U.S. Food and Drug Administration Clinical Trial of the Implantable Contact Lens for Moderate to High Myopia

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1 U.S. Food and Drug Administration Clinical Trial of the Implantable Contact Lens for Moderate to High The Implantable Contact Lens in Treatment of (ITM) Study Group * Purpose: To assess the safety and efficacy of the Implantable Contact Lens (ICL) to treat moderate to high myopia. Design: Prospective nonrandomized clinical trial. Participants: Five hundred twenty-three eyes of 291 patients with between 3 and 20.0 diopters (D) of myopia participating in the U. S. Food and Drug Administration clinical trial of the ICL for myopia. Intervention: Implantation of the ICL. Main Outcome Measures: Uncorrected visual acuity (UCVA), refraction, best spectacle-corrected visual acuity (BSCVA), adverse events, operative and postoperative complications, lens opacity analysis (Lens Opacity Classification System III), subjective satisfaction, and symptoms. Results: Twelve months postoperatively, 60.1% of patients had a visual acuity of 20/20 or better, and 92.5% had an uncorrected visual acuity of 20/40 or better. Patients averaged a line improvement in UCVA, 61.6% of patients were within 0.5 D, and 84.7% were within 1.0 D of predicted refraction. Only one case (0.2%) lost 2 lines of BSCVA. Gains of 2 or more lines of BSCVA occurred in 55 cases (11.8%) at 6 months and 41 cases (9.6%) at 1 year after ICL surgery. Early and largely asymptomatic, presumably surgically induced anterior subcapsular (AS) opacities were seen in 11 cases (2.1%); an additional early AS opacity (0.2%) was seen because of inadvertent anterior chamber irrigation of preservative-containing solution at surgery. Two (0.4%) late ( 1 year postoperatively) AS opacities were observed. Two (0.4%) ICL removals with cataract extraction and intraocular lens implantation have been performed. Patient satisfaction (very/extremely satisfied) was reported by 92.4% of subjects on the subjective questionnaire; only four patients (1.0%) reported dissatisfaction. Slightly more patients reported an improvement at 1 year over baseline values for the following subjective symptoms: quality of vision, glare, double vision, and night driving difficulties. Only a 3% difference between pre-icl and post-icl surgery was reported for haloes. Conclusions The results support the safety, efficacy, and predictability of ICL implantation to treat moderate to high myopia. Ophthalmology 2003;110: by the American Academy of Ophthalmology. Currently, the two most popular procedures for the correction of myopia are photorefractive keratectomy (PRK) and laser in situ keratomileusis (LASIK). Studies on PRK have shown it to effectively correct up to 6.00 diopters (D) of myopia. 1,2 However, studies have also shown that it is less effective and predictable on moderate or high myopia ( 6.00 D). 3,4 Complications from PRK on eyes with high myopia include corneal scarring, loss of best spectaclecorrected visual acuity (BSCVA), and regression. 5 In recent years, LASIK has emerged as the refractive corneal surgical procedure of choice for the correction of low myopia between 1.00 D and 6.00 D. Despite the widespread acceptance of LASIK within the ophthalmic Originally received: October 25, Accepted: August 2, Manuscript no Supported by STAAR Surgical, Monrovia, California. *The Appendix lists participants of the Study Group. Reprints requests to Darcy Smith, STAAR Surgical Company, 1911 Walker Avenue, Monrovia, CA community, this moderately invasive technique that directly affects the clear, central, optical zone is associated with a sizable number of potential intraoperative and postoperative complications; the incidence has been found to increase with higher refractive errors. In this moderate to high myopia population ( 6.00 D), an in- sufficient layer of untouched stromal base tissue can quickly lead to ectasia, which has been reported to significantly increase glare. 