VIEWPOINT CK SYSTEM

{0} # SUMMARY OF SAFETY AND EFFECTIVENESS DATA FOR A SUPPLEMENTAL PREMARKET APPROVAL APPLICATION # I. GENERAL INFORMATION Device Generic Name: RF Electrosurgical Device Device Trade Name: ViewPoint™ CK System Applicant's Name and Address: Refractec, Inc. 5 Jenner, Suite 150 Irvine, California 92618 USA (949) 784-2600 (949) 784-2601 (fax) Date of Panel Recommendation: February 6, 2004 PMA Number: P010018/S5 Date of Notice of Approval to Applicant: The Refractec, Inc. ViewPoint™ CK System / Conductive Keratoplasty® (CK®) procedure was approved on April 11, 2002 under P010018 for the indication of the temporary reduction of spherical hyperopia in patients who have 0.75 to 3.25 D of cycloplegic spherical hyperopia, less than or equal to 0.75 D of refractive astigmatism (minus cylinder format), a cycloplegic spherical equivalent of 0.75 to 3.00 D, and are 40 years of age or greater with a documented stability of refraction for the prior 12 months, as demonstrated by a change of less than 0.50 D in spherical and cylindrical components of the manifest refraction. The magnitude of correction with this treatment diminishes over time, with some patients retaining some or all of their intended refractive correction. The sponsor submitted this supplement to further expand the clinical indications. The updated clinical data to support this indication are provided in this summary. The pre-clinical test results were presented in the original PMA application. For more information on the data that supported the approved indication, the summary of safety and effectiveness data (SSED) for the original PMA should be referenced. Written requests for copies of the SSED can be obtained from Dockets Management Branch (HFA-305), Food and Drug Administration, 5630 Fishers Lane, rm. 1061, Rockville, MD 20857 under Docket #02M-0174 (P010018) or you may download the file from the internet site http://www.fda.gov/cdrh/pdf/p010018.html. 10 P010018/S5 SSED 1 {1} ## II. INDICATIONS FOR USE The Viewpoint CK System is indicated for the temporary induction of myopia (-1.00 D to -2.00 D) to improve near vision in the non-dominant eye of presbyopic hyperopes or presbyopic emmetropes, via spherical hyperopic treatment of 1.00 to 2.25 D, in patients: 40 years of age or greater; - with a documented stability of refraction for the prior 12 months, as demonstrated by a change of \(< 0.50\mathrm{D}\) in spherical and cylindrical components of the manifest refraction; with \(\leq 0.75\) D of cycloplegic refractive cylinder; and - with a successful preoperative trial of monovision or history of monovision wear (i.e., dominant eye corrected for distance vision and non-dominant eye corrected for near vision). ### III. CONTRAINDICATIONS The Refractec ViewPoint™ CK System / Conductive Keratoplasty® (CK®) procedure should not be used in: Patients who are pregnant or lactating. Patients with keratoconus or other ectatic diseases. - Patients who have diabetes, diagnosed autoimmune disease, connective tissue disease, or clinically significant atopic syndrome. - Patients who are being treated with chronic systemic corticosteroid or other immunosuppressive therapy that may affect wound healing, and any immunocompromised patients. - Patients with implantable electrical devices (pacemakers, defibrillators, cochlear implants, etc). - Patients with nystagmus or other condition that prevents a steady gaze, which is required during surgery. ### IV. WARNINGS AND PRECAUTIONS The warnings and precautions can be found in the device labeling. P010018/S5 SSED 2 11 {2} # V. DEVICE DESCRIPTION The ViewPoint™ CK System is an instrument designed to perform Conductive Keratoplasty® (CK®). CK® is an approved procedure for the temporary spherical treatment for patients with previously untreated hyperopia (farsightedness) between 0.75 and 3.00 diopters. CK® can also be used for the temporary induction of myopia (-1.00 D to -2.00 D) in the non-dominant eye to improve near vision (monovision) in presbyopic hyperopes or presbyopic emmetropes. CK® is performed utilizing the ViewPoint™ CK System to create monovision. Conductive Keratoplasty® utilizes low energy, delivered directly into the corneal stroma through a handpiece and Keratoplast™ Tip, to effect refractive change in the cornea. As a result of conducting a controlled amount of radiofrequency (RF) energy into the corneal stroma, the desired collagen shrinkage temperature is achieved. The peripheral application of this treatment, in a predetermined pattern, creates a band of tightening and results in a steepening of the central cornea. This steepening results in the desired refractive effect. # Overview of the ViewPoint™ CK System The ViewPoint™ CK System used to perform the CK® procedure consists of the following components: Radiofrequency energy-generating console Reusable corneal marker Reusable lid speculum with cable and connector Reusable hand-held, pen-shaped handpiece with cable and connector Instrument holder Power cable - Footpedal Disposable Keratoplast™ Tip - Patient treatment card Refractec submitted declarations that the ViewPoint™ CK System conforms to the following standards: ISO/EN 60601-1 Electrical Safety ISO/EN 60601-1-2 EMC ISO/EN 60601-2-2 Electrical Safety For RF ISO/EN 60601-1-4 Programmable Electrical Medical Systems ISO 10993 Biocompatibility ISO 10993-7 ETO Residuals ISO 11135 ETO Sterilization P010018/S5 SSED 3 12 {3} # ViewPoint™ CK System Console A patient treatment card is inserted into the console to activate the system. The energy level is set at 60% power (0.6W) with a treatment time of 0.6 seconds. An AC powered, portable, low power, energy source provides regulated radiofrequency energy through the handpiece to the Keratoplast™ Tip. # Handpiece The handpiece is a small hand-held, pen-shaped reusable Titanium instrument attached by a removable cable and connector to the console. The radiofrequency energy is delivered by means of the Keratoplast™ Tip, which attaches to the handpiece. # Keratoplast™ Tip A sterile, disposable, stainless steel, Keratoplast™ Tip, 90 microns in diameter and 450 microns long, that delivers radiofrequency energy directly to the corneal stroma, is attached to the handpiece. The Keratoplast™ Tip has a proximal bend of 45° and a distal bend of 90° to allow access to the cornea over the patient's brow and nasal regions. A plastic stop at the very distal portion of the stainless steel tip assures correct depth of penetration. The Keratoplast™ Tip must not be used on fellow eyes or subsequent patients. # Lid Speculum The lid speculum serves as the return (dispersive) electrode for the radiofrequency energy being delivered through the Keratoplast™ Tip. Three types of specula are offered: Barraquer, Cook, and Lancaster. The Barraquer is a small, malleable wire-speculum; the Cook is a small locking speculum; and the Lancaster is a large locking speculum. The Lancaster and Cook lid specula were not used in the clinical investigation of the device. # Footpedal The footpedal attaches to the console and controls the release of radiofrequency energy. # Patient Treatment Card A patient treatment card is inserted into the console to activate the system. # Safety Features The ViewPoint™ CK System has numerous safety features to assure proper operation. The ViewPoint™ CK System includes safety checks at start-up and monitors output during treatment. P010018/S5 SSED 4 13 {4} # *Software* The ViewPoint™ CK System software controls the user interface, and provides the user with system diagnostics and information codes in the event of a device anomaly. Additionally, the software saves all information codes on to the patient treatment card to assist in the diagnosis of technical issues. # VI. ALTERNATIVE PRACTICES OR PROCEDURES Alternative methods of improving near vision include: reading glasses, bifocal eyeglasses, multifocal contact lenses, and monovision contact lens wear. # VII. MARKETING HISTORY The ViewPoint™ CK System has been commercially distributed in 23 countries (Argentina, Australia, Belgium, Brazil, China, Finland, France, Germany, Greece, Hong Kong, Italy, Korea, Mexico, Netherlands, Paraguay, Spain, Saudi Arabia, South Africa, Switzerland, Taiwan, UAE, and the United Kingdom). The ViewPoint™ CK System