%) | 35 (9.8%) | 49 (13.7%) | 13 (3.6%) | 5 (1.4%) | | % Accountability* | In or Out of Window | 356 / 356 (100.0%) | 353 / 356 (99.2%) | 340 / 356 (95.5%) | 345 / 356 (96.9%) | 342 / 356 (96.1%) | 347 / 356 (97.5%) | 348 / 354 (98.3%) | | | In Window | 356 / 356 (100.0%) | 352 / 356 (98.9%) | 329 / 356 (92.4%) | 321 / 356 (90.2%) | 307 / 356 (86.2%) | 339 / 356 (95.2%) | 345 / 354 (97.5%) | | | Out of Window | 0 / 356 (0.0%) | 1 / 356 (0.3%) | 11 / 356 (3.1%) | 24 / 356 (6.7%) | 35 / 356 (9.8%) | 8 / 356 (2.2%) | 3 / 354 (0.8%) | Subject (01-074) experienced a seizure prior to undergoing treatment with the MEL90. the procedure was not completed, the subject was discontinued due to the unrelated medical event. * % Accountability = Available for Analysis / (Treated - [Discontinued + Active]) MEL90 P060004/S006 Page 19 {19} SUMMARY OF SAFETY AND EFFECTIVENESS DATA **Table 2.2 - Postoperative Accountability for All Hyperopia Cohort Eyes** | N=221 Eyes | | Day 1 | Week 1 | Month 1 | Month 3 | Month 6 | Month 9 | Month 12 | | --- | --- | --- | --- | --- | --- | --- | --- | --- | | Available for analysis | In or Out of Window | 221 (100.0%) | 213 (96.4%) | 219 (99.1%) | 210 (95.0%) | 210 (95.0%) | 193 (87.3%) | 199 (90.0%) | | | In Window | 221 (100.0%) | 213 (96.4%) | 205 (92.8%) | 193 (87.3%) | 202 (91.4%) | 189 (85.5%) | 199 (90.0%) | | | Out of Window | 0 (0.0%) | 0 (0.0%) | 14 (6.3%) | 17 (7.7%) | 8 (3.6%) | 4 (1.8%) | 0 (0.0%) | | Active | | 0 (0.0%) | 0 (0.0%) | 0 (0.0%) | 0 (0.0%) | 0 (0.0%) | 0 (0.0%) | 2 (0.9%) | | Discontinued | | 0 (0.0%) | 0 (0.0%) | 0 (0.0%) | 0 (0.0%) | 1 (0.5%) | 3 (1.4%) | 5 (2.3%) | | Lost to follow-up | | 0 (0.0%) | 0 (0.0%) | 0 (0.0%) | 0 (0.0%) | 2 (0.9%) | 6 (2.7%) | 11 (5.0%) | | Missed visit | Missing | 0 (0.0%) | 8 (3.6%) | 2 (0.9%) | 11 (5.0%) | 8 (3.6%) | 19 (8.6%) | 4 (1.8%) | | | Missing or Out of Window | 0 (0.0%) | 8 (3.6%) | 16 (7.2%) | 28 (12.7%) | 16 (7.2%) | 23 (10.4%) | 4 (1.8%) | | % Accountability* | In or Out of Window | 221 / 221 (100.0%) | 213 / 221 (96.4%) | 219 / 221 (99.1%) | 210 / 221 (95.0%) | 210 / 220 (95.5%) | 193 / 218 (88.5%) | 199 / 214 (93.0%) | | | In Window | 221 / 221 (100.0%) | 213 / 221 (96.4%) | 205 / 221 (92.8%) | 193 / 221 (87.3%) | 202 / 220 (91.8%) | 189 / 218 (86.7%) | 199 / 214 (93.0%) | | | Out of Window | 0 / 221 (0.0%) | 0 / 221 (0.0%) | 14 / 221 (6.3%) | 17 / 221 (7.7%) | 8 / 220 (3.6%) | 4 / 218 (1.8%) | 0 / 214 (0.0%) | \* % Accountability = Available for Analysis / (Treated - [Discontinued + Active]) MEL90 P060004/S006 Page 20 {20} SUMMARY OF SAFETY AND EFFECTIVENESS DATA **Table 2.3 - Postoperative Accountability for All Mixed Astigmatism Cohort Eyes** | N=135 Eyes | | Day 1 | Week 1 | Month 1 | Month 3 | Month 6 | Month 9 | Month 12 | | --- | --- | --- | --- | --- | --- | --- | --- | --- | | Available for analysis | In or Out of Window | 135 (100.0%) | 134 (99.3%) | 127 (94.1%) | 129 (95.6%) | 132 (97.8%) | 126 (93.3%) | 127 (94.1%) | | | In Window | 135 (100.0%) | 129 (95.6%) | 120 (88.9%) | 124 (91.9%) | 123 (91.1%) | 122 (90.4%) | 126 (93.3%) | | | Out of Window | 0 (0.0%) | 5 (3.7%) | 7 (5.2%) | 5 (3.7%) | 9 (6.7%) | 4 (3.0%) | 1 (0.7%) | | Active | | 0 (0.0%) | 0 (0.0%) | 0 (0.0%) | 0 (0.0%) | 0 (0.0%) | 2 (1.5%) | 2 (1.5%) | | Discontinued | | 0 (0.0%) | 0 (0.0%) | 2 (1.5%) | 2 (1.5%) | 3 (2.2%) | 3 (2.2%) | 3 (2.2%) | | Lost to follow-up | | 0 (0.0%) | 0 (0.0%) | 0 (0.0%) | 0 (0.0%) | 0 (0.0%) | 0 (0.0%) | 1 (0.7%) | | Missed visit | Missing | 0 (0.0%) | 1 (0.7%) | 6 (4.4%) | 4 (3.0%) | 0 (0.0%) | 4 (3.0%) | 2 (1.5%) | | | Missing or Out of Window | 0 (0.0%) | 6 (4.4%) | 13 (9.6%) | 9 (6.7%) | 9 (6.7%) | 8 (5.9%) | 3 (2.2%) | | % Accountability* | In or Out of Window | 135 / 135 (100.0%) | 134 / 135 (99.3%) | 127 / 133 (95.5%) | 129 / 133 (97.0%) | 132 / 132 (100.0%) | 126 / 130 (96.9%) | 127 / 130 (97.7%) | | | In Window | 135 / 135 (100.0%) | 129 / 135 (95.6%) | 120 / 133 (90.2%) | 124 / 133 (93.2%) | 123 / 132 (93.2%) | 122 / 130 (93.8%) | 126 / 130 (96.9%) | | | Out of Window | 0 / 135 (0.0%) | 5 / 135 (3.7%) | 7 / 133 (5.3%) | 5 / 133 (3.8%) | 9 / 132 (6.8%) | 4 / 130 (3.1%) | 1 / 130 (0.8%) | \* % Accountability = Available for Analysis / (Treated - [Discontinued + Active]) MEL90 P060004/S006 Page 21 {21} SUMMARY OF SAFETY AND EFFECTIVENESS DATA ### C. Study Population Demographics and Baseline Parameters The demographics of the study population are typical for a LASIK study performed in the US. A summary of demographic information for all treated subjects is provided in Table 3, with stratification by subjects treated for each cohort: myopia, hyperopia, and mixed astigmatism. The proportions enrolled are consistent with the sex, gender, age, racial and ethnic prevalence of patients who get LASIK surgery in the US. **Table 3.** Demographics for All Treated Subjects by Treatment Cohort | | | Myopia | | Hyperopia | | Mixed Astigmatism | | Total | | | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | | | | N (%) | | N (%) | | N (%) | | n/N (%) | | | Gender | Male | 88/183 | (48.1%) | 52/117 | (44.4%) | 46/77 | (59.7%) | 177/358 | (49.4%) | | | Female | 95/183 | (51.9%) | 65/117 | (55.6%) | 31/77 | (40.3%) | 181/358 | (50.6%) | | Race | White | 167/183 | (91.3%) | 109/117 | (93.2%) | 71/77 | (92.2%) | 329/358 | (91.9%) | | | Black | 4/183 | (2.2%) | 6/117 | (5.1%) | 1/77 | (1.3%) | 11/358 | (3.1%) | | | Asian | 8/183 | (4.4%) | 0/117 | (0.0%) | 0/77 | (0.0%) | 8/358 | (2.2%) | | | Other | 4/183 | (2.2%) | 2/117 | (1.7%) | 5/77 | (6.5%) | 10/358 | (2.8%) | | Ethnicity | Hispanic or Latino | 13/183 | (7.1%) | 8/117 | (6.8%) | 10/77 | (13.0%) | 28/358 | (7.8%) | | | Not Hispanic or Latino | 170/183 | (92.9%) | 109/117 | (93.2%) | 67/77 | (87.0%) | 330/358 | (92.2%) | | Age (years) | Mean (SD) | 33.1 (7.5) | | 39.9 (11.5) | | 35.3 (9.1) | | 35.7 (9.6) | | | | Median | 32.0 | | 42.0 | | 35.0 | | 34.0 | | | | Min, Max | 19, 63 | | 18, 62 | | 20, 57 | | 18, 63 | | | Age Category | Age 18 to < 22 | 9/183 | (4.9%) | 5/117 | (4.3%) | 6/77 | (7.8%) | 18/358 | (5.0%) | | | Age 22 and older | 174/183 | (95.1%) | 112/117 | (95.7%) | 71/77 | (92.2%) | 340/358 | (95.0%) | Abbreviations: SD=Standard Deviation. Note: Of 418 Subjects enrolled, 417 were assigned to cohorts, and 358 treated. 19 had OD and OS assigned to a different cohort (8 were assigned to myopia and mixed astigmatism and 11 to hyperopia and mixed astigmatism). Therefore, the number of subjects in tables of the 3 cohorts will sum to more than the number of subjects in the overall table. Note that only treated subjects are summarized. The preoperative manifest refractive sphere (MRSPH) and cylinder (MRCYL) are the key baseline parameters for clinically relevant variables important for understanding the safety and treatment effects. Tables 4.1 and 4.2 show the distribution of baseline MRSPH and MRCYL for all treated eyes, with stratification by subjects treated for each cohort: myopia, hyperopia, and mixed astigmatism. For these tables, the baseline refraction is represented in minus cylinder form for all cohorts. As a result, 11 eyes in the hyperopia cohort have a MRSPH greater than +5.00 D in minus cylinder form; however, these same eyes are within the treatment range of +5.00 D MRSPH when represented in plus cylinder form. **Table 4.1.** Preoperative Manifest Refraction Sphere (MRSPH) for All Eyes MEL90 P060004/S006 Page 22 {22} # SUMMARY OF SAFETY AND EFFECTIVENESS DATA | Cohort | Myopia Eyes | | Hyperopia Eyes | | Mixed Astigmatism Eyes | | Total Eyes | | | --- | --- | --- | --- | --- | --- | --- | --- | --- | | | N | (%) | N | (%) | N | (%) | N | (%) | | **Manifest Refraction Sphere (D)** | | | | | | | | | | -10.00 to -9.01 D | 26/358 | (7.3%) | | | | | 26/714 | (3.6%) | | -9.00 to -8.01 D | 28/358 | (7.8%) | | | | | 28/714 | (3.9%) | | -8.00 to -7.01 D | 26/358 | (7.3%) | | | | | 26/714 | (3.6%) | | -7.00 to -6.01 D | 29/358 | (8.1%) | | | | | 29/714 | (4.1%) | | -6.00 to -5.01 D | 42/358 | (11.7%) | | | | | 42/714 | (5.9%) | | -5.00 to -4.01 D | 38/358 | (10.6%) | | | | | 38/714 | (5.3%) | | -4.00 to -3.01 D | 45/358 | (12.6%) | | | | | 45/714 | (6.3%) | | -3.00 to -2.01 D | 47/358 | (13.1%) | | | | | 47/714 | (6.6%) | | -2.00 to -1.01 D | 48/358 | (13.4%) | | | | | 48/714 | (6.7%) | | -1.00 to -0.01 D | 25/358 | (7.0%) | | | | | 25/714 | (3.5%) | | 0.00 D | 4/358 | (1.1%) | 0/221 | (0.0%) | 0/135 | (0.0%) | 4/714 | (0.6%) | | +0.01 to +1.00 D | | | 15/221 | (6.8%) | 77/135 | (57.0%) | 92/714 | (12.9%) | | +1.01 to +2.00 D | | | 50/221 | (22.6%) | 26/135 | (19.3%) | 76/714 | (10.6%) | | +2.01 to +3.00 D | | | 55/221 | (24.9%) | 23/135 | (17.0%) | 78/714 | (10.9%) | | +3.01 to +4.00 D | | | 48/221 | (21.7%) | 9/135 | (6.7%) | 57/714 | (8.0%) | | +4.01 to +5.00 D | | | 42/221 | (19.0%) | | | 42/714 | (5.9%) | | +5.01 to +6.00 D | | | 10/221 | (4.5%) | | | 10/714 | (1.4%) | | +6.01 to +7.00 D | | | 1/221 | (0.5%) | | | 1/714 | (0.1%) | | **Manifest Refraction Sphere (D)** | | | | | | | | | | N | 358 | | 221 | | 135 | | 714 | | | Mean (SD) | -4.64 (2.74) | | +2.97 (1.31) | | +1.26 (0.99) | | -1.17 (4.12) | | | Median | -4.50 | | 3.00 | | +1.00 | | 0.00 | | | Min, Max | -10.0, 0.00 | | +0.75, +6.25 | | +0.25, +3.50 | | -10.0, +6.25 | | Abbreviations: SD=Standard Deviation. *Shaded cells: Treatment of > +4.00 D sphere (in plus-cylinder notation) will present a flagged warning to the user indicating that correction of these powers is outside the range of the approved indications for use. MEL90 P060004/S006 Page 23 {23} SUMMARY OF SAFETY AND EFFECTIVENESS DATA **Table 4.2.** Preoperative Manifest Refraction Cylinder (MRCYL) for All Eyes | Cohort | Myopia Eyes | | Hyperopia Eyes | | Mixed Astigmatism Eyes | | Total Eyes | | | --- | --- | --- | --- | --- | --- | --- | --- | --- | | | N | (%) | N | (%) | N | (%) | N | (%) | | **Manifest Refraction Cylinder (D)** | | | | | | | | | | -3.01 to -4.00 D* | 24/358 | (6.7%) | 12/221* | (5.4%) | 51/135 | (37.8%) | 87/714 | (12.2%) | | -2.01 to -3.00 D | 34/358 | (9.5%) | 26/221 | (11.8%) | 39/135 | (28.9%) | 99/714 | (13.9%) | | -1.01 to -2.00 D | 65/358 | (18.2%) | 29/221 | (13.1%) | 30/135 | (22.2%) | 124/714 | (17.4%) | | -1.00 D** | 25/358 | (7.0%) | 23/221 | (10.4%) | 13/135** | (9.6%) | 61/714 | (8.5%) | | -0.75 D** | 44/358 | (12.3%) | 29/221 | (13.1%) | 2/135** | (1.5%) | 75/714 | (10.5%) | | -0.50 D*** | 37/358 | (10.3%) | 26/221 | (11.8%) | 0/135*** | (0.0%) | 63/714 | (8.8%) | | -0.25 D*** | 37/358 | (10.3%) | 18/221 | (8.1%) | 0/135*** | (0.0%) | 55/714 | (7.7%) | | 0.00 D*** | 92/358 | (25.7%) | 58/221 | (26.2%) | 0/135*** | (0.0%) | 150/714 | (21.0%) | | **Manifest Refraction Cylinder (D)** | | | | | | | | | | N | 358 | | 221 | | 135 | | 714 | | | Mean (SD) | -1.002 (1.048) | | -0.988 (1.040) | | -2.602 (0.992) | | -1.300 (1.210) | | | Median | -0.75 | | -0.75 | | -2.75 | | -1.00 | | | Min, Max | -4.00, 0.00 | | -4.00, 0.00 | | -4.00, -0.75 | | -4.00, 0.00 | | Abbreviations: SD=Standard Deviation. Shaded cells: * Treatments of hyperopia with cylinder magnitude > 3.00 D through 4.0 D will present a flagged warning to the user indicating that correction of these powers is outside the range of the approved indications for use. ** Treatments of mixed astigmatism with cylinder magnitude up to 0.50 D will be locked out. *** Treatments of mixed astigmatism with cylinder magnitude > 0.50 D through 1.00 D will present a flagged warning to the user indicating that correction of these powers is outside the range of the approved indications for use. ## D. Safety and Effectiveness Results ### 1. Safety Results The analysis of safety was based on eyes in the Safety Population, defined as “eyes with attempted LASIK (successful or aborted after initiation of flap).” The Safety Population includes all 714 eyes treated in the study available for the 6-month evaluation. This section presents key safety outcomes, BCDVA, adverse events and patient-reported outcomes. The key safety outcomes for this study are presented below in Table 5 to Table 6.1. Adverse effects are reported in Tables 7 to 7.3. Key safety outcomes at the last