6,7 Additional complications include edema, pain, photophobia, flap/microkeratome complications including corneal penetration, 8 unstable refraction, loss of BSCVA, significant irregular astigmatism, corneal ectasia, 9 14 and diffuse lamellar keratitis, also known as Sands of Sahara Syndrome. 15 Furthermore, LASIK enhancements are commonplace, exposing the patient to these intraoperative risks on multiple occasions. Despite these complications, LASIK is performed widely and seems to be a good procedure for myopia of D. These current refractive surgical procedures for the correction of moderate to high myopia are generally based on 2003 by the American Academy of Ophthalmology ISSN /03/$ see front matter Published by Elsevier Science Inc. doi: /s (02)

2 Ophthalmology Volume 110, Number 2, February 2003 irreversible corneal alterations designed to permanently reshape the curvature of the cornea in such a way as to reduce the refractive error. Initial studies on phakic intraocular lenses (IOLs) have proven them to have good predictability with a low incidence of complications An initial report from the first phase of the U.S. Implantable Contact Lens (ICL) for Study, 19 in combination with international series, has found a high level of best-corrected vision preservation or improvement, minimal intraoperative/postoperative complications, a reduction in subjective patient symptoms, an early and stable improvement in vision, and a high degree of predictability in this refractive treatment for moderate to high myopia The U. S. FDA ICL Clinical Study for was initiated in May The primary objective of this article is to provide the initial report of 6-, 12-, and 24-month clinical outcomes (with the current V4 ICL lens design) through the third and final phase of the study. Patients and Methods Study Design The U.S. multicenter Food and Drug Administration (FDA) clinical study of the STAAR ICL (STAAR Surgical Co., Monrovia, CA) for myopia was designed as a prospective, nonrandomized clinical trial intended to evaluate the safety and efficacy of the ICL to treat moderate to high myopia. Twelve clinical sites across the United States enrolled 523 consecutive eyes of 291 patients between November 11, 1998 and July 25, 2001, that fulfilled the enrollment criteria described in the following. Standardized inclusion and exclusion criteria were used for study enrollment by all clinical investigators in accordance with the prospective Investigational Device Exemption clinical study protocol. Institutional review board approvals were obtained at each site before study initiation, and all study participants gave their informed consent. Patient Enrollment Criteria Patients were enrolled with baseline refractive errors between 3.00 to D of myopia (manifest refraction spherical equivalent [MRSE]). A maximum of 2.5 D of manifest refractive cylinder was allowed. Patients were required to have documented stable refraction for 12 months before study enrollment with a BSCVA of at least 20/100 in the study eye. All patients enrolled in the study were between 21 and 45 years old, and there were no restrictions as to gender or race. A patient s ability to comply with the standardized postoperative follow-up visits through the 2-year study period was taken into consideration during the enrollment process. Patients unable to tolerate contact lenses in the fellow eye were excluded from the study, as well as patients with an anterior chamber depth (ACD) of less than 2.8 mm (measured from the corneal endothelium to the anterior lens capsule) either by means of ultrasonography or with an Orbscan (Bausch & Lomb, Rochester, NY). Additional exclusion criteria included history and/or clinical signs of iritis/uveitis, diabetic retinopathy, glaucoma, previous ocular surgery (with the exception of astigmatic keratotomy), ocular hypertension, progressive sight-threatening disease other than myopia, monocular vision, pseudoexfoliation, and/or insulindependent diabetes. Study Outcomes/Patient Follow-up Patients were examined at 1 day, 1 week, 1 month, 3 months, 6 months, 12 months, and 24 months after ICL implantation. Monitoring systems were implemented at the onset of the study to ensure that a high level of follow-up was