has not been withdrawn from any country or market for reasons of safety or effectiveness of the device. # VIII. POTENTIAL ADVERSE EVENTS OF THE DEVICE ON HEALTH Potential adverse events associated with the CK® procedure include: decrease in BCVA of > 10 letters not due to irregular astigmatism as shown by hard contact lens refraction at 6 months or later, IOP > 25 mmHg, secondary surgical intervention other than CK® treatment, late onset of haze beyond 6 months with loss of 2 lines (10 letters) or more BCVA, a corneal epithelial defect involving the treatment site, corneal edema, corneal microbial infection, corneal decompensation, corneal scar in the visual axis, intraocular infection, hypopyon, hyphema, onset of cataract unrelated to age/systemic disease/ trauma, retinal detachment, retinal vascular accidents. Please refer to the complete listings of adverse events and complications observed during the clinical study, which are presented in the clinical study section. # IX. SUMMARY OF PRECLINICAL STUDIES Please refer to the SSED of the original PMA P010018. P010018/S5 SSED 5 14 {5} # X. SUMMARY OF CLINICAL STUDIES Refractec, Inc. conducted a clinical study of the ViewPoint™ CK System for the improvement of near vision at five U.S. clinical sites under the auspices of an Investigational Device Exemption (IDE) G980224. The data from this study served as the basis for the approval decision. Safety and effectiveness outcomes through 12 months post-treatment were evaluated for confirmation. # A. Objectives The primary objective of the study was to evaluate the safety and effectiveness of the ViewPoint™ CK System used to improve near vision in presbyopic emmetropes and hyperopes with the Conductive Keratoplasty (CK®) procedure. # B. Study Design This study was a prospective, multi-center clinical study where the primary control was the preoperative status of the treated eye. # 1. Inclusion and Exclusion Criteria Enrollment in the clinical study was limited to patients who: - Required a presbyopic add of +1.00 to +2.00 D, with either a documented history of successful contact lens monovision or successful completion of contact lens monovision trial. - Had +2.00 D to plano (+0.50 to -0.50 D) cycloplegic spherical equivalent, with ≤ 0.75 D refractive cycloplegic astigmatism (cylinder). - Discontinued using hard or rigid gas permeable contact lenses for at least 3 weeks and discontinued using soft contact lenses for at least 2 weeks prior to the preoperative evaluation in the eye to be treated. - Had an average peripheral pachymetry reading of at least 560 microns. - For hard contact lens wearers – had 2 central keratometry readings and 2 manifest refractions taken at least one week apart, the last of which did not differ from the previous values by more than 0.50 D in either meridian; mires were regular in the eye to be treated. - Had distance visual acuity correctable to at least 20/40 in both eyes and near visual acuity correctable to at least J3 in the non-dominant eye. - Were at least 40 years of age. - Were willing and able to return for scheduled follow-up examinations for 24 months after surgery. - Provided written informed consent. Patients with the following conditions were excluded from the study: - Spherical equivalent manifest refraction and spherical equivalent cycloplegic refraction with a difference of more than 0.50 D. - Previous strabismus surgery, or who would have been likely to develop strabismus following the CK® procedure. P010018/S5 SSED 6 15 {6} - Anterior segment pathology, including cataracts (in the operative eye). - Any corneal abnormality or uncontrolled eyelid disease (in the operative eye). - Ophthalmoscopic signs of progressive or unstable refractive error (in the operative eye). Distorted or unclear corneal mires. - Blind in the fellow eye. Previous intraocular or corneal surgery. History of herpes zoster or herpes simplex keratitis. History of steroid-responsive rise in IOP, glaucoma, or preoperative \(\mathrm{IOP} > 21\mathrm{mmHg}\) - At risk for angle closure or with a potentially occludable angle. - Diabetes, diagnosed autoimmune disease, connective tissue disease, or clinically significant atopic syndrome. - Chronic systemic corticosteroid or other immunosuppressive therapy, and any immunocompromised patients. - Using ophthalmic medication(s) other than artificial tears for treatment of any ocular pathology. - Using systemic medications with significant ocular side effects. History of keloid formation. - Intractable keratoconjunctivitis sicca. - Pregnant, planning to be pregnant, or lactating during the course of the study. - Known sensitivity to planned study concomitant medications. - Participating in any other ophthalmic drug or device clinical trial during the time of this clinical investigation. # 2. Study Endpoints The following primary study parameters were evaluated in the determination of safety and effectiveness of the ViewPoint™ CK System for hyperopic and emmetropic eyes treated for near. # Primary Safety Parameter: - Preservation of best corrected distance visual acuity: less than 5% of eyes were to lose more than 2 lines of best corrected distance visual acuity at the postoperative interval at which stability has been established. # Primary Effectiveness Parameter: - Predictability: 75% of eyes were to have a manifest refraction spherical equivalent within ± 1.00 D of the attempted correction at the postoperative interval at which stability has been established. The following secondary study parameters were evaluated in the determination of safety and effectiveness of the ViewPoint™ CK System for hyperopic and emmetropic eyes treated for near. P010018/S5 SSED 7 16 {7} # Secondary Safety Parameters: - Preservation of best corrected near visual acuity: less than \(5\%\) of eyes were to lose more than 2 lines of best corrected near visual acuity at the postoperative interval at which stability has been established. - Preservation of best corrected distance and near visual acuity: less than \(1\%\) of eyes with preoperative BCVA of 20/20 were to have distance and near visual acuity worse than 20/40 BCVA at the postoperative interval at which stability has been established. - Mean extent of induced manifest refractive astigmatism: less than \(5\%\) of eyes were to have postoperative manifest refractive astigmatism that increased from baseline by greater than 2.00 D at the postoperative interval at which stability has been established. - Results of slit lamp examination: less than \(1\%\) of eyes were to have clinically significant haze, defined as a decrease in BCVA of \(>2\) lines not due to irregular astigmatism, at the postoperative interval at which stability has been established. - Cumulative incidence of adverse events: adverse events were to occur in less than \(5\%\) of eyes and any single adverse event should occur in less than \(1\%\) of eyes. # Secondary Effectiveness Parameters: - Predictability: \(50\%\) of eyes were to have a manifest refraction spherical equivalent within \(\pm 0.50\) D of the attempted correction at the postoperative interval at which stability has been established. - Stability (absence of change in refractive outcome over time): \(95\%\) of eyes were to have a change of \(\leq 1.00\) D in manifest refraction spherical equivalent between two refractions performed at least three months apart. - Improvement in distance uncorrected visual acuity: \(85\%\) of eyes who had 20/20 or better spectacle-corrected visual acuity preoperatively, were to have uncorrected visual acuity of 20/40 or better at the postoperative interval at which stability has been established. For those eyes which had spectacle-corrected visual acuity of worse than 20/20 but at least 20/40 preoperatively, \(75\%\) were to have uncorrected visual acuity of 20/40 or better at the postoperative interval at which stability has been established. - Improvement in near uncorrected visual acuity: \(75\%\) of eyes that had a full correction were to have uncorrected near visual acuity of J3 or better. - Subject satisfaction as measured by subjective questionnaires. P010018/S5 SSED 8 17 {8} # C. Study Plan and Subject Assessments # 1. Study Plan All subjects were expected to return for follow-up examinations at 1 day, 7 