available visit for each of the 714 eyes in the Safety Population are summarized in Table 5. No study subject presented with a loss of ≥ 2 lines BCDVA or with BCDVA worse than 0.3 logMAR at the last available visit. One subject (**Subject 08-001 OS**) presented with increased manifest refractive astigmatism > 2.00 D at the last available visit, this subject had a user transcription error which led to the wrong treatment axis. MEL90 P060004/S006 Page 24 {24} SUMMARY OF SAFETY AND EFFECTIVENESS DATA Table 5. Key Safety Outcomes at Last Available Visit for All Eyes in Safety Population | Key Safety Outcome | Myopia n/N (%) | Hyperopia n/N (%) | Mixed Astigmatism n/N (%) | Total n/N (%) | | --- | --- | --- | --- | --- | | Loss of ≥ 2 lines BCDVA | 0/358 (0%) | 0/221 (0%) | 0/135 (0%) | 0/714 (0%) | | Loss of > 2 lines BCDVA | 0/358 (0%) | 0/221 (0%) | 0/135 (0%) | 0/714 (0%) | | BCDVA worse than 0.3 logMAR | 0/358 (0%) | 0/221 (0%) | 0/135 (0%) | 0/714 (0%) | | BCDVA worse than 0.3 logMAR if 0.0 logMAR or better preoperatively | 0/358 (0%) | 0/221 (0%) | 0/135 (0%) | 0/714 (0%) | | Increased manifest refractive astigmatism > 2.00D | 0/358 (0%) | 0/221 (0%) | 1/135 (0.7%) | 1/714 (0.1%) | The primary safety outcomes for the study were defined in the protocol as: - the percentage of eyes with preoperative BCDVA 0.0 logMAR or better with BCDVA worse than 0.3 logMAR at timepoint of refractive stability; - the percentage of eyes with BCDVA loss ≥ 10 letters from baseline at the point of refractive stability; - The percentage of eyes with induced manifest refractive cylinder of > 2.00 D of absolute cylinder at the timepoint of refractive stability; - The rate of each type of adverse event, by the proportion of subject and eyes. Stability was determined at the 6-month postoperative visit (see section “Stability of MRSE”). Table 5.1 summarizes the results for the primary safety outcomes at 6 months for all eyes and for each treatment cohort separately. The results on adverse events are summarized further below (Table 6 and Tables 6.1 to 6.3). At the timepoint of refractive stability, one eye, which had been treated for myopia, experienced a transient loss of BCDVA ≥2 lines. As described above, one eye presented with increased manifest refractive astigmatism > 2.00 D due to a treatment on the wrong axis. The eye was retreated before the 3-month visit (the last observation prior to retreatment was carried forward for this one eye); the 1 Month data showing induced astigmatism has been carried through to all visits for safety analysis. Table 5.1. Primary Safety Outcomes at 6 months for All Eyes in Safety Population | Key Safety Outcome | Myopia n/N (%) | Hyperopia n/N (%) | Mixed Astigmatism n/N (%) | Total n/N (%) | | --- | --- | --- | --- | --- | | Loss of ≥ 2 lines BCDVA | 1/342 (0.3%) | 0/210 (0%) | 0/133 (0%) | 1/685 (0.2%) | | BCDVA worse than 0.3 logMAR if 0.0 logMAR or better preoperatively | 1/342 (0.3%) | 0/210 (0%) | 0/133 (0%) | 1/685 (0.2%) | | Increased manifest refractive astigmatism > 2.00D | 0/342 (0%) | 0/210 (0%) | 1/133 (0.8%) | 1/685 (0.2%) | Data for subject 08-001 OS Month 1 was carried forward through all post-operative visits for safety analysis. MEL90 P060004/S006 Page 25 {25} SUMMARY OF SAFETY AND EFFECTIVENESS DATA # **Best Corrected Distance Visual Acuity (BCDVA)** The gain and loss of BCDVA from baseline across visits for the full cohort is presented in Table 6. Regarding the key safety outcome of loss of 2 or more lines of BCDVA, five eyes experienced such loss temporarily at 1 month postoperatively or later. Three eyes are in the myopia cohort and two eyes in the hyperopia cohort; no eyes in the mixed astigmatism cohort had a loss of 2 or more lines of BCDVA. **Table 6.** Change in Best Corrected Visual Acuity for All Eyes in Safety Population | | Day 1 n (%) | Week 1 n (%) | Month 1 n (%) | Month 3 n (%) | Month 6 n (%) | Month 9 n (%) | Month 12 n (%) | Unsched.