achieved through the prospective 2-year study end point. The main outcome measures were uncorrected visual acuity (UCVA), refraction, BSCVA, adverse events, operative and postoperative complications, lens opacity analysis (Lens Opacity Classification System III [LOCS III]), and subjective satisfaction and symptoms. Clarity of the crystalline lens was evaluated using LOCS III. 31 This standardized photographic grading system, generally used to assess the development of cataracts, classifies lens characteristics into four major categories: nuclear color, nuclear opalescence, cortical appearance, and posterior subcapsular appearance. Anterior subcapsular (AS) appearance used the same classification photographs as the posterior subcapsular region, but the slit lamp was used to further localize the opacity. A standardized subjective, self-administered questionnaire was used at all investigational sites at the preoperative and 12-month postoperative visits to obtain patients feedback regarding their satisfaction with the results of the ICL surgery, their quality of vision, and to report on changes in patient symptoms after ICL implantation compared with baseline. ICL for ICL Device. The subject of this study is a posterior chamber phakic IOL termed by its manufacturer the Implantable Contact Lens (STAAR Surgical Co., Monrovia, CA). The ICL is designed to vault anteriorly to the crystalline lens and is intended to have minimal contact with the natural lens. The lens is made from a new generation of biocompatible IOL materials termed Collamer. Collamer is composed of a proprietary, hydrophilic porcine collagen ( 0.1%)/hydroxyethyl methacrylate copolymer into which an ultraviolet-absorbing chromophore has been incorporated into the polymer chains. Its plate-haptic design resembles lenses already in use with cataract surgery; however, it incorporates distinct footplates and an anterior vault designed to minimize contact with the crystalline lens. This report addresses the current V4 ICL design. Lens Sizing and Power Calculation. Sizing of myopic lenses ( mm) was determined by the horizontal white-to-white measurement and the ACD measurement. For eyes with ACD measurements of 2.8 mm to 3.5 mm, the lens size was calculated by adding 0.5 mm to the horizontal white-to-white measurement. Eyes exhibiting an ACD greater than 3.5 mm required the addition of up to 1.0 mm to the white-to-white measurement, up to a maximum length of 13.0 mm. Patients with an ACD less than 2.8 mm were excluded from the study. Calculated lens sizes between the available lens diameters (in 0.5-mm steps) were generally rounded down if the ACD was 3.5 and rounded up if the ACD was 3.5 mm. White-to-white measurements were obtained using calipers at a slit lamp or using the Orbscan unit. All lens power calculations were performed by STAAR Surgical Co using a modified vertex formula. Surgical Procedure. Within 7 days of surgery, patients received two peripheral iridectomies performed 90 apart with a neodymium:yttrium aluminum garnet or argon krypton laser, generally at the 10:30 and 1:30 positions. The day of surgery, patients were administered dilating and cycloplegic agents, after which an anesthetic of the surgeon s choice was applied to the operative eye. A Model V4 ICL was inserted through a small, 3-mm, clear corneal incision. The lens was then injected through the incision into the anterior chamber (Staar MicroSTAAR injec- 256

3 Vukich et al The ICL for Table 1. Accountability Implantable Contact Lens Study Cohort Eyes 1 Day 1 Week 1 Month 3 Months 6 Months 12 Months 24 Months Available for analysis (number of eyes) % Accountability eyes available for analysis divided by ( enrolled minus discontinued minus not yet eligible for time interval ) 100% 96.2% 97.3% 92.9% 91.4% 90.1% 94.5% tor, STAAR Surgical Co., Monrovia, CA) and allowed to slowly unfold. Distal and then proximal footplates were tucked under the iris with a modified intraocular spatula. Correct positioning of the ICL in the center of the pupillary zone was verified before intraocular miotic was used to decrease pupil size. Any remaining