days, and 1, 3, 6, 9, 12, and 24 months post-treatment. CK retreatments were allowed per the study protocol for up to a maximum of 32 spots. # 2. Subject Assessments and Efficacy Criteria - Monocular and binocular near visual acuity, uncorrected and best spectacle-corrected - Monocular and binocular distance visual acuity, uncorrected and best spectacle-corrected Manifest refraction Cycloplegic refraction - Pachymetry (preoperative) Intraocular pressure - Slit lamp examination - Mesopic and photopic contrast sensitivity, with and without glare (subgroup) - Computerized corneal topography (postoperatively in eyes with anomalous refractive outcomes) Central keratometry - Subject self-evaluation/questionnaire - Subject spectacle dependence evaluation/questionnaire # D. Study Period and Investigational Sites Subjects were treated between May 15, 2001 and January 7, 2003 at 5 investigational sites. The database for this PMA supplement cohort reflects data collected through July 21, 2003 and includes 188 eyes of 150 subjects: 150 primary eyes treated for near and 38 fellow eyes treated for distance. P010018/S5 SSED 9 18 {9} # E. Demographic Data As presented in Table 1 below, of the 150 subjects enrolled, 61% were female and 39% were male. The mean age for all enrolled subjects was 52.9 years, with a range from 43.7 to 70.8 years. The study population consisted primarily of Caucasians (96%). The mean intended correction for near eyes was 2.03 D. Table 1 Demographics | | Near Eyes | | Distance Eyes | | All Eyes | | | | --- | --- | --- | --- | --- | --- | --- | --- | | | | 150 Eyes of 150 Subjects | | 38 Eyes of 38 Subjects | | 188 Eyes of 150 Subjects | | | Gender | Male | 58 | 39% | 13 | 34% | 58 | 39% | | | Female | 92 | 61% | 25 | 66% | 92 | 61% | | Race | Caucasian | 144 | 96% | 37 | 97% | 144 | 96% | | | Black | 1 | 1% | 0 | 0% | 1 | 1% | | | Asian | 1 | 1% | 1 | 3% | 1 | 1% | | | Other | 4 | 3% | 0 | 0% | 4 | 3% | | Eye | Left | 83 | 55% | 16 | 42% | 99 | 53% | | | Right | 67 | 45% | 22 | 58% | 89 | 47% | | Age (yrs) | N | 150 | | 38 | | 150 | | | | Mean | 52.9 | | 54.1 | | 52.9 | | | | Standard Deviation | 4.80 | | 4.77 | | 4.80 | | | | Median | 52.0 | | 53.8 | | 52.0 | | | | Range | 43.7,70.8 | | 43.7,61.3 | | 43.7,70.8 | | | Range of Intended Correction | N | 150 | | 38 | | | | | | Mean | 2.03 | | 1.23 | | | | | | Standard Deviation | 0.625 | | 0.367 | | | | | | Median | 2.00 | | 1.25 | | | | | | Range | 0.75,3.00 | | 0.75,2.00 | | | | | Range of Target | N | 150 | | 38 | | | | | | Mean | -1.47 | | 0.00 | | | | | | Standard Deviation | 0.356 | | 0.000 | | | | | | Median | -1.25 | | 0.00 | | | | | | Range | -2.25,-1.00 | | 0.00,0.00 | | | | BCS-011-PRS Source: /refroctor/prs/sas/dem1_tab.sas Date Generated: 23JUL03 Data Lock: 21JUL2003 P010018/S5 SSED 10 19 {10} # F. Data Analysis and Results # 1. Pre-Treatment Characteristics Table 2 presents a summary of the pre-treatment refraction for near and distance eyes. The treatment goal for near treated eyes was myopia and for distance treated eyes the treatment goal was emmetropia. Table 2 Preoperative Refractive Parameters | | | Near Eyes | | Distance Eyes | | | --- | --- | --- | --- | --- | --- | | Spherical Equivalent (MRSE) * | -0.50 to -0.125 D | 19 | 13% | 0 | 0% | | | 0.0-0.99 D | 99 | 66% | 12 | 32% | | | 1.0-2.00 D | 32 | 21% | 26 | 68% | | | Total | 150 | 100% | 38 | 100% | | Cylinder (manifest) | 0.00 D | 53 | 35% | 10 | 26% | | | -0.25 D | 27 | 18% | 7 | 18% | | | -0.50 D | 45 | 30% | 18 | 47% | | | -0.75 D | 25 | 17% | 3 | 8% | | | -1.00 D | 0 | 0% | 0 | 0% | | | Total | 150 | 100% | 38 | 100% | | Spherical Equivalent (CRSE) * | -0.50 to -0.125 D | 17 | 11% | 0 | 0% | | | 0.0-0.99 D | 92 | 61% | 9 | 24% | | | 1.0-2.00 D | 41 | 27% | 29 | 76% | | | Total | 150 | 100% | 38 | 100% | | Cylinder (cycloplegic) | 0.00 D | 52 | 35% | 11 | 29% | | | -0.25 D | 30 | 20% | 7 | 18% | | | -0.50 D | 41 | 27% | 15 | 39% | | | -0.75 D | 27 | 18% | 4 | 11% | | | -1.00 D | 0 | 0% | 1 | 3% | | | Total | 150 | 100% | 38 | 100% | * Per study inclusion criteria, emmetropes desiring near correction were enrolled with plano (defined as -0.50 to +0.50 D) One ineligible subject was enrolled with -0.75 D preoperative CRSE. RCS-011-PRS Source: refractive pres test pre tab sas Date Generated: 23JUL03 Data Lock: 21JUL2003 P010018/S5 SSED 11 20 {11} ## 2. Subject Accountability Of the 150 near eyes enrolled in the study, follow-up data through 6 months postoperative are available for 146 eyes (97%), as shown in Table 3. Of the remaining eyes at 6 months, one (<1%) was discontinued from the study due to retreatment with surface ablation, one (<1%) was discontinued for CK retreatment and re-enrolled and four (3%) missed their scheduled 6 month postoperative visit. Table 3 Accountability Eyes Treated for Near | | Month 1 | | Month 3 | | Month 6 | | Month 9 | | Month 12 | | | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | | Available for Analysis | 145/150 | 97% | 148/150 | 99% | 146/150 | 97% | 94/150 | 63% | 77/150 | 51% | | Discontinued* | 0/150 | 0% | 0/150 | 0% | 2/150 | 1% | 4/150 | 3% | 9/150 | 6% | | Missed Visit | 5/150 | 3% | 2/150 | 1% | 4/150 | 3% | 3/150 | 2% | 3/150 | 2% | | Not yet eligible for interval | 0/150 | 0% | 0/150 | 0% | 0/150 | 0% | 53/150 | 35% | 70/150 | 47% | | Lost to Follow-up | 0/150 | 0% | 0/150 | 0% | 0/150 | 0% | 0/150 | 0% | 1/150 | 1% | | Accountability | 145/150 | 97% | 148/150 | 99% | 146/150 | 97% | 94/97 | 97% | 77/80 | 96% | * 1 eye discontinued due to inability of patient to continue in study; 1 eye discontinued due to an adverse event (multiple sclerosis); 1 eye discontinued for retreatment with PRK; 12 eyes discontinued for CK retreatment as per study protocol. See Table 16.2. RCS-011-PRS Source: refractoc pres vas acct tab.xos Date Generated: 23JUL03 Data Lock: 21JUL2003 P010018/S5 SSED 12 21 {12} ### 3. Summary of Key Effectiveness Variables Tables 4 demonstrates that the key effectiveness outcomes at 6 months postoperative meet or exceed the outcomes recommended in the October 10, 1996 FDA Guidance for Refractive Surgery Lasers. The clinical trial included eyes within a treatment range of +0.75 to 3.00 D. The final approved indication limited the treatment range to +1.00 to 2.25 D. The other eyes treated reported adequate safety but demonstrated an efficacy, which was significantly below that for the approved indication. Table 4 Summary of Key Efficacy Variables Eyes Treated for Near with Intended Correction of 1.00 to 2.25 D | | Month 1 | | Month 3 | | Month 6 | | Month 9 | | Month 12 | | | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | | Efficacy Variables -- Eyes Treated for Near (Full Correction)* | | | | | | | | | | | | UCVA-N J1+ or better | 22/78 | 28% | 20/81 | 25% | 19/81 | 23% | 16/64 | 25% | 7/53 | 13% | | UCVA-N J1 or better | 46/78 | 59% | 44/81 | 54% | 41/81 | 51% | 31/64 | 48% | 20/53 | 38% | | UCVA-N J2 or better | 64/78 | 82% | 62/81 | 77% | 59/81 | 73% | 48/64 | 75% | 37/53 | 70% | | UCVA-N J3 or better | 71/78 | 91% | 71/81 | 88% | 67/81 | 83% | 54/64 | 84% | 43/53 | 81% | | UCVA-N J5 or better | 76/78 | 97% | 79/81 | 98% | 76/81 | 94% | 59/64 | 92% | 52/53 | 98% | | UCVA-N J7 or better | 78/78 | 100% | 81/81 | 100% | 79/81 | 98% | 62/64 | 97% | 53/53 | 100% | | Efficacy Variables -- Eyes Treated for Near* | | | | | | | | | | | | MRSE ≤ 0.5 D from Target | 55/88 | 63% | 60/91 | 66% | 59/91 | 65% | 50/73 | 68% | 43/62 | 69% | | MRSE ≤ 1.0 D from Target | 79/88 | 90% | 82/91 | 90% | 83/91 | 91% | 66/73 | 90% | 58/62 | 94% | | MRSE ≤ 2.0 D from Target | 88/88 | 100% | 91/91 | 100% | 91/91 | 100% | 73/73 | 100% | 62/62 | 100% | * Efficacy analyses exclude 3 eyes with a target near correction of > -2.00 D, the maximum allowed in the protocol. RCS-011-PRS Source: refractivepres nas ekey_tab.sas Date Generated: 27FEB04 Data Lock: 21JUL2003 P010018/S5 SSED 13 22 {13} Table 5a Summary of Key Efficacy Variables at Month 6, Stratified by Treatment Spots Applied Eyes Treated for Near with Intended Correction of 1.00 to 2.25 D | | 16 Spots | | 24 Spots | | | --- | --- | --- | --- | --- | | | 1.00 - 1.63 D | | 1.75 - 2.25 D | | | Efficacy Variables -- Eyes Treated for Near with Full Correction* | | | | | | UCVA-N J1+ or better | 9/36 | 25% | 10/44 | 23% | | UCVA-N J1 