^{3} n (%) | | --- | --- | --- | --- | --- | --- | --- | --- | --- | | Lost > 2 lines (>10 letters) | 19 (2.7%) | 3 (0.4%) | 2 (0.3%) | 1 (0.2%) | 1 (0.2%) | 0 (0%) | 0 (0%) | 4 (8.3%) | | Lost 2 lines (10 letters) | 12 (1.7%) | 1 (0.1%) | 1 (0.2%) | 0 (0%) | 0 (0%) | 0 (0%) | 0 (0%) | 0 (0%) | | Lost 1 line (5-9 letters) | 85 (11.9%) | 74 (10.6%) | 36 (5.3%) | 24 (3.5%) | 35 (5.1%) | 19 (2.9%) | 21 (3.1%) | 2 (4.2%) | | Unchanged (< 5 letters) | 516 (72.5%) | 518 (74.0%) | 519 (75.7%) | 526 (76.9%) | 508 (74.2%) | 504 (75.6%) | 488 (72.3%) | 39 (81.3%) | | Gained 1 line (5-9 letters) | 76 (10.7%) | 102 (14.6%) | 117 (17.1%) | 118 (17.3%) | 129 (18.8%) | 125 (18.7%) | 152 (22.5%) | 3 (6.3%) | | Gained 2 lines (10 letters) | 4 (0.6%) | 2 (0.3%) | 9 (1.3%) | 13 (1.9%) | 5 (0.7%) | 12 (1.8%) | 10 (1.5%) | 0 (0%) | | Gained > 2 lines (>10 letters) | 0 (0%) | 0 (0%) | 2 (0.3%) | 2 (0.3%) | 7 (1.0%) | 7 (1.1%) | 4 (0.6%) | 0 (0%) | | Not Reported | 0 | 12 | 24 | 26 | 22 | 28 | 8 | | | Total with Data^{1} | 712 | 700 | 686 | 684 | 685 | 667 | 675 | 48 | | On Study^{2} | 712 | 712 | 710 | 710 | 706 | 694 | 682 | | Percentages are based on non-missing counts. $^{1}$ Data for subject 08-001 OS Month 1 was carried forward through all post-operative visits $^{2}$ On-study represents the number of eyes not discontinued, LTF, or active at that visit. $^{3}$ Note that for eyes with more than one interim visit, the worst logMAR value was selected Outlined rows represent results associated with safety. MEL90 P060004/S006 Page 26 {26} SUMMARY OF SAFETY AND EFFECTIVENESS DATA The gain and loss of BCDVA at Month 6, stratified by treatment cohort, is presented in Table 6.1. **Table 6.1.** Change in Best Corrected Visual Acuity at Month 6 Stratified by Treatment Cohort for All Eyes in Safety Population | | Myopia Cohort n (%) | Hyperopia Cohort n (%) | Mixed Astigmatism n (%) | Total n (%) | | --- | --- | --- | --- | --- | | Lost > 2 lines (>10 letters) | 1 (0.3%) | 0 (0%) | 0 (0%) | 1 (0.2%) | | Lost 2 lines (10 letters) | 0 (0%) | 0 (0%) | 0 (0%) | 0 (0%) | | Lost 1 line (5-9 letters) | 11 (3.2%) | 19 (9.1%) | 5 (3.8%) | 35 (5.1%) | | Unchanged (< 5 letters) | 246 (71.9%) | 162 (77.1%) | 100 (75.2%) | 508 (74.2%) | | Gained 1 line (5-9 letters) | 76 (22.2%) | 27 (12.9%) | 26 (19.6%) | 129 (18.8%) | | Gained 2 lines (10 letters) | 3 (0.9%) | 1 (0.5%) | 1 (0.8%) | 5 (0.7%) | | Gained > 2 lines (>10 letters) | 5 (1.5%) | 1 (0.5%) | 1 (0.8%) | 7 (1.0%) | | Not Reported | 14 | 8 | 0 | 22 | | Total with Data | 342 | 210 | 133 | 685 | | On Study^{1,2} | 356 | 218 | 132 | 706 | $^{1}$ Data for subject 08-001 OS Month 1 was carried forward through all post-operative visits. Note: Month 3 through Month 12 data includes 1 additional eye “with data” than “on study” due to this additional data point. $^{2}$ On-study represents the number of eyes not discontinued, LTF, or active at that visit. Outlined rows represent results associated with safety. ### Adverse effects that occurred in the PMA clinical study Intraoperative and postoperative adverse events are reported in **Table 7** for all eyes, followed by **Tables 7.1 to 7.3** for each treatment cohort. One intraoperative event, interface debris, occurred at a rate above 1.0% (2.0%, 14/714). There were two (2) postoperative adverse events which occurred at a 1.0% incidence or greater, patient complaint of dry eye (2.8%, 20/714) and epithelium in the interface (1.1%, 8/714). There were three serious adverse events in the postoperative course for a retinal detachment, a flap melt, and hospitalization for a seizure event. Three secondary surgical interventions were performed for epithelial ingrowth removal, for retreatment of an incorrect treatment axis, and for a scleral buckle procedure. No unanticipated adverse device effects (UADEs) were reported. MEL90 P060004/S006 Page 27 {27} SUMMARY OF SAFETY AND EFFECTIVENESS DATA **Table 7. Adverse Events for All Eyes** | | Subjects with 1 or More AE | | Eyes with 1 or More AE | | Events | | | --- | --- | --- | --- | --- | --- | --- | | | n/N | % | n/N | % | # | | | **Adverse Events** | | | | | | | | One