viscoelastic was scrupulously irrigated out of the anterior chamber with balanced salt solution. Postoperative Management. Patients were administered 1 drop of Ocuflox (ofloxacin solution, 0.3%, Allergan Inc., Irvine, CA) and prescribed TobraDex (tobramycin and dexamethasone suspension; Alcon Laboratories, Ft. Worth, TX) four times daily for a total of 16 days, beginning with 1 drop four times daily for the first 4 postoperative days and steadily reducing the dosage by 1 drop every 4 days thereafter. Statistical Issues/Data Management Statistical analyses were performed using SPSS 10.0 (SPSS Inc., Chicago, IL). Data were compiled from the prospective, standardized case report forms and subjective patient questionnaires (in Access and Visual Basic databases) provided in the Investigational Device Exemption clinical study protocol. A sample size of 300 study subjects was selected because it provides a one-sided upper 95% confidence limit of 1% for unobserved complications/ adverse events computed using the binomial distribution. This 300-subject sample size is consistent with FDA and International Standards Organization recommendations for intraocular lens implant clinical investigations (FDA Draft IOL Guidance, October 14, 1999, and ISO/DIS , Annex B). Results Patient Population The ICL clinical study cohort is composed of 523 eyes from 291 subjects. This study cohort represents patients implanted with the current ICL design version, between November 1998 and July 2001, who fulfilled the enrollment criteria. Seventeen additional patients who did not fulfill the enrollment criteria (myopia 20 D, cylinder 2.5 D, age 45 years) were also implanted but are not reported as part of this cohort. Their exclusion did not significantly change the results or conclusions drawn from this study. One hundred seventy-six of the 291 subjects treated were female (60.5%). Most of the ICL PMA Cohort subjects (84.5%) were white. The mean age standard deviation at the time of the implantation of the STAAR ICL (primary eye surgery in bilateral subjects) was years, with a range of 22 to 45 years. Fifty-two (47 patients) of the 523 eyes (9.9%) in the myopia ICL clinical study were reported with preexisting ocular conditions. The most prevalent conditions included 18 eyes with myopic retinal degeneration, 20 eyes with amblyopia, and 9 eyes with early cataract; the latter were all visually insignificant. Twelve eyes had a history of prior ocular surgery in the study eye: astigmatic keratotomy (seven eyes), photocoagulation for retinal tears (three eyes), and muscle surgery (two eyes). The % Accountability was defined as Eyes Available for Analysis divided by ( number of eyes enrolled minus discontinued eyes minus eyes not yet eligible for time interval ), in accordance with FDA Guidance Document for Refractive Lasers ( Checklist for Information Usually Submitted in an Investigational Device Exemption (IDE) Application for Refractive Surgery Lasers September 5, 1997). In the ICL clinical study postoperative follow-up ranged between 90.1% and 100% for all postoperative visits through 24 months (Table 1). The decreasing numbers of patients available for analysis with time reflect the ongoing nature of the clinical trial. UCVA Preoperatively, in the cohort of cases with good visual potential (BSCVA 20/20 or better at baseline), no eyes (0%) were 20/80 or better, with only two eyes (0.6%) 20/200 or better uncorrected at Table 2. Uncorrected Visual Acuity Over Time in Patients with Preoperative Best Spectacle-Corrected Visual Acuity of 20/20 or Better Preoperative 1 Week 1 Month 3 Months 6 Months 12 Months 24 Months n % n % n % n % n % n % n % 20/20 or better 0/354 (0.0%) 150/340 (44.1%) 176/344 (51.2%) 195/332 (58.7%) 177/317 (55.8%) 176/293 (60.1%) 84/165 (50.9%) 20/25 or better 0/354 (0.0%) 214/340 (62.9%) 244/344 (70.9%) 253/332 (76.2%) 239/317 (75.4%) 219/293 (74.7%) 121/165 (73.3%) 20/32 or better 0/354 (0.0%) 266/340 (78.2%) 301/344 (87.5%) 292/332 (88.0%) 273/317 (86.1%) 249/293 (85.0%) 140/165 (84.8%) 20/40 or better 0/354 (0.0%) 303/340 (89.1%) 319/344 (92.7%) 314/332 (94.6%) 292/317 (92.1%) 271/293 (92.5%) 154/165 (93.3%) 20/80 or better 0/354 (0.0%) 332/340 (97.6%) 338/344 (98.3%) 328/332 (98.8%) 314/317 (99.1%) 286/293 (97.6%) 162/165 (98.2%) 20/200 or better 2/354 (0.6%) 340/340 (100.0%) 344/344 (100.0%) 332/332 (100.0%) 317/317 (100.0%) 293/293 (100.0%) 165/165 (100.0%) Worse than 352/354 (99.4%) 0/340 (0.0%) 0/344 (0.0%) 0/332 (0.0%) 0/317 (0.0%) 0/293 (0.0%) 0/165 (0.0%) 20/200 Not reported Total