or better | 14/36 | 39% | 26/44 | 59% | | UCVA-N J2 or better | 26/36 | 72% | 32/44 | 73% | | UCVA-N J3 or better | 30/36 | 83% | 36/44 | 82% | | UCVA-N J5 or better | 32/36 | 89% | 43/44 | 98% | | UCVA-N J7 or better | 34/36 | 94% | 44/44 | 100% | | Efficacy Variables -- Eyes Treated for Near* | | | | | | MRSE ≤ 0.5 D from Target | 28/42 | 67% | 31/48 | 65% | | MRSE ≤ 1.0 D from Target | 38/42 | 90% | 44/48 | 92% | | MRSE ≤ 2.0 D from Target | 42/42 | 100% | 48/48 | 100% | * Efficacy analyses exclude 3 eyes with a target near correction of > -2.00 D, the maximum allowed in the protocol. Note: Table excludes 1 eye treated intraoperatively with additional treatment spots for management of induced cylinder. BCS-011-PRS Source: refractive pres sus-ekeys_tab.sas Date Generated: 18FEB04 Data Lock: 21JUL2003 Table 5b Summary of Key Efficacy Variables at Month 12, Stratified by Treatment Spots Applied Eyes Treated for Near with Intended Correction of 1.00 to 2.25 D | | 16 Spots | | 24 Spots | | | --- | --- | --- | --- | --- | | | 1.00 - 1.63 D | | 1.75 - 2.25 D | | | Efficacy Variables -- Eyes Treated for Near with Full Correction* | | | | | | UCVA-N J1+ or better | 6/28 | 21% | 1/25 | 4% | | UCVA-N J1 or better | 13/28 | 46% | 7/25 | 28% | | UCVA-N J2 or better | 22/28 | 79% | 15/25 | 60% | | UCVA-N J3 or better | 25/28 | 89% | 18/25 | 72% | | UCVA-N J5 or better | 28/28 | 100% | 24/25 | 96% | | UCVA-N J7 or better | 28/28 | 100% | 25/25 | 100% | | Efficacy Variables -- Eyes Treated for Near* | | | | | | MRSE ≤ 0.5 D from Target | 28/34 | 82% | 15/28 | 54% | | MRSE ≤ 1.0 D from Target | 33/34 | 97% | 25/28 | 89% | | MRSE ≤ 2.0 D from Target | 34/34 | 100% | 28/28 | 100% | * Efficacy analyses exclude 3 eyes with a target near correction of > -2.00 D, the maximum allowed in the protocol. Note: Table excludes 1 eye treated intraoperatively for induced cylinder. BCS-011-PRS Source: refractive pres sus keys_tab.sas Date Generated: 07MAR04 Data Lock: 21JUL2003 23 P010018/S5 SSED 14 {14} Table 5c Eyes Undercorrected by > 1.00 D, Stratified by Treatment Spots Applied Eyes Treated for Near with Intended Correction of 1.00 to 2.25 D | | 16 Spots 1.00 – 1.63 D | | 24 Spots 1.75 – 2.25 D | | | --- | --- | --- | --- | --- | | 6 Months | 4/42 | 10% | 4/49 | 8% | | 12 Months | 1/34 | 3% | 3/28 | 11% | Table 5d Proportion of Eyes with Near UCVA J3 (20/40) or Better at 6 Months, Stratified by Age and Treatment Spots Applied Eyes Treated for Near with Intended Correction of 1.00 to 2.25 D | | ≤ 50 years | | 50 to < 55 years | | ≥ 55 years | | All Eyes | | | --- | --- | --- | --- | --- | --- | --- | --- | --- | | 16 spots 1.00 – 1.63 D | 11/14 | 79% | 11/12 | 92% | 8/10 | 80% | 30/36 | 83% | | 24 spots 1.75 – 2.25 D | 14/14 | 100% | 16/22 | 73% | 7/9 | 78% | 37/45 | 82% | | All Eyes | 25/28 | 89% | 27/34 | 79% | 15/19 | 79% | | | 24 P010018/S5 SSED 15 {15} The improvement in near vision is accomplished through the application of CK to the non-dominant eye to achieve a myopic endpoint (-1.00 to -2.00 D). Therefore, it is important to assess the impact of intentional anisometropia on binocular vision. Binocular cumulative uncorrected visual acuity at near for eyes treated for a full correction at near is shown in Table 6. Table 6 Binocular Cumulative Uncorrected Visual Acuity - Near All Subjects Treated for Near with Intended Correction of 1.00 to 2.25 D (Full Correction) | | Preop | | Month 1 | | Month 3 | | Month 6 | | Month 9 | | Month 12 | | | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | | UCVA-N J1+ or better | 0/81 | 0% | 29/78 | 37% | 25/81 | 31% | 23/81 | 28% | 18/64 | 28% | 12/53 | 23% | | UCVA-N J1 or better | 1/81 | 1% | 52/78 | 67% | 54/81 | 67% | 45/81 | 56% | 38/64 | 59% | 25/53 | 47% | | UCVA-N J2 or better | 6/81 | 7% | 66/78 | 85% | 63/81 | 78% | 66/81 | 81% | 54/64 | 84% | 41/53 | 77% | | UCVA-N J3 or better | 12/81 | 15% | 73/78 | 94% | 74/81 | 91% | 73/81 | 90% | 58/64 | 91% | 47/53 | 89% | | UCVA-N J5 or better | 30/81 | 37% | 77/78 | 99% | 80/81 | 99% | 78/81 | 96% | 61/64 | 95% | 52/53 | 98% | | UCVA-N J7 or better | 51/81 | 63% | 78/78 | 100% | 81/81 | 100% | 80/81 | 99% | 63/64 | 98% | 53/53 | 100% | | UCVA-N J10 or better | 69/81 | 85% | 78/78 | 100% | 81/81 | 100% | 80/81 | 99% | 64/64 | 100% | 53/53 | 100% | | UCVA-N J16 or better | 80/81 | 99% | 78/78 | 100% | 81/81 | 100% | 81/81 | 100% | 64/64 | 100% | 53/53 | 100% | | Not reported | 0/81 | 0% | 0/78 | 0% | 0/81 | 0% | 0/81 | 0% | 0/64 | 0% | 0/53 | 0% | | Total | 81/81 | 100% | 78/78 | 100% | 81/81 | 100% | 81/81 | 100% | 64/64 | 100% | 53/53 | 100% | Note: Efficacy analyses exclude 3 eyes with a target near correction of > -2.00 D, the maximum allowed in the protocol. RCS-011-PRS Source: refractive pres. nov. womow tab. nov Date Generated: 18/5/2004 Data Lock: 21JUL2003 P010018/S5 SSED 16 25 {16} Binocular cumulative uncorrected visual acuity at distance is shown in Table 7. Table 7 Binocular Cumulative Uncorrected Visual Acuity - Distance All Subjects Treated for Near with Intended Correction of 1.00 to 2.25 D | | Preop | | Month 1 | | Month 3 | | Month 6 | | Month 9 | | Month 12 | | | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | | UCVA-D 20/20 or better | 84/91 | 92% | 85/87 | 98% | 88/91 | 97% | 86/91 | 95% | 72/73 | 99% | 60/62 | 97% | | UCVA-D 20/25 or better | 89/91 | 98% | 87/87 | 100% | 90/91 | 99% | 91/91 | 100% | 73/73 | 100% | 61/62 | 98% | | UCVA-D 20/32 or better | 90/91 | 99% | 87/87 | 100% | 91/91 | 100% | 91/91 | 100% | 73/73 | 100% | 62/62 | 100% | | UCVA-D 20/40 or better | 91/91 | 100% | 87/87 | 100% | 91/91 | 100% | 91/91 | 100% | 73/73 | 100% | 62/62 | 100% | | UCVA-D 20/80 or better | 91/91 | 100% | 87/87 | 100% | 91/91 | 100% | 91/91 | 100% | 73/73 | 100% | 62/62 | 100% | | UCVA-D 20/200 or better | 91/91 | 100% | 87/87 | 100% | 91/91 | 100% | 91/91 | 100% | 73/73 | 100% | 62/62 | 100% | | Not reported | 0/91 | 0% | 1/88 | 1% | 0/91 | 0% | 0/91 | 0% | 0/73 | 0% | 0/62 | 0% | | Total | 91/91 | 100% | 87/87 | 100% | 91/91 | 100% | 91/91 | 100% | 73/73 | 100% | 62/62 | 100% | Note: Efficacy analyses exclude 3 eyes with a target near correction of > -2.00 D, the maximum allowed in the protocol. BCS-011-PRS Source: refractive pres. vas. cuvion tab. var Date Generated: 18/1/2014 Data Lock: 21/1/2013 To ensure that study subjects did not experience an improvement in uncorrected near vision with a concurrent compromise in uncorrected distance acuity, the combination of binocular uncorrected near and distance visual acuity is shown in Table 8. Table 8 Combined Binocular Uncorrected Visual Acuity Distance and Near All Subjects Treated for Near with Intended Correction of 1.00 to 2.25 D (Full Correction) | | Preop | | Month 1 | | Month 3 | | Month 6 | | Month 9 | | Month 12 | | | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | | 20/20 or better and J1 or better | 1/81 | 1% | 50/77 | 65% | 51/81 | 63% | 41/81 | 51% | 38/64 | 59% | 24/53 | 45% | | 20/25 or better and J2 or better | 6/81 | 7% | 65/77 | 84% | 62/81 | 77% | 66/81 | 81% | 54/64 | 84% | 41/53 | 77% | | 20/32 or better and J3 or better | 12/81 | 15% | 72/77 | 94% | 74/81 | 91% | 73/81 | 90% | 58/64 | 91% | 47/53 | 89% | | 20/40 or better and J3 or better | 12/81 | 15% | 72/77 | 94% | 74/81 | 91% | 73/81 | 90% | 58/64 | 91% | 47/53 | 89% | | Not reported | 0/81 | 0% | 1/78 | 1% | 0/81 | 0% | 0/81 | 0% | 0/64 | 0% | 0/53 | 0% | | Total | 81/81 | 100% | 77/77 | 100% | 81/81 | 100% | 81/81 | 100% | 64/64 | 100% | 53/53 | 100% | Note: Efficacy analyses exclude 3 eyes with a target near correction of > -2.00 D, the maximum allowed in the protocol. BCS-011-PRS Source: refractive pres. vas. unaudua tab. var Date Generated: 18/1/2014 Data Lock: 21/1/2013 26 P010018/S5 SSED 17 {17} # a. Factors Associated with Outcomes Statistical modeling performed on the data generated in the CK® clinical study found no effect of age, race, sex or clinical site on outcomes. # b. Subject Satisfaction Subjects were asked to rate their quality of vision compared to before the Conductive Keratoplasty® (CK®) procedure. Table 9 shows the percentage of subjects that rated each condition as improvement that was “extreme,” “marked,” “moderate,” “slight,” or “no improvement”. Table 9 Quality of Vision Eyes Treated for Near with Intended