or More of Any Adverse Event | 59/358 | 16.5% | 84/714 | 11.8% | 106 | | | **Intraoperative Adverse Events** | | | | | | | | Interface debris | 10/358 | 2.8% | 14/714 | 2.0% | 15 | | | Flap is not of the size and shape as initially intended | 1/358 | 0.3% | 1/714 | 0.1% | 1 | | | Flap misaligned | 1/358 | 0.3% | 1/714 | 0.1% | 1 | | | Flap tear | 1/358 | 0.3% | 1/714 | 0.1% | 1 | | | Free cap | 1/358 | 0.3% | 1/714 | 0.1% | 1 | | | Hinge tissue ablated | 1/358 | 0.3% | 1/714 | 0.1% | 1 | | | Treatment was on wrong Axis | 1/358 | 0.3% | 1/714 | 0.1% | 1 | | | Procedure interruption due to seizure | 1/358 | 0.3% | 2/714 | 0.3% | 2 | | | **Postoperative Adverse Events** | | | | | | | | Clinical signs and subjective symptoms reported by the patient consistent with dry eye | 13/358 | 3.6% | 20/714 | 2.8% | 23 | | | Epithelium in the interface | 6/358 | 1.7% | 8/714 | 1.1% | 9 | | | Diffuse lamellar keratitis (Grade 2 or less) | 6/358 | 1.7% | 6/714 | 0.8% | 6 | | | Corneal edema between 1 week and 1 month after the procedure | 2/358 | 0.6% | 4/714 | 0.6% | 4 | | | Corneal striae | 3/358 | 0.8% | 4/714 | 0.6% | 4 | | | Conjunctivitis, allergic | 2/358 | 0.6% | 3/714 | 0.4% | 3 | | | Corneal abrasion | 3/358 | 0.8% | 3/714 | 0.4% | 3 | | | Conjunctivitis, viral | 1/358 | 0.3% | 2/714 | 0.3% | 2 | | | Epithelium in the interface with loss of 10 letters or more of BCDVA | 1/358 | 0.3% | 1/714 | 0.1% | 2 | | | MGD (Meibomian Gland Dysfunction) | 1/358 | 0.3% | 2/714 | 0.3% | 2 | | | Posterior Vitreous Detachment (PVD) | 1/358 | 0.3% | 2/714 | 0.3% | 2 | | | Transient light sensitivity syndrome (TLSS) | 1/358 | 0.3% | 2/714 | 0.3% | 2 | | | Vitreous syneresis | 1/358 | 0.3% | 2/714 | 0.3% | 2 | | | Anterior uveitis | 1/358 | 0.3% | 1/714 | 0.1% | 1 | | | Chemical splash in eye | 1/358 | 0.3% | 1/714 | 0.1% | 1 | | | Conjunctival laceration | 1/358 | 0.3% | 1/714 | 0.1% | 1 | | | Corneal dryness | 1/358 | 0.3% | 1/714 | 0.1% | 1 | | | Corneal edema at 1 month or later | 1/358 | 0.3% | 1/714 | 0.1% | 1 | | | Decrease in BCDVA ≥ 10 letters not due to irregular astigmatism at ≥ 3 months | 1/358 | 0.3% | 1/714 | 0.1% | 1 | | | Epithelial defect | 1/358 | 0.3% | 1/714 | 0.1% | 1 | | | Foreign body | 1/358 | 0.3% | 1/714 | 0.1% | 1 | | | Foreign body sensation | 1/358 | 0.3% | 1/714 | 0.1% | 1 | | | IOP increase of > 10 mmHg above baseline on 2 consec. exams or IOP > 30 mmHg on 2 consec. exams | 1/358 | 0.3% | 1/714 | 0.1% | 1 | | | Irregular flap margin | 1/358 | 0.3% | 1/714 | 0.1% | 1 | | | Loss of BCDVA | 1/358 | 0.3% | 1/714 | 0.1% | 1 | | | Metallic foreign body | 1/358 | 0.3% | 1/714 | 0.1% | 1 | | | **Serious Adverse Events** | | | | | | | | Melting of the flap | 1/358 | 0.3% | 1/714 | 0.1% | 1 | | | Retinal detachment | 1/358 | 0.3% | 1/714 | 0.1% | 1 | | | Seizure | 1/358 | 0.3% | 1/714 | 0.1% | 1 | | | **Secondary Surgical Interventions** | | | | | | | MEL90 P060004/S006 Page 28 {28} # SUMMARY OF SAFETY AND EFFECTIVENESS DATA | Adverse Events | Subjects with 1 or More AE | | Eyes with 1 or More AE | | Events | | | --- | --- | --- | --- | --- | --- | --- | | | n/N | % | n/N | % | % | # | | Epithelial ingrowth removal | 1/358 | 0.3% | 1/714 | 0.1% | 0.1% | 1 | | Retreatment | 1/358 | 0.3% | 1/714 | 0.1% | 0.1% | 1 | | Scleral buckle | 1/358 | 0.3% | 1/714 | 0.1% | 0.1% | 1 | AEs are sorted by descending frequency of events. Note: Of 418 Subjects enrolled, 417 were assigned to cohorts, and 358 treated, 19 had OD and OS assigned to a different cohort (8 were assigned to myopia and mixed astigmatism and 11 to hyperopia and mixed astigmatism). Therefore, the number of subjects in tables of the 3 cohorts will sum to more than the number of subjects in the overall table. **Table 7.1. Adverse Events (AEs) for All Myopic Eyes** | Adverse Events | Subjects with 1 or More AE | | Eyes with 1 or More AE | | Events # | | --- | --- | --- | --- | --- | --- | | | n/N | % | n/N | % | | | One or More of Any Adverse Event | 32/183 | 17.5% | 46/358 | 12.8% | 58 | | **Intraoperative Adverse