4 Ophthalmology Volume 110, Number 2, February 2003 Figure 1. Uncorrected visual acuity over time in the cohort of cases with best spectacle-corrected visual acuity of 20/20 or better preoperatively. baseline (Table 2). At 6 months UCVA improved to 20/20 or better in 55.8% of patients and at one year it improved in 60.1% of patients after implantation of the ICL. The proportion of eyes with 20/40 or better UCVA at 6 and 12 months, respectively, was 92.1% and 92.5%. Furthermore, at the 2-year visit, 93.3% of eyes had improved to 20/40 or better. Of note, this improvement in UCVA to 20/40 or better with the myopia ICL occurred immediately in the first postoperative week and remained stable throughout the postoperative follow-up period (89.1%, 1 week; 92.7%, 1 month; 92.5%, 12 months; 93.3%, 24 months) (Fig 1). None of the cases reported had a loss in UCVA. Mean UCVA improvement was lines at 1 year postoperative. Refractive Outcomes MRSE. Preoperative MRSE for this study cohort ranged from 3.00 to D of myopia (mean, D). Only 21.2% of eyes had a preoperative myopia 7.0 D. At baseline, no eyes (0%) fell within 1.0 D (MRSE) compared with 86.1% at 12 months after ICL implantation (Table 3). Predictability of Manifest Refraction (Attempted versus Achieved). An ICL power calculation formula based on geometric optics was developed by the study sponsor. Myopic lenses were available from 3.0Dto 20.0 D. Some of the study eyes (9.9%) had more than 15 D of myopia preoperatively, which could not be fully corrected by the strongest available ICL power. These particular cases were targeted to be undercorrected. Table 4 presents the predictability of manifest refraction outcomes associated with implantation of the ICL for the correction of myopia for all eyes in the study cohort. Comparable to uncorrected visual acuity results, predictability was achieved immediately in the first postoperative week and maintained over the duration of the postoperative follow-up period, with 55.8% of eyes within 0.50 D and 80.6% within 1.0 D at the 1-week visit. At 6 months postoperatively, 60.3% of eyes were within 0.50 D of their attempted correction; 61.6% were within 0.50 D at 12 months. The percentage of eyes within 1.0 D at 6 months was 86.6% and 84.7% at the 12-month follow-up window. Fifteen cases (2.9%) underwent LASIK procedures at least 6 months after ICL implantation to treat residual refractive error. The post-lasik refractive data were not included in the predictability analysis. One patient had a 1-line decrease in BSCVA; otherwise, the remainder either were unchanged or improved after LASIK compared with the preoperative ICL BSCVA. Predictability Outcomes Stratified by Preoperative MR- SE. Table 5 contains predictability outcomes when study cohort eyes are stratified by their level of preoperative myopia into three MRSE groups: 7 D,7to10D,and 10 D. At the 12-month visit, 96.4% of eyes in the 7 D group fell within 1.0 D of their attempted correction, 91.9% in the 7 to 10 D group, and 73.8% in the 10 D group. Predictability outcomes for the three preoperative MRSE groups within 0.50 D were as follows: 75.0% ( 7 D group), 69.1% (7 10 D group), and 49.7% ( 10 D group). BSCVA BSCVA Over Time. BSCVA in the study cohort improved after ICL implantation compared with preoperative levels. At the 6-month and 12-month follow-up visits, 83.7% and 82.4% of eyes had a BSCVA of 20/20 or better compared with only 67.7% preoperatively. Furthermore, BSCVA 20/40 or better values improved to 98.7% (6 months) and 98.1% (12 and 24 months) from 96.9% before ICL surgery. No eyes had vision worse than 20/200 preoperatively or at any postoperative visit. Change in BSCVA. BSCVA was