Correction of 1.00 to 2.25 D | | Month 1 | | Month 3 | | Month 6 | | Month 9 | | Month 12 | | | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | | Extreme Improvement | 32/89 | 36% | 40/92 | 43% | 40/93 | 43% | 28/74 | 38% | 24/62 | 39% | | Marked Improvement | 36/89 | 40% | 32/92 | 35% | 30/93 | 32% | 23/74 | 31% | 26/62 | 42% | | Moderate Improvement | 13/89 | 15% | 15/92 | 16% | 13/93 | 14% | 17/74 | 23% | 9/62 | 15% | | Slight Improvement | 6/89 | 7% | 4/92 | 4% | 7/93 | 8% | 3/74 | 4% | 2/62 | 3% | | No Improvement | 2/89 | 2% | 1/92 | 1% | 3/93 | 3% | 3/74 | 4% | 1/62 | 2% | | Not Reported | 1/90 | 1% | 1/93 | 1% | 0/93 | 0% | 0/74 | 0% | 1/63 | 2% | | Total | 89/89 | 100% | 92/92 | 100% | 93/93 | 100% | 74/74 | 100% | 62/62 | 100% | RCS-011-PRS Source: /refractec/pres/sav/q_tab.sas Date Generated: 18FEB04 Data Lock: 21JUL2003 P010018/S5 SSED 18 27 {18} Overall subject satisfaction was assessed on a subject survey at 1, 3, 6, 9, and 12 months post-treatment using a 5-point grading scale from "very satisfied" to "very dissatisfied" (Table 10). # Table 10 # Patient Satisfaction # Eyes Treated for Near with Intended Correction of 1.00 to 2.25 D | | Month 1 | | Month 3 | | Month 6 | | Month 9 | | Month 12 | | | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | | Very Satisfied | 49/90 | 54% | 54/92 | 59% | 48/93 | 52% | 38/74 | 51% | 35/62 | 56% | | Satisfied | 29/90 | 32% | 25/92 | 27% | 26/93 | 28% | 21/74 | 28% | 17/62 | 27% | | Neutral | 7/90 | 8% | 11/92 | 12% | 16/93 | 17% | 12/74 | 16% | 7/62 | 11% | | Dissatisfied | 5/90 | 6% | 2/92 | 2% | 3/93 | 3% | 3/74 | 4% | 3/62 | 5% | | Very Dissatisfied | 0/90 | 0% | 0/92 | 0% | 0/93 | 0% | 0/74 | 0% | 0/62 | 0% | | Not Reported | 0/90 | 0% | 1/93 | 1% | 0/93 | 0% | 0/74 | 0% | 1/63 | 2% | | Total | 90/90 | 100% | 92/92 | 100% | 93/93 | 100% | 74/74 | 100% | 62/62 | 100% | RCS-011-PRS Source: refractec pres sus sat tab.xls Date Generated: 18FEB04 Data Lock: 21JUL2003 # Table 11 # Quality of Depth Perception # Eyes Treated for Near with Intended Correction of 1.00 to 2.25 D | | Preop* | | Month 1 | | Month 3 | | Month 6 | | Month 9 | | Month 12 | | | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | | Depth Perception* | | | | | | | | | | | | | | Excellent | 15/81 | 19% | 11/90 | 12% | 25/91 | 27% | 22/93 | 24% | 15/73 | 21% | 12/61 | 20% | | Very Good | 30/81 | 37% | 34/90 | 38% | 26/91 | 29% | 39/93 | 42% | 28/73 | 38% | 24/61 | 39% | | Good | 31/81 | 38% | 38/90 | 42% | 34/91 | 37% | 24/93 | 26% | 25/73 | 34% | 21/61 | 34% | | Fair | 4/81 | 5% | 7/90 | 8% | 6/91 | 7% | 6/93 | 6% | 5/73 | 7% | 4/61 | 7% | | Poor | 1/81 | 1% | 0/90 | 0% | 0/91 | 0% | 2/93 | 2% | 0/73 | 0% | 0/61 | 0% | | Not Reported | 13/94 | 14% | 0/90 | 0% | 2/93 | 2% | 0/93 | 0% | 1/74 | 1% | 2/63 | 3% | | Total | 81/81 | 100% | 90/90 | 100% | 91/91 | 100% | 93/93 | 100% | 73/73 | 100% | 61/61 | 100% | * Preoperative depth perception was assessed wearing monovision contact lenses rather than assessing depth perception with both eyes corrected for distance (non-monovision baseline). RCS-011-PRS Source: refractec pres sus vq2 tab.xls Date Generated: 18FEB04 Data Lock: 21JUL2003 28 P010018/S5 SSED 19 {19} The questionnaire used during the study asked a single question regarding use of spectacles or contact lenses for near vision and distance vision, the results of which are shown below in Tables 12 and 13. Table 12 Spectacle Dependence for Near Vision Eyes Treated for Near with Intended Correction of 1.00 to 2.25 D | | Month 1 | | Month 3 | | Month 6 | | Month 9 | | Month 12 | | | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | | Do you wear spectacles or contact lenses for near vision in your treated eye? | 28/90 | 31% | 27/93 | 29% | 36/93 | 39% | 32/74 | 43% | 33/63 | 52% | | All near activities | 3/90 | 3% | 4/93 | 4% | 14/93 | 15% | 12/74 | 16% | 8/63 | 13% | | Working on computer | 13/90 | 14% | 10/93 | 11% | 14/93 | 15% | 16/74 | 22% | 10/63 | 16% | | Reading | 28/90 | 31% | 26/93 | 28% | 34/93 | 37% | 30/74 | 41% | 33/63 | 52% | RCS-011-PRS Source: refroctecpres.sas.wear_tab.sas Date Generated: 18FEB04 Data Lock: 21JUL2003 Table 13 Spectacle Dependence for Distance Vision Eyes Treated for Near with Intended Correction of 1.00 to 2.25 D | | Month 1 | | Month 3 | | Month 6 | | Month 9 | | Month 12 | | | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | | Do you wear spectacles or contact lenses for distance vision in your treated eye? | 0/90 | 0% | 2/93 | 2% | 2/93 | 2% | 3/74 | 4% | 2/63 | 3% | | Whenever driving | 0/90 | 0% | 0/93 | 0% | 1/93 | 1% | 2/74 | 3% | 1/63 | 2% | | Night driving only | 0/90 | 0% | 2/93 | 2% | 2/93 | 2% | 1/74 | 1% | 1/63 | 2% | | Watching TV or movies | 0/90 | 0% | 0/93 | 0% | 0/93 | 0% | 0/74 | 0% | 0/63 | 0% | | Sporting events/activities only | 0/90 | 0% | 0/93 | 0% | 0/93 | 0% | 0/74 | 0% | 1/63 | 2% | | All distance activities (full time) | 0/90 | 0% | 0/93 | 0% | 0/93 | 0% | 0/74 | 0% | 1/63 | 2% | RCS-011-PRS Source: refroctecpres.sas.wear_tab.sas Date Generated: 18FEB04 Data Lock: 21JUL2003 P010018/S5 SSED 20 29 {20} # 4. Change in Manifest Refraction Over Time Table 14a Stability of Manifest Refraction through Month 12 (Eyes with Consecutive Visits) Eyes Treated for Near with Intended Correction of 1.00 to 2.25 D | | Between 1 and 3 Months | | Between 3 and 6 Months | | Between 6 and 9 Months | | Between 9 and 12 Months | | | --- | --- | --- | --- | --- | --- | --- | --- | --- | | Change in MRSE ≤ 0.50 D | 70/88 | 80% | 78/91 | 86% | 72/73 | 99% | 59/62 | 95% | | Change in MRSE ≤ 0.75 D | 80/88 | 91% | 86/91 | 95% | 72/73 | 99% | 60/62 | 97% | | Change in MRSE ≤ 1.00 D | 83/88 | 94% | 91/91 | 100% | 73/73 | 100% | 61/62 | 98% | | Change in MRSE/Month (Paired Differences in D) | | | | | | | | | | Mean | 0.06 | | 0.04 | | 0.04 | | 0.03 | | | 95% Confidence Interval | 0.00,0.12 | | 0.02,0.06 | | 0.02,0.06 | | 0.01,0.05 | | | Standard Deviation | 0.241 | | 0.125 | | 0.081 | | 0.098 | | | Change in MRSE (Paired Differences in D) | | | | | | | | | | Mean | 0.12 | | 0.13 | | 0.11 | | 0.10 | | | 95% Confidence Interval | 0.02,0.22 | | 0.05,0.21 | | 0.05,0.17 | | 0.02,0.18 | | | Standard Deviation | 0.482 | | 0.375 | | 0.243 | | 0.293 | | Note: Efficacy analyses exclude 3 eyes with a target near correction of > -2.00 D, the maximum allowed in the protocol. HCS-011-PRS Source: refractive pres. tax rs1_sub.usa Data Generated: 18/8/2004 Data Lock: 21/8/2003 Table 14b Mean Difference in MRSE* Stratified by Spot Pattern (Consecutive Visits) All Eyes Treated for Near with Intended Correction of 1.00 to 2.25 D | | | Between 1 and 3 Months | Between 3 and 6 Months | Between 6 and 9 Months | Between 9 and 12 Months | | --- | --- | --- | --- | --- | --- | | 16 Spots 1.00 – 1.63 D | N | 40 | 42 | 40 | 34 | | | Mean | 0.05 | 0.06 | 0.01 | 0.02 | | | 95% CI | -0.01, 0.11 | 0.02, 0.10 | -0.01, 0.03 | 0.00, 0.04 | | | SD | 0.191 | 0.111 | 0.075 | 0.068 | | 24 Spots 1.75 – 2.25 D | N | 47 | 48 | 33 | 28 | | | Mean | 0.06 | 0.02 | 0.06 | 0.06 | | | 95% CI | -0.02, 0.14 | -0.02, 0.06 | 0.04, 0.08 | 0.02, 0.10 | | | SD | 0.270 | 0.136 | 0.080 | 0.122 | * The duration of the initial refractive effect is not known. 