Events** | | | | | | | Interface debris | 9/183 | 4.9% | 13/358 | 3.6% | 14 | | Procedure interruption due to seizure | 1/183 | 0.5% | 2/358 | 0.6% | 2 | | **Postoperative Adverse Events** | | | | | | | Diffuse lamellar keratitis (Grade 2 or less) | 6/183 | 3.3% | 6/358 | 1.7% | 6 | | Clinical signs and subjective symptoms reported by the patient consistent with dry eye | 5/183 | 2.7% | 6/358 | 1.7% | 9 | | Corneal striae | 3/183 | 1.6% | 4/358 | 1.1% | 4 | | Epithelium in the interface | 3/183 | 1.6% | 4/358 | 1.1% | 4 | | Corneal abrasion | 2/183 | 1.1% | 2/358 | 0.6% | 2 | | Conjunctivitis, allergic | 1/183 | 0.5% | 2/358 | 0.6% | 2 | | Corneal edema between 1 week and 1 month after the procedure | 1/183 | 0.5% | 2/358 | 0.6% | 2 | | Posterior Vitreous Detachment (PVD) | 1/183 | 0.5% | 2/358 | 0.6% | 2 | | Vitreous syneresis | 1/183 | 0.5% | 2/358 | 0.6% | 2 | | Anterior uveitis | 1/183 | 0.5% | 1/358 | 0.3% | 1 | | Corneal edema at 1 month or later | 1/183 | 0.5% | 1/358 | 0.3% | 1 | | Decrease in BCDVA ≥ 10 letters not due to irregular astigmatism at ≥ 3 months | 1/183 | 0.5% | 1/358 | 0.3% | 1 | | Epithelial defect | 1/183 | 0.5% | 1/358 | 0.3% | 1 | | Irregular flap margin | 1/183 | 0.5% | 1/358 | 0.3% | 1 | | Loss of BCDVA | 1/183 | 0.5% | 1/358 | 0.3% | 1 | | **Serious Adverse Events** | | | | | | | Retinal detachment | 1/183 | 0.5% | 1/358 | 0.3% | 1 | | Seizure | 1/183 | 0.5% | 1/358 | 0.3% | 1 | | **Secondary Surgical Interventions** | | | | | | | Scleral buckle | 1/183 | 0.5% | 1/358 | 0.3% | 1 | AEs are sorted by descending frequency of events. Note: Of 418 Subjects enrolled, 417 were assigned to cohorts, and 358 treated, 19 had OD and OS assigned to a different cohort (8 were assigned to myopia and mixed astigmatism and 11 to hyperopia and mixed astigmatism). Therefore, the number of subjects in tables of the 3 cohorts will sum to more than the number of subjects in the overall table. MEL90 P060004/S006 Page 29 {29} SUMMARY OF SAFETY AND EFFECTIVENESS DATA **Table 7.2. Adverse Events (AEs) for All Hyperopic Eyes** | | Subjects with 1 or More AE | | Eyes with 1 or More AE | | Events | | --- | --- | --- | --- | --- | --- | | | n/N | % | n/N | % | # | | **Adverse Events** | | | | | | | One or More of Any Adverse Event | 16/117 | 13.7% | 23/221 | 10.4% | 32 | | **Intraoperative Adverse Events** | | | | | | | Flap tear | 1/117 | 0.9% | 1/221 | 0.5% | 1 | | Free cap | 1/117 | 0.9% | 1/221 | 0.5% | 1 | | Hinge tissue ablated | 1/117 | 0.9% | 1/221 | 0.5% | 1 | | Interface debris | 1/117 | 0.9% | 1/221 | 0.5% | 1 | | **Postoperative Adverse Events** | | | | | | | Clinical signs and subjective symptoms reported by the patient consistent with dry eye | 5/117 | 4.3% | 9/221 | 4.1% | 9 | | Epithelium in the interface | 3/117 | 2.6% | 4/221 | 1.8% | 5 | | Conjunctivitis, viral | 1/117 | 0.9% | 2/221 | 0.9% | 2 | | Epithelium in the interface with loss of 10 letters or more of BCDVA | 1/117 | 0.9% | 1/221 | 0.5% | 2 | | Transient light sensitivity syndrome (TLSS) | 1/117 | 0.9% | 2/221 | 0.9% | 2 | | Chemical splash in eye | 1/117 | 0.9% | 1/221 | 0.5% | 1 | | Conjunctival laceration | 1/117 | 0.9% | 1/221 | 0.5% | 1 | | Conjunctivitis, allergic | 1/117 | 0.9% | 1/221 | 0.5% | 1 | | Corneal abrasion | 1/117 | 0.9% | 1/221 | 0.5% | 1 | | Foreign body sensation | 1/117 | 0.9% | 1/221 | 0.5% | 1 | | Metallic foreign body | 1/117 | 0.9% | 1/221 | 0.5% | 1 | | **Serious Adverse Events** | | | | | | | Melting of the flap | 1/117 | 0.9% | 1/221 | 0.5% | 1 | | **Secondary Surgical Interventions** | | | | | | | Epithelial ingrowth removal | 1/117 | 0.9% | 1/221 | 0.5% | 1 | AEs are sorted by descending frequency of events. Note: Of 418 Subjects enrolled, 417 were assigned to cohorts, and 358 treated, 19 had OD and OS assigned to a different cohort (8 were assigned to myopia and mixed astigmatism and 11 to hyperopia and mixed astigmatism). Therefore, the number of subjects in tables of the 3 cohorts will sum to more than the number of subjects in the overall table. MEL90 P060004/S006 Page 30 {30} SUMMARY OF SAFETY AND EFFECTIVENESS DATA **Table 7.3.