well preserved after ICL implantation, with only one eye (0.2%) losing more than 2 lines of Table 3. Manifest Refraction Spherical Equivalent with Time in Patients with an Implantable Contact Lens for Moderate to High Spherical Preoperative 1 Week 1 Month 3 Months 6 Months 12 Months 24 Months Equivalent n % n % n % n % n % n % n % 1.01 D 0 (0.0%) 3 (0.6%) 4 (0.8%) 5 (1.0%) 4 (0.9%) 1 (0.2%) 2 (0.8%) 1.00 to 0.01 D 0 (0.0%) 79 (16.0%) 101 (20.2%) 108 (22.5%) 94 (20.3%) 76 (17.9%) 32 (12.4%) 0.00 to 1.00 D 0 (0.0%) 336 (67.9%) 332 (66.3%) 313 (65.2%) 300 (64.7%) 289 (68.2%) 183 (70.9%) 1.01 to 2.00 D 0 (0.0%) 53 (10.7%) 39 (7.8%) 31 (6.5%) 43 (9.3%) 32 (7.5%) 23 (8.9%) 2.01 to 7.00 D 111 (21.2%) 22 (4.4%) 22 (4.4%) 20 (4.2%) 20 (4.3%) 24 (5.7%) 18 (7.0%) 7.01 to D 175 (33.5%) 2 (0.4%) 3 (0.6%) 3 (0.6%) 3 (0.6%) 2 (0.5%) 0 (0.0%) to D 185 (35.4%) 0 (0.0%) 0 (0.0%) 0 (0.0%) 0 (0.0%) 0 (0.0%) 0 (0.0%) to D 52 (9.9%) 0 (0.0%) 0 (0.0%) 0 (0.0%) 0 (0.0%) 0 (0.0%) 0 (0.0%) D 0 (0.0%) 0 (0.0%) 0 (0.0%) 0 (0.0%) 0 (0.0%) 0 (0.0%) 0 (0.0%) Total 523 (100.0%) 495 (100.0%) 501 (100.0%) 480 (100.0%) 464 (100.0%) 424 (100.0%) 258 (100.0%) Mean SD Range to to to to to to to 1.13 D diopters; SD standard deviation. 258

5 Table 4. Predictability of Manifest Refraction Attempted vs. Achieved in Patients with an Implantable Contact Lens for Moderate to High 1 Week Vukich et al The ICL for 1 Month 3 Months 6 Months 12 Months 24 Months 0.50 D 276/495 (55.8%) 301/501 (60.1%) 301/480 (62.7%) 280/464 (60.3%) 261/424 (61.6%) 148/258 (57.4%) 1.00 D 399/495 (80.6%) 420/501 (83.8%) 421/480 (87.7%) 402/464 (86.6%) 359/424 (84.7%) 207/258 (80.2%) 2.00 D 472/495 (95.4%) 480/501 (95.8%) 462/489 (96.3%) 443/464 (95.5%) 410/424 (96.7%) 247/258 (95.7%) Overcorrected 1 9/495 (1.8%) 10/501 (2.0%) 7/480 (1.5%) 7/464 (1.5%) 4/424 (0.9%) 6/258 (2.3%) Overcorrected 2 4/495 (0.8%) 1/501 (0.2%) 1/480 (0.2%) 0/464 (0.0%) 0/424 (0.0%) 0/258 (0.0%) Undercorrected 1 87/495 (17.6%) 71/501 (14.2%) 52/480 (10.8%) 55/464 (11.9%) 61/424 (14.4%) 45/258 (17.4%) Undercorrected 2 19/495 (3.8%) 20/501 (4.0%) 17/480 (3.5%) 21/464 (4.5%) 14/424 (3.3%) 11/258 (4.3%) Not reported Total D diopters. BSCVA between 1 and 24 months postoperatively (Table 6). This 42-year-old female with D myopia inadvertently received a carbachol solution containing preservative irrigated intracamerally at the end of ICL surgery instead of the intended preservativefree carbachol. She had transient corneal edema, which subsequently cleared, and vacuoles were noted in the AS region months postoperatively. At 6 months postoperatively, her BSCVA was 20/20 (compared with 20/20 preoperatively), but an AS cataract was present. Between 1 and 2 years postoperatively, her BSCVA decreased to 20/40 because of cataract. At 26 months postoperatively, an ICL removal cataract extraction with IOL implantation was performed with a final postoperative BSCVA of 20/20. Only six cases (1.1%) lost exactly 2 lines of BSCVA 6 months or later. One had a surgically induced opacity (lens touch at surgery because of removal and reinsertion of ICL) with a BSCVA of 20/25 (from 20/15); one had an early AS opacity decreasing vision from a preoperative BSCVA of 20/30 (because of amblyopia) to 20/50; one of these was due to a dry eye/irregular corneal surface; one case exhibited worsening myopic retinal degeneration; and the last two cases were transient findings, with BSCVA improving to within 1 line of preoperative values and both having a final BSCVA of 20/30 or better at the last visit. It should be noted that BSCVA improved 2 lines in 30 (7.0%) eyes and more than 2 lines in an additional 11 eyes (2.6%) at 12 months. The mean improvement in BSCVA ranged from 0.5 to 0.6 lines between 1 and 24 months postoperatively. Secondary Surgeries/Adverse Events Secondary surgical interventions were reported in 12 eyes (2.3%) in the study cohort. Four (0.7%) cases were repositioned; three within the first postoperative month and one at 11 months postoperatively. Two (0.4%) ICLs were replaced, because they were too long (at 2 and 3 days postoperatively); two (0.4%) ICLs were replaced