30 P010018/S5 SSED 21 {21} # Mean MRSE Over Time # Eyes Treated for Near with Intended Correction of 1.00 to 2.25 D  # 5. Summary of Key Safety Variables Table 15 demonstrates that the key safety outcomes meet or exceed the outcomes recommended in the October 10, 1996 FDA Guidance for Refractive Surgery Lasers. Table 15 Summary of Key Safety Variables Eyes Treated for Near with Intended Correction of 1.00 to 2.25 D | | Month 1 | | Month 3 | | Month 6 | | Month 9 | | Month 12 | | | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | | Safety Variables – Eyes Treated for Near | | | | | | | | | | | | Loss of > 2 lines BCVA-D | 2/90 | 2% | 0/93 | 0% | 0/93 | 0% | 0/74 | 0% | 0/63 | 0% | | Loss of ≥ 2 lines BCVA-D | 3/90 | 3% | 1/93 | 1% | 2/93 | 2% | 0/74 | 0% | 0/63 | 0% | | BCVA-D worse than 20/40 | 0/90 | 0% | 0/93 | 0% | 0/93 | 0% | 0/74 | 0% | 0/63 | 0% | | Increase > 2 D cylinder | 0/90 | 0% | 0/93 | 0% | 0/93 | 0% | 0/74 | 0% | 0/63 | 0% | | Preop BCVA-D ≤ 20/20 to >20/25 | 0/90 | 0% | 0/93 | 0% | 0/93 | 0% | 0/74 | 0% | 0/63 | 0% | | Loss of > 2 lines BCVA-N | 0/89 | 0% | 0/93 | 0% | 0/93 | 0% | 0/74 | 0% | 0/63 | 0% | | Loss of ≥ 2 lines BCVA-N | 0/89 | 0% | 0/93 | 0% | 0/93 | 0% | 0/74 | 0% | 0/63 | 0% | | BCVA-N worse than J3 | 0/89 | 0% | 0/93 | 0% | 0/93 | 0% | 0/74 | 0% | 0/63 | 0% | RCS-011-PRS Source: refractive pres nas skey tab.sas Date Generated: 27FEB04 Data Lock: 21JUL2003 31 P010018/S5 SSED 22 {22} Table 16a Summary of Key Safety Variables at Month 6, Stratified by Treatment Spots Applied Eyes Treated for Near with Intended Correction of 1.00 to 2.25 D | | 16 Spots | | 24 Spots | | | --- | --- | --- | --- | --- | | | 1.00 - 1.63 D | | 1.75 - 2.25 D | | | Safety Variables – Eyes Treated for Near | | | | | | Loss of > 2 lines BCVA-D | 0/42 | 0% | 0/50 | 0% | | Loss of ≥ 2 lines BCVA-D | 0/42 | 0% | 2/50 | 4% | | BCVA-D worse than 20/40 | 0/42 | 0% | 0/50 | 0% | | Increase > 2 D cylinder | 0/42 | 0% | 0/50 | 0% | | Preop BCVA-D ≤ 20/20 to >20/25 | 0/42 | 0% | 0/50 | 0% | | Loss of > 2 lines BCVA-N | 0/42 | 0% | 0/50 | 0% | | Loss of ≥ 2 lines BCVA-N | 0/42 | 0% | 0/50 | 0% | | BCVA-N worse than J3 | 0/42 | 0% | 0/50 | 0% | Note: Table excludes 1 eye treated intraoperatively with additional treatment spots for management of induced cylinder. RCS-011-PRS Source: refractec/pres sus keys_tab sus Date Generated: 18FEB04 Data Lock: 21JUL2003 Table 16b Summary of Key Safety Variables at Month 12, Stratified by Treatment Spots Applied Eyes Treated for Near with Intended Correction of 1.00 to 2.25 D | | 16 Spots | | 24 Spots | | | --- | --- | --- | --- | --- | | | 1.00 - 1.63 D | | 1.75 - 2.25 D | | | Safety Variables – Eyes Treated for Near | | | | | | Loss of > 2 lines BCVA-D | 0/34 | 0% | 0/29 | 0% | | Loss of ≥ 2 lines BCVA-D | 0/34 | 0% | 0/29 | 0% | | BCVA-D worse than 20/40 | 0/34 | 0% | 0/29 | 0% | | Increase > 2 D cylinder | 0/34 | 0% | 0/29 | 0% | | Preop BCVA-D ≤ 20/20 to >20/25 | 0/34 | 0% | 0/29 | 0% | | Loss of > 2 lines BCVA-N | 0/34 | 0% | 0/29 | 0% | | Loss of ≥ 2 lines BCVA-N | 0/34 | 0% | 0/29 | 0% | | BCVA-N worse than J3 | 0/34 | 0% | 0/29 | 0% | Note: Table excludes 1 eye treated intraoperatively for induced cylinder. RCS-011-PRS Source: refractec/pres sus keys_tab sus Date Generated: 07MAR04 Data Lock: 21JUL2003 P010018/S5 SSED 23 32 {23} Table 17 presents a summary of the adverse events reported in the clinical study of the ViewPoint™ CK System for the improvement of near vision. **Adverse Event Summary** | | Month 1* | | Month 3 | | Month 6 | | Month 9 | | Month 12 | | | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | | Late onset of haze beyond 6 months with loss of 2 lines (10 letters) or more BSCVA | 0/150 | 0% | 0/148 | 0% | 0/146 | 0% | 0/94 | 0% | 0/77 | 0% | | Decr. in BSCVA of > 10 letters not due to irreg. astig. as shown by hard contact lens refr., at 6 mo | 0/150 | 0% | 0/148 | 0% | 1/146 | 1% | 0/94 | 0% | 0/77 | 0% | | Any corneal epithelial defect involving the keratectomy site at 1 month or later | 0/150 | 0% | 0/148 | 0% | 0/146 | 0% | 0/94 | 0% | 0/77 | 0% | | Corneal infiltrate or ulcer | 0/150 | 0% | 0/148 | 0% | 0/146 | 0% | 0/94 | 0% | 0/77 | 0% | | Corneal edema at 1 month or later | 0/150 | 0% | 0/148 | 0% | 0/146 | 0% | 0/94 | 0% | 0/77 | 0% | | Corneal perforation | 0/150 | 0% | 0/148 | 0% | 0/146 | 0% | 0/94 | 0% | 0/77 | 0% | | Corneal microbial infection | 0/150 | 0% | 0/148 | 0% | 0/146 | 0% | 0/94 | 0% | 0/77 | 0% | | Corneal decompensation | 0/150 | 0% | 0/148 | 0% | 0/146 | 0% | 0/94 | 0% | 0/77 | 0% | | Corneal scar in visual axis | 0/150 | 0% | 0/148 | 0% | 0/146 | 0% | 0/94 | 0% | 0/77 | 0% | | Uncontrolled IOP with increase of > 5 mm Hg above baseline and any reading above 25 mm Hg | 0/150 | 0% | 0/148 | 0% | 0/146 | 0% | 0/94 | 0% | 0/77 | 0% | | IOP >25 mm Hg | 0/150 | 0% | 0/148 | 0% | 0/146 | 0% | 0/94 | 0% | 0/77 | 0% | | Intraocular infection | 0/150 | 0% | 0/148 | 0% | 0/146 | 0% | 0/94 | 0% | 0/77 | 0% | | Hypopyon | 0/150 | 0% | 0/148 | 0% | 0/146 | 0% | 0/94 | 0% | 0/77 | 0% | | Hyphema | 0/150 | 0% | 0/148 | 0% | 0/146 | 0% | 0/94 | 0% | 0/77 | 0% | | Onset of cataract unrelated to age, systemic disease, or trauma | 0/150 | 0% | 0/148 | 0% | 0/146 | 0% | 0/94 | 0% | 0/77 | 0% | | Retinal detachment | 0/150 | 0% | 0/148 | 0% | 0/146 | 0% | 0/94 | 0% | 0/77 | 0% | | Retinal vascular accidents | 0/150 | 0% | 0/148 | 0% | 0/146 | 0% | 0/94 | 0% | 0/77 | 0% | | Secondary surgical intervention other than CK treatment | 0/150 | 0% | 0/148 | 0% | 0/146 | 0% | 0/94 | 0% | 0/77 | 0% | | Death | 0/150 | 0% | 0/148 | 0% | 0/146 | 0% | 0/94 | 0% | 0/77 | 0% | | Other | 1/150 | 1% | 0/148 | 0% | 0/146 | 0% | 1/94 | 1% | 1/77 | 1% | | Not reported | 0/150 | 0% | 0/148 | 0% | 0/146 | 0% | 0/94 | 0% | 0/77 | 0% | Page 1 of 1 \* Includes adverse events reported from 1 day through 1 month postop. BCS-011-PRS Source: refractive press on air sub-sav Date Generated: 23/03/03 Date Lock: 21/03/2003 The following adverse event was reported as “Other” at one week at a rate of less than 1%: - Mild iritis During the first week following surgery, patients may experience: pain discomfort, a feeling of something in the eye (lasting from one up to three days after surgery), mild light sensitivity, and swelling of the cornea. P010018/S5 SSED 24 33 {24} Table 18 presents a summary of the complications reported in the clinical study. **Table 18** **Complication Summary** **Eyes Treated for Near** | | Month 1 | | Month 3 | | Month 6 | | Month 9 | | Month 12 | | | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | | Peripheral corneal epithelial defect at one month | 0/145 | 0% | 0/149 | 0% | 0/146 | 0% | 0/94 | 0% | 0/77 | 0% | | Corneal edema between one week and one month after | 0/145 | 0% | 0/149 | 0% | 0/146 | 0% | 0/94 | 0% | 0/77 | 0% | | Recurrent corneal erosion at one month or later | 0/145 | 0% | 0/149 | 0% | 0/146 | 0% | 0/94 | 0% | 0/77 | 0% | | Double/ghost images in the operative eye | 2/145 | 1% | 2/149 | 1% | 1/146 | 1% | 0/94 | 0% | 0/77 | 0% | | Foreign body sensation at one month or later | 1/145 | 1% | 0/149 | 0% | 1/146 | 1% | 1/94 | 1% | 1/77 | 1% | | Pain at one month or later | 0/145 | 0% | 0/149 | 0% | 0/146 | 0% | 0/94 | 0% | 0/77 | 0% | | Other | 2/145 | 1% | 2/149 | 1% | 0/146 | 0% | 0/94 | 0% | 0/77 | 0% | | Not reported | 0/145 | 0% | 0/149 | 0% | 0/146 | 0% | 0/94 | 0% | 0/77 | 0% | Page 1 of 1 RCS-011-PRS Source: refractive press.ias comp tab.ias Date Generated: 23JUL03 Data Lock: 21JUL2003 In the clinical study of the ViewPoint™ CK System for the improvement of near vision, the following complication was reported as “Other” on the day of surgery at a rate of <1%: - Treatment interruption (new tip needed after the 20th spot was applied due to bent tip) Each of the following complications were reported as “Other” at the one week visit at a rate of <1%: - Allergic conjunctivitis - Blepharitis The following complications were not reported in the clinical study, but could potentially occur following CK® procedure: peripheral corneal epithelial defect; corneal edema. 34 P010018/S5 SSED 25 {25} Table 19 below shows the absolute change in refractive cylinder for eyes treated for near. Table 19 Absolute Change in Refractive Cylinder Eyes Treated for Near with Intended Correction of 1.00 to 2.25 D | Astigmatism | Month 1 | | Month 3 | | Month 6 | | Month 9 | | Month 12 | | | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | | Increase >2.00 D | 0/90 | 0% | 0/93 | 0% | 0/93 | 0% | 0/74 | 0% | 0/63 | 0% | | Increase 2.00 D | 0/90 | 0% | 0/93 | 0% | 0/93 | 0% | 0/74 | 0% | 0/63 | 0% | | Increase 1.75 D | 0/90 | 0% | 0/93 | 0% | 0/93 | 0% | 0/74 | 0% | 0/63 | 0% | | Increase 1.50 D | 5/90 | 6% | 1/93 | 1% | 0/93 | 0% | 0/74 | 0% | 0/63 | 0% | | Increase 1.25 D | 6/90 | 7% | 8/93 | 9% | 6/93 | 6% | 2/74 | 3% | 1/63 | 2% | | Increase 1.00 D | 15/90 | 17% | 7/93 | 8% | 3/93 | 3% | 2/74 | 3% | 4/63 | 6% | | No Change (± 0.75 D) | 64/90 | 71% | 77/93 | 83% | 84/93 | 90% | 70/74 | 95% | 58/63 | 92% | | Decrease 1.00 D | 0/90 | 0% | 0/93 | 0% | 0/93 | 0% | 0/74 | 0% | 0/63 | 0% | | Decrease >1.00 D | 0/90 | 0% | 0/93 | 0% | 0/93 | 0% | 0/74 | 0% | 0/63 | 0% | | Not Reported | 0/90 | 0% | 0/93 | 0% | 0/93 | 0% | 0/74 | 0% | 0/63 | 0% | | Total | 90/90 | 100% | 93/93 | 100% | 93/93 | 100% | 74/74 | 100% | 63/63 | 100% | RCS-011-PBS Source: refractive pres.sas.crc1_sub.sas