** Adverse Events (AEs) for All Mixed Astigmatism Eyes | | Subjects with 1 or More AE | | Eyes with 1 or More AE | | Events | | --- | --- | --- | --- | --- | --- | | | n/N | % | n/N | % | # | | **Adverse Events** | | | | | | | One or More of Any Adverse Event | 11/77 | 14.3% | 15/135 | 11.1% | 16 | | **Intraoperative Adverse Events** | | | | | | | Flap is not of the size and shape as initially intended | 1/77 | 1.3% | 1/135 | 0.7% | 1 | | Flap misaligned | 1/77 | 1.3% | 1/135 | 0.7% | 1 | | Treatment was on wrong Axis for OS | 1/77 | 1.3% | 1/135 | 0.7% | 1 | | **Postoperative Adverse Events** | | | | | | | Clinical signs and subjective symptoms reported by the patient consistent with dry eye | 3/77 | 3.9% | 5/135 | 3.7% | 5 | | Corneal edema between 1 week and 1 month after the procedure | 1/77 | 1.3% | 2/135 | 1.5% | 2 | | MGD (Meibomian Gland Dysfunction) | 1/77 | 1.3% | 2/135 | 1.5% | 2 | | Corneal dryness | 1/77 | 1.3% | 1/135 | 0.7% | 1 | | Foreign body | 1/77 | 1.3% | 1/135 | 0.7% | 1 | | IOP increase of > 10 mmHg above baseline on 2 consec. exams or IOP > 30 mmHg on 2 consec. exams | 1/77 | 1.3% | 1/135 | 0.7% | 1 | | **Secondary Surgical Interventions** | | | | | | | Retreatment | 1/77 | 1.3% | 1/135 | 0.7% | 1 | AEs are sorted by descending frequency of events. Note: Of 418 Subjects enrolled, 417 were assigned to cohorts, and 358 treated, 19 had OD and OS assigned to a different cohort (8 were assigned to myopia and mixed astigmatism and 11 to hyperopia and mixed astigmatism). Therefore, the number of subjects in tables of the 3 cohorts will sum to more than the number of subjects in the overall table. ### **Patient Reported Outcomes for Symptoms** The Patient Reported Outcomes (PRO) instrument used in the IDE clinical study consisted of the Patient Reported Outcomes with LASIK (PROWL) questionnaire with accompanying photographs, and 2 of the 3 domains of the OSDI. Study subjects self-administered the PRO instrument directly to reduce the potential for bias from an interviewer. Results from the PROWL questionnaire are summarized in **Table 8** and results stratified by treatment cohort are presented in **Table 8.1**. A greater proportion of subjects experienced resolution of a symptom or symptoms postoperatively than the proportion of subjects who developed symptoms postoperatively. Similarly, the report of “very” or “extreme” difficulty or bothersomeness with symptoms decreased postoperatively. MEL90 P060004/S006 Page 31 {31} SUMMARY OF SAFETY AND EFFECTIVENESS DATA **Table 8. PROWL Visual Symptoms for All Subjects in Safety Population** | Symptom Information | PreOp n/N (%) | Month 3 n/N (%) | Month 6 n/N (%) | Month 9 n/N (%) | n/N (%) | | --- | --- | --- | --- | --- | --- | | **Symptom Prevalence^{1}** | | | | | | | Any type of symptom | 252/358 (70.4%) | 164/341 (48.1%) | 140/341 (41.1%) | 120/331 (36.3%) | 130/338 (38.5%) | | Double images | 117/358 (32.7%) | 17/341 (5.0%) | 28/341 (8.2%) | 17/331 (5.1%) | 18/338 (5.3%) | | Glare | 140/358 (39.1%) | 56/341 (16.4%) | 47/341 (13.8%) | 38/331 (11.5%) | 46/338 (13.6%) | | Halos | 156/358 (43.6%) | 101/341 (29.6%) | 84/341 (24.6%) | 74/331 (22.4%) | 79/338 (23.4%) | | Starbursts | 200/358 (55.9%) | 134/341 (39.3%) | 114/341 (33.4%) | 101/331 (30.5%) | 107/338 (31.7%) | | **Symptom Development^{1,2}** | | | | | | | Any type of symptom | | 74/288 (25.7%) | 65/289 (22.5%) | 52/281 (18.5%) | 56/286 (19.6%) | | Double images | | 6/229 (2.6%) | 10/231 (4.3%) | 6/228 (2.6%) | 3/230 (1.3%) | | Glare | | 20/208 (9.6%) | 17/210 (8.1%) | 14/203 (6.9%) | 16/206 (7.8%) | | Halos | | 42/193 (21.8%) | 36/195 (18.5%) | 26/187 (13.9%) | 29/189 (15.3%) | | Starbursts | | 43/151 (28.5%) | 29/149 (19.5%) | 31/147 (21.1%) | 32/148 (21.6%) | | **Symptom Resolution** | | | | | | | Any type of symptom | | 201/240 (83.8%) | 196/238 (82.4%) | 195/230 (84.8%) | 199/237 (84.0%) | | Double images | | 101/112 (90.2%) | 92/110 (83.6%) | 92/103 (89.3%) | 93/108 (86.1%) | |…