because they were too short (at 3 weeks and 17 months postoperatively); one (0.2%) was replaced because of incorrect power (at 9 months postoperatively); one (0.2%) ICL was replaced for a longer lens (at 26 months postoperatively), but this second ICL was subsequently removed 4 months later, with no crystalline lens surgery required. In none of the preceding cases was there a loss of BSCVA. Two (0.4%) cases underwent ICL removal, cataract extraction, and IOL implantation. One 18 D myopic individual developed an AS opacity 12 months postoperatively. The second case was the patient described previously who experienced a surgical mishap when miotic with preservative was irrigated into the anterior chamber during surgery. No loss of BSCVA occurred after cataract extraction. Complications Surgical Complications. Eleven (2.1%) of the cases required ICL removal and reinsertion during surgery or the same day as surgery. These removals and subsequent reinsertions occurred as a result of the lens flipping (i.e., an ICL implanted upside down must be removed and reinserted). Six of these resulted in early AS lens opacities; one of these cases resulted in a 2-line loss of BSCVA. One additional case (0.2%) required repositioning during surgery. Except for the one case described previously, none of these cases had a loss of BSCVA. No other significant surgical complications occurred. Postoperative Complications. Complications after implantation of the ICL for the correction of myopia were extremely rare (Table 7). Only three (0.6%) complications were reported from 1 to 6 months after ICL implantation in the 523 study eyes; no complications were reported after 6 months through 24 months. No iritis or corneal edema at the incision site was observed after the first postoperative week. Postoperative complications included one retinal detachment at 6 months, one failed attempt to correct a slight ovalization of the pupil with argon laser synechiolysis at 6 months, and one treatment of an acute retinal hole at 3 months postoperative. There was one iris prolapse repair 1 day after surgery. None of the cases with postoperative complications lost BSCVA. Intraocular Pressure Twenty-one cases (4.0%) required secondary surgical intervention for management of acute pressure rises within a month after surgery because of small iridectomies (performed before ICL insertion) that were clogged with viscoelastic. Most of these secondary surgical interventions were additional yttrium aluminum garnet laser iridotomies to enlarge an existing iridotomy site (16 cases). Three cases involved irrigation of the anterior chamber, and there were two surgical iridectomies. All pressures returned to normal after the secondary procedures with no loss of BSCVA. Only one case (0.2%) was reported with intraocular pressure (IOP) more than 25 mmhg at 6 months or later. At 12 months postoperatively, the patient s IOP was 28 mmhg; however, it was less than 25 mmhg at five subsequent visits. At 24 months postoperatively the IOP was 22 mmhg with the patient on no pressurelowering medication. 259

6 Ophthalmology Volume 110, Number 2, February 2003 Table 5. Predictability of Manifest Refraction Attempted vs. Achieved Stratified by 7 diopters 6 Months 7 10 diopters 10 diopters 0.50 D 67/87 (77.0%) 120/162 (74.1%) 93/215 (43.3%) 1.00 D 85/87 (97.7%) 151/162 (93.2%) 166/215 (77.2%) 2.00 D 87/87 (100.0%) 161/162 (99.4%) 194/215 (90.2%) Overcorrected 1 0/87 (0.0%) 2/162 (1.2%) 5/215 (2.3%) Overcorrected 2 0/87 (0.0%) 0/162 (0.0%) 0/215 (0.0%) Undercorrected 1 2/87 (2.3%) 9/162 (5.6%) 44/215 (20.5%) Undercorrected 2 0/87 (0.0%) 1/162 (0.6%) 21/215 (9.8%) Not reported Total D diopters. It should be noted that no patients in the study cohort required long-term glaucoma medication, and there was no significant late elevation in IOP after implantation of the ICL for myopia. LOCS III Opacities Table 8 presents the distribution of LOCS III scores over time. Trace nuclear color remained relatively unchanged with 22.0% at baseline, 23.1% at 6 months, and 24.2% at 12 months postoperatively. The proportion of eyes with trace nuclear