Date Generated: 18FEB04 Data Lock: 21JUL2003 35 P010018/S5 SSED 26 {26} Table 20 presents a comparison of eyes with ≥ 1.00 D induced cylinder and eyes with <1.00 D induced cylinder. Table 20 Comparison of Eyes with ≥ 1.00 D of Induced Cylinder and Eyes with < 1.00 D Induced Cylinder Eyes Treated for Near with Intended Correction of 1.00 to 2.25 D | | < 1.00 D Induced Cylinder | | | | | | ≥ 1.00 D Induced Cylinder | | | | | | | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | | | Month 6 | | Month 9 | | Month 12 | | Month 6 | | Month 9 | | Month 12 | | | Loss of > 2 lines BCVA-N | 0/84 | 0% | 0/70 | 0% | 0/58 | 0% | 0/9 | 0% | 0/4 | 0% | 0/5 | 0% | | Loss of 2 lines BCVA-N | 0/84 | 0% | 0/70 | 0% | 0/58 | 0% | 0/9 | 0% | 0/4 | 0% | 0/5 | 0% | | Loss of 1 line BCVA-N | 3/84 | 4% | 1/70 | 1% | 0/58 | 0% | 0/9 | 0% | 0/4 | 0% | 0/5 | 0% | | No Change | 67/84 | 80% | 59/70 | 84% | 49/58 | 84% | 5/9 | 56% | 3/4 | 75% | 5/5 | 100% | | Increase of 1 line BCVA-N | 13/84 | 15% | 9/70 | 13% | 9/58 | 16% | 3/9 | 33% | 1/4 | 25% | 0/5 | 0% | | Increase of 2 lines BCVA-N | 1/84 | 1% | 1/70 | 1% | 0/58 | 0% | 1/9 | 11% | 0/4 | 0% | 0/5 | 0% | | Increase of > 2 lines BCVA-N | 0/84 | 0% | 0/70 | 0% | 0/58 | 0% | 0/9 | 0% | 0/4 | 0% | 0/5 | 0% | | UCVA-N J1 or better | 42/84 | 50% | 33/70 | 47% | 20/58 | 34% | 4/9 | 44% | 1/4 | 25% | 2/5 | 40% | | UCVA-N J2 or better | 58/84 | 69% | 51/70 | 73% | 39/58 | 67% | 8/9 | 89% | 3/4 | 75% | 3/5 | 60% | | UCVA-N J3 or better | 66/84 | 79% | 57/70 | 81% | 45/58 | 78% | 9/9 | 100% | 4/4 | 100% | 4/5 | 80% | | UCVA-N J5 or better | 77/84 | 92% | 63/70 | 90% | 54/58 | 93% | 9/9 | 100% | 4/4 | 100% | 5/5 | 100% | | UCVA-N J7 or better | 81/84 | 96% | 67/70 | 96% | 56/58 | 97% | 9/9 | 100% | 4/4 | 100% | 5/5 | 100% | | UCVA-N | | | | | | | | | | | | | | N | 84 | | 70 | | 58 | | 9 | | 4 | | 5 | | | Mean | 2.44 | | 2.51 | | 2.74 | | 1.59 | | 1.92 | | 2.40 | | | 95% Confidence Interval | 1.95,2.93 | | 1.88,3.14 | | 2.07,3.41 | | 1.08,2.10 | | 0.98,2.86 | | 0.93,3.87 | | | Standard Deviation | 2.298 | | 2.719 | | 2.619 | | 0.794 | | 0.956 | | 1.673 | | | Median | 1.50 | | 2.00 | | 2.00 | | 2.00 | | 2.00 | | 2.00 | | | Range | 0.67,10.00 | | 0.67,16.00 | | 0.67,16.00 | | 0.67,3.00 | | 0.67,3.00 | | 1.00,5.00 | | BCS-011-PRS Source: refractive pres. sas. icbn_tab.sas Date Generated: 18FEB04 Data Lock: 21JUL2003 36 P010018/S5 SSED 27 {27} Table 21 below shows the absolute shift in cylinder axis. Table 21 Absolute Shift in Axis Eyes Treated for Near with Intended Correction of 1.00 to 2.25 D | Induced Shift | Month 6 | | | Month 9 | | | Month 12 | | | | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | | | n/N | % | 95% CI | n/N | % | 95% CI | n/N | % | 95% CI | | 0° | 20/93 | 22% | 0.137-0.312 | 17/74 | 23% | 0.140-0.342 | 16/63 | 0% | 0.153-0.379 | | 1° to 5° | 7/93 | 8% | 0.031-0.149 | 9/74 | 12% | 0.057-0.218 | 7/63 | 50% | 0.046-0.216 | | 6° to 10° | 8/93 | 9% | 0.038-0.162 | 5/74 | 7% | 0.022-0.151 | 7/63 | 0% | 0.046-0.216 | | 11° to 15° | 11/93 | 12% | 0.061-0.202 | 5/74 | 7% | 0.022-0.151 | 3/63 | 0% | 0.010-0.133 | | 16° to 20° | 2/93 | 2% | 0.003-0.076 | 3/74 | 4% | 0.008-0.114 | 4/63 | 0% | 0.018-0.155 | | 21° to 25° | 4/93 | 4% | 0.012-0.106 | 1/74 | 1% | 0.000-0.073 | 4/63 | 0% | 0.018-0.155 | | 26° to 30° | 1/93 | 1% | 0.000-0.058 | 2/74 | 3% | 0.003-0.094 | 1/63 | 50% | 0.000-0.085 | | 31° to 35° | 6/93 | 6% | 0.024-0.135 | 3/74 | 4% | 0.008-0.114 | 0/63 | 0% | 0.000-0.057 | | 36° to 40° | 3/93 | 3% | 0.007-0.091 | 5/74 | 7% | 0.022-0.151 | 2/63 | 0% | 0.004-0.110 | | 41° to 45° | 3/93 | 3% | 0.007-0.091 | 1/74 | 1% | 0.000-0.073 | 2/63 | 0% | 0.004-0.110 | | 46° to 50° | 2/93 | 2% | 0.003-0.076 | 4/74 | 5% | 0.015-0.133 | 3/63 | 0% | 0.010-0.133 | | 51° to 55° | 2/93 | 2% | 0.003-0.076 | 2/74 | 3% | 0.003-0.094 | 1/63 | 0% | 0.000-0.085 | | 56° to 60° | 5/93 | 5% | 0.018-0.121 | 2/74 | 3% | 0.003-0.094 | 2/63 | 0% | 0.004-0.110 | | 61° to 65° | 1/93 | 1% | 0.000-0.058 | 3/74 | 4% | 0.008-0.114 | 3/63 | 0% | 0.010-0.133 | | 66° to 70° | 1/93 | 1% | 0.000-0.058 | 2/74 | 3% | 0.003-0.094 | 1/63 | 0% | 0.000-0.085 | | 71° to 75° | 4/93 | 4% | 0.012-0.106 | 2/74 | 3% | 0.003-0.094 | 2/63 | 0% | 0.004-0.110 | | 76° to 80° | 6/93 | 6% | 0.024-0.135 | 3/74 | 4% | 0.008-0.114 | 1/63 | 0% | 0.000-0.085 | | 81° to 85° | 3/93 | 3% | 0.007-0.091 | 2/74 | 3% | 0.003-0.094 | 1/63 | 0% | 0.000-0.085 | | 86° to 90° | 4/93 | 4% | 0.012-0.106 | 3/74 | 4% | 0.008-0.114 | 3/63 | 0% | 0.010-0.133 | RCS-011-PRS Source: refractive pres. uas w2_tab.sus Date Generated: 18FEB04 Data Lnck 21/01/2003 37 P010018/S5 SSED 28 {28} Table 22 presents change in best spectacle corrected visual acuity at near for eyes treated for near. Table 22 Change in Best Spectacle Corrected Visual Acuity - Near Eyes Treated for Near with Intended Correction of 1.00 to 2.25 D | | Month 1 | | Month 3 | | Month 6 | | Month 9 | | Month 12 | | | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | | Decrease > 2 lines | 0/89 | 0% | 0/93 | 0% | 0/93 | 0% | 0/74 | 0% | 0/63 | 0% | | Decrease 2 lines | 0/89 | 0% | 0/93 | 0% | 0/93 | 0% | 0/74 | 0% | 0/63 | 0% | | Decrease 1 line | 11/89 | 12% | 7/93 | 8% | 3/93 | 3% | 1/74 | 1% | 0/63 | 0% | | No Change | 65/89 | 73% | 69/93 | 74% | 72/93 | 77% | 62/74 | 84% | 54/63 | 86% | | Increase 1 line | 11/89 | 12% | 15/93 | 16% | 16/93 | 17% | 10/74 | 14% | 9/63 | 14% | | Increase 2 lines | 2/89 | 2% | 2/93 | 2% | 2/93 | 2% | 1/74 | 1% | 0/63 | 0% | | Increase > 2 lines | 0/89 | 0% | 0/93 | 0% | 0/93 | 0% | 0/74 | 0% | 0/63 | 0% | | Not reported | 1/90 | 1% | 0/93 | 0% | 0/93 | 0% | 0/74 | 0% | 0/63 | 0% | | Total | 89/89 | 100% | 93/93 | 100% | 93/93 | 100% | 74/74 | 100% | 63/63 | 100% | RCS-011-PRS Source: refractec/pres/sas/cvm_tab.sas Date Generated: 18FEB04 Data Lock: 21JUL2003 Table 23 presents change in best spectacle corrected visual acuity at distance for eyes treated for near. Table 23 Change in Best Spectacle Corrected Visual Acuity - Distance Eyes Treated for Near with Intended Correction of 1.00 to 2.25 D | | Month 1 | | Month 3 | | Month 6 | | Month 9 | | Month 12 | | | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | | Decrease > 2 lines | 2/90 | 2% | 0/93 | 0% | 0/93 | 0% | 0/74 | 0% | 0/63 | 0% | | Decrease 2 lines | 1/90 | 1% | 1/93 | 1% | 2/93 | 2% | 0/74 | 0% | 0/63 | 0% | | Decrease 1 line | 33/90 | 37% | 14/93 | 15% | 12/93 | 13% | 6/74 | 8% | 5/63 | 8% | | No Change | 38/90 | 42% | 54/93 | 58% | 52/93 | 56% | 42/74 | 57% | 33/63 | 52% | | Increase 1 line | 16/90 | 18% | 23/93 | 25% | 24/93 | 26% | 24/74 | 32% | 23/63 | 37% | | Increase 2 lines | 0/90 | 0% | 1/93 | 1% | 2/93 | 2% | 2/74 | 3% | 2/63 | 3% | | Increase > 2 lines | 0/90 | 0% | 0/93 | 0% | 1/93 | 1% | 0/74 | 0% | 0/63 | 0% | | Not reported | 0/90 | 0% | 0/93 | 0% | 0/93 | 0% | 0/74 | 0% | 0/63 | 0% | | Total | 90/90 | 100% | 93/93 | 100% | 93/93 | 100% | 74/74 | 100% | 63/63 | 100% | RCS-011-PRS Source: refractec/pres/sas/cva_tab.sas Date Generated: 18FEB04 Data Lock: 21JUL2003 38 P010018/S5 SSED 29 {29} Subjects were asked to complete a questionnaire that allowed them to report any symptoms or complaints they had regarding their vision or ocular comfort following the CK* procedure. Changes in the patient symptoms reported from preoperative to 6, 9, and 12 months post-CK treatment are provided in Table 24. Table 24 Change in Patient Symptoms from Preoperative to 6, 9, and 12 Months Eyes Treated for Near with Intended Correction of 1.00 to 2.25 D | | Month 6 | | | | | | Month 9 | | | | | | Month 12 | | | | | | | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | | | Unchanged or Better | | Worse | | Significantly Worse | | Unchanged or Better | | Worse | | Significantly Worse | | Unchanged or Better | | Worse | | Significantly Worse | | | | n/N | % | n/N | % | n/N | % | n/N | % | n/N | % | n/N | % | n/N | % | n/N | % | n/N | % | | Light Sensitivity | 87/90 | 97 | 3/90 | 3 | 0/90 | 0 | 73/73 | 100 | 0/73 | 0 | 0/73 | 0 | 58/61 | 95 | 3/61 | 5 | 0/61 | 0 | | Headache | 89/90 | 99 | 1/90 | 1 | 0/90 | 0 | 70/72 | 97 | 2/72 | 3 | 0/72 | 0 | 60/60 | 100 | 0/60 | 0 | 0/60 | 0 | | Pain | 89/90 | 99 | 1/90 | 1 | 0/90 | 0 | 72/72 | 100 | 0/72 | 0 | 0/72 | 0 | 60/60 | 100 | 0/60 | 0 | 0/60 | 0 | | Redness | 90/91 | 99 | 1/91 | 1 | 0/91 | 0 | 73/73 | 100 | 0/73 | 0 | 0/73 | 0 | 61/61 | 100 | 0/61 | 0 | 0/61 | 0 | | Dryness | 88/92 | 96 | 4/92 | 4 | 0/92 | 0 | 69/74 | 93 | 4/74 | 5 | 1/74 | 1 | 61/62 | 98 | 1/62 | 2 | 0/62 | 0 | | Excessive Tearing | 91/91 | 100 | 0/91 | 0 | 0/91 | 0 | 73/73 | 100 | 0/73 | 0 | 0/73 | 0 | 61/61 | 100 | 0/61 | 0 | 0/61 | 0 | | Burning | 90/91 | 99 | 1/91 | 1 | 0/91 | 0 | 73/73 | 100 | 0/73 | 0 | 0/73 | 0 | 61/61 | 100 | 0/61 | 0 | 0/61 | 0 | | Gritty, Scratchy, or Sandy Feeling | 90/91 | 99 | 0/91 | 0 | 1/91 | 1 | 72/73 | 99 | 1/73 | 1 | 0/73 | 0 | 60/61 | 98 | 1/61 | 2 | 0/61 | 0 | | Glare | 85/91 | 93 | 5/91 | 5 | 1/91 | 1 | 67/73 | 92 | 5/73 | 7 | 1/73 | 1 | 57/61 | 93 | 2/61 | 3 | 2/61 | 3 | | Halos | 81/91 | 89 | 9/91 | 10 | 1/91 | 1 | 67/73 | 92 | 5/73 | 7 | 1/73 | 1 | 56/61 | 92 | 3/61 | 5 | 2/61 | 3 | | Blared Vision | 81/91 | 89 | 8/91 | 9 | 2/91 | 2 | 67/73 | 92 | 6/73 | 8 | 0/73 | 0 | 55/61 | 90 | 4/61 | 7 | 2/61 | 3 | | Double Vision | 86/91 | 95 | 4/91 | 4 | 1/91 | 1 | 68/73 | 93 | 5/73 | 7 | 0/73 | 0 | 54/61 | 89 | 6/61 | 10 | 1/61 | 2 | | Fluctuation of Vision | 82/91 | 90 | 8/91 | 9 | 1/91 | 1 | 70/73 | 96 | 3/73 | 4 | 0/73 | 0 | 56/61 | 92 | 4/61 | 7 | 1/61 | 2 | | Variation of Vision in Bright Light | 85/91 | 95 | 4/91 | 4 | 2/91 | 2 | 69/73 | 93 | 3/73 | 4 | 1/73 | 1 | 58/61 | 95 | 3/61 | 5 | 0/61 | 0 | | Variation of Vision in Normal Light | 88/90 | 98 | 1/90 | 1 | 1/90 | 1 | 71/72 | 99 | 1/72 | 1 | 0/72 | 0 | 56/60 | 93 | 3/60 | 5 | 1/60 | 2 | | Variation of Vision in Dirt Light | 86/90 | 96 | 2/90 | 2 | 2/90 | 2 | 69/72 | 96 | 3/72 | 4 | 0/72 | 0 | 54/60 | 90 | 3/60 | 5 | 3/60 | 5 | | Night Driving Vision Problems | 87/92 | 95 | 2/92 | 2 | 3/92 | 3 | 70/74 | 95 | 2/74 | 3 | 2/74 | 3 | 58/62 | 94 | 1/62 | 2 | 3/62 | 5 | | Other Symptom | 81/85 | 95 | 3/85 | 4 | 1/85 | 1 | 67/68 | 99 | 0/68 | 0 | 1/68 | 1 | 55/55 | 100 | 0/55 | 0 | 0/55 | 0 | Note: Unchanged or Better = 1 point increase, no change, or any decrease; Worse = 2 point increase, Significantly Worse = 3 point increase or greater. BCS-011-PRS Source: refractive-pres nas ps2_tab nas Date Generated: 10/18/04 Data Lock: 21JUL2003 39 P010018/S5 SSED 30 {30} Table 25 shows the incidence of "none," "mild," "moderate," "marked," and "very severe" for each symptom at baseline, 1 month, 6 months, and 12 months postoperative. While a clinically significant increase in postoperative symptoms was observed, the majority changed from "none" to "mild". The symptoms that reported a significant increase (>5%) from preoperative to 6 months or beyond in the "moderate" category are glare, halos, double vision, fluctuation of vision and variation of vision in dim light. Table 25 Patient Symptoms | Subjective Responses | None | Mild | Moderate | Marked | Very Severe | | --- | --- | --- | --- | --- | --- | | Light Sensitivity | | | | | | | Preop | 81% | 15% | 3% | 1% | 0% | | Month 1 | 56% | 31% | 10% | 2% | 1% | | Month 6 | 71% | 23% | 6% | 0% | 0% | | Month 12 | 76% | 19% | 5% | 0% | 0% | | Headaches | | | | | | | Preop | 92% | 5% | 0% | 1% | 1% | | Month 1 | 94% | 4% | 1% | 0% | 0% | | Month 6 | 94% | 5% | 1% | 0% | 0% | | Month 12 | 94% | 5% | 2% | 0% | 0% | | Pain | | | | | | | Preop | 98% | 2% | 0% | 0% | 0% | | Month 1 | 93% | 6% | 1% | 0% | 0% | | Month 6 | 97% | 2% | 1% | 0% | 0% | | Month 12 | 100% | 0% | 0% | 0% | 0% | | Redness | | | | | | | Preop | 94% | 6% | 0% | 0% | 0% | | Month 1 | 92% | 7% | 1% | 0% | 0% | | Month 6 | 96% | 3% | 1% | 0% | 0% | | Month 12 | 97% | 3% | 0% | 0% | 0% | | Dryness | | | | | | | Preop | 84% | 14% | 1% | 0% | 1% | | Month 1 | 67% | 24% | 7% | 1% | 1% | | Month 6 | 71% | 24% | 5% | 0% | 0% | | Month 12 | 79% | 19% | 2% | 0% | 0% | P010018/S5 SSED 31 40 {31} Table 25 Patient Symptoms (continued) | Subjective Responses | None | Mild | Moderate | Marked | Very Severe | | --- | --- | --- | --- | --- | --- | | **Excessive Tearing** | | | | | | | Preop | 96% | 2% | 2% | 0% | 0% | | Month 1 | 93% | 7% | 0% | 0% | 0% | | Month 6 | 96% | 3% | 0% | 1% | 0% | | Month 12 | 97% | 3% | 0% | 0% | 0% | | **Burning** | | | | | | | Preop | 97% | 1% | 2% | 0% | 0% | | Month 1 | 92% | 6% | 1% | 1% | 0% | | Month 6 | 92% | 6% | 1% | 0% | 0% | | Month 12 | 100% | 0% | 0% | 0% | 0% | | **Gritty, Scratchy or Sandy Feeling** | | | | | | | Preop | 92% | 6% | 1% | 0% | 0% | | Month 1 | 82% | 13% | 3% | 1% | 0% | | Month 6 | 88% | 11% | 0% | 1% | 0% | | Month 12 | 97% | 2% | 2% | 0% | 0% | | **Glare** | | | | | | | Preop | 94% | 5% | 1% | 0% | 0% | | Month 1 | 64% | 23% | 9% | 3% | 0% | | Month 6 | 65% | 27% | 8% | 1% | 0% | | Month 12 | 73% | 21% | 3% | 3% | 0% | | **Halos** | | | | | | | Preop | 96% | 3% | 1% | 0% | 0% | | Month 1 | 69% | 17% | 9% | 3% | 2% | | Month 6 | 72% | 15% | 12% | 1% | 0% | | Month 12 | 74% | 16% | 6% | 3% | 0% | | **Blurred Vision** | | | | | | | Preop | 81% | 12% | 6% | 0% | 1% | | Month 1 | 47% | 32% | 13% | 7% | 1% | | Month 6 | 59% | 27% | 11% | 3% | 0% | | Month 12 | 68% | 19% | 8% | 5% | 0% | | **Double Vision** | | | | | | | Preop | 97% | 3% | 0% | 0% | 0% | | Month 1 | 77% | 13% | 6% | 4% | 0% | | Month 6 | 83% | 12% | 4% | 0% | 1% | | Month 12 | 81% | 8% | 10% | 2% | 0% | P010018/S5 SSED 32 41 {32} Table 25 Patient Symptoms (continued) | Subjective Responses | None | Mild | Moderate | Marked | Very Severe | | --- | --- | --- | --- | --- | --- | | Fluctuation of Vision | | | | | | | Preop | 94% | 4% | 2% | 0% | 0% | | Month 1 | 51% | 33% | 12% | 3% | 0% | | Month 6 | 65% | 25% | 10% | 1% | 0% | | Month 12 | 69% | 23% | 6% | 2% | 0% | | Variation in Vision in Bright Light | | | | | | | Preop | 86% | 12% | 2% | 0% | 0% | | Month 1 | 63% | 24% | 9% | 3% | 0% | | Month 6 | 70% | 23% | 2% | 5% | 0% | | Month 12 | 84% | 11% | 3% | 2% | 0% | | Variation in Vision in Normal Light | | | | | | | Preop | 95% | 4% | 1% | 0% | 0% | | Month 1 | 70% | 20% | 9% | 1% | 0% | | Month 6 | 75% | 23% | 1% | 1% | 0% | | Month 12 | 81% | 13% | 5% | 2% | 0% | | Variation in Vision in Dim Light | | | | | | | Preop | 86% | 10% | 3% | 1% | 0% | | Month 1 | 61% | 27% | 9% | 3% | 0% | | Month 6 | 62% | 28% | 5% | 4% | 0% | | Month 12 | 65% | 21% | 10% | 3% | 2% | | Night Driving Vision Problems | | | | | | | Preop | 86% | 12% | 2% | 0% | 0% | | Month 1 | 61% | 22% | 10% | 6% | 1% | | Month 6 | 66% | 27% | 4% | 3% | 0% | | Month 12 | 82% | 10% | 3% | 3% | 2% | | Other Symptom | | | | | | | Preop | 100% | 0% | 0% | 0% | 0% | | Month 1 | 97% | 0% | 1% | 2% | 0% | | Month 6 | 95% | 1% | 3% | 1% | 0% | | Month 12 | 100% | 0% | 0% | 0% | 0% | 42 P010018/S5 SSED 33 {33} ## XI. CONCLUSIONS DRAWN FROM THE STUDIES The data in this application support reasonable assurance of the safety and efficacy of this device when used in accordance with the indications for use. ## XII. PANEL RECOMMENDATION On February 6, 2004, the Ophthalmic Device Advisory Panel recommended that the premarket approval application supplement for the ViewPoint™ CK System for the improvement of near vision be considered approvable with conditions. The conditions recommended by the panel were to: 1. Revise the first sentence of the indication for use statement as follows: - The Viewpoint CK System is indicated for the temporary induction of myopia (-1.00 D to -2.00 D) to improve near vision in the non-dominant eye of presbyopic hyperopes or presbyopic emmetropes, via spherical hyperopic treatment of 1.00 to 2.25 D. 2. Revise the patient and physician labeling. 3. Continue the clinical study out to 24 months and submit the data to FDA for review as a post market study. ## XIII. CDRH DECISION Following the panel meeting on February 6, 2004, FDA worked interactively with Refractec regarding the remaining issues. Generally, FDA agreed with the Panel's recommendations, and Refractec agreed to continue follow-up of subjects in their clinical study per the protocol out to the 24-month examination. Refractec submitted responses that adequately addressed all of FDA's concerns and labeling changes. CDRH issued and approval order on ____________________. ## XIV. APPROVAL SPECIFICATIONS - Postapproval Requirements and Restrictions: see Approval Order. - Hazards to Health from Use of the Device: see Indications, Contraindications, Warnings, Precautions, and Adverse Events in the labeling. - Directions for Use: see labeling. P010018/S5 SSED 34 43