opalescence was also unchanged compared with baseline values (22.8% preoperative; 22.3% at 12 months). There was a reduction in the trace cortical score from 5.0% at baseline to 1.9% at the 12-month follow-up visit. Furthermore, all eyes had no or trace posterior subcapsular changes at all postoperative visits. AS opacities were seen with much greater frequency than in the other areas of the crystalline lens. Fourteen cases (2.7%) of AS lens opacities greater than trace have been reported in the ICL for myopia clinical study. Most of these lens opacities have been asymptomatic (patients are unaware of their presence) not affecting vision or requiring any treatment. AS lens opacities greater than trace ( 0.5 LOCS) can generally be divided into two groups; those occurring early ( 90 days postoperatively) and those occurring late ( 1 year postoperatively). Early (First Seen < 90 Days) AS Opacities. Early AS lens opacities occurred in 12 cases (1.9%); 75% were asymptomatic. These early cases seem to be due to surgically induced trauma and the surgeon s learning curve. One case caused by a miotic with preservative irrigated into the anterior chamber at the time of surgery progressed to ICL removal, cataract extraction, and subsequent IOL implantation because of glare and loss of BSCVA. Eight of these 12 cases (67%) were first observed during the first postoperative week. Late (> 1 Year) AS Opacities. Late AS opacities ( 1 year) were reported in two eyes (0.4%). In the first case, the vault seemed adequate, but a 1.5 AS opacity was noted 1 year after ICL surgery, which required ICL removal and cataract extraction/ IOL implantation. A second case (LOCS 1.0 ) resulting from surgical trauma during a lens replacement ultimately led to ICL removal but no crystalline lens extraction. There was no loss of BSCVA, and the patient was asymptomatic. Subjective Assessments Patients were asked to complete a self-administered standardized questionnaire both before ICL surgery and at the 12-month follow-up window. Of the 406 patients who answered the patient subjective evaluation questionnaire at 1 year, 92.4% (375 of 406) reported that they were very/extremely satisfied with the results of their surgery; only 1.0% (4 of 406) reported that they were unsatisfied. One unsatisfied patient had the preservative-containing irrigating solution at surgery, two were left mildly hyperopic, and one complained of difficulty wearing contacts for residual myopia. Patients were asked to report on the change in their subjective symptoms 12 months after surgery compared with before ICL Table 6. Change in Best Spectacle-corrected Visual Acuity in Patients with an Implantable Contact Lens for Moderate to High 1 Week 1 Month 3 Months 6 Months 12 Months 24 Months Decrease 2 lines 3/498 (0.6%) 0/501 (0.0%) 0/481 (0.0%) 0/464 (0.0%) 0/427 (0.0%) 1/257 (0.4%) Decrease 2 lines 6/498 (1.2%) 3/501 (0.6%) 1/481 (0.2%) 2/464 (0.4%) 3/427 (0.7%) 3/257 (1.2%) Decrease 1 line 56/498 (11.2%) 33/501 (6.6%) 18/481 (3.7%) 19/464 (4.1%) 23/427 (5.4%) 20/257 (7.8%) No change 252/498 (50.6%) 248/501 (49.5%) 221/481 (45.9%) 218/464 (47.0%) 189/427 (44.3%) 106/257 (41.2%) Increase 1 line 137/498 (27.5%) 163/501 (32.5%) 189/481 (39.3%) 170/464 (36.6%) 171/427 (40.0%) 99/257 (38.5%) Increase 2 lines 30/498 (6.0%) 37/501 (7.4%) 39/481 (8.1%) 41/464 (8.8%) 30/427 (7.0%) 19/257 (7.4%) Increase 2 lines 14/498 (2.8%) 17/501 (3.4%) 13/481 (2.7%) 14/464 (3.0%) 11/427 (2.6%) 9/257 (3.5%) Mean change Not reported Total

7 Dioptric Group in Patients with an Implantable Contact Lens for Moderate to High 7 diopters 12 Months 24 Months 7 10 diopters Vukich et al The ICL for 10 diopters 7 diopters 7 10 diopters 10 diopters 63/84 (75.0%) 103/149 (69.1%) 95/191 (49.7%) 32/40 (80.0%) 62/94 (66.0%) 54/124 (43.5%) 81/84 (96.4%) 137/149 (91.9%) 141/191 (73.8%) 38/40 (95.0%) 84/94 (89.4%) 85/124 (68.5%) 84/84 (100.0%) 148/149 (99.3%) 178/191 (93.2%) 40/40 (100.0%) 94/94 (100.0%) 113/124 (91.1%) 0/84 (0.0%) 3/149 (2.0%) 1/191 (0.5%) 0/40 (0.0%) 4/94 (4.3%) 2/124 (1.6%) 0/84 (0.0%) 0/149 (0.0%) 0/191 (0.0%) 0/40 (0.0%) 0/94 (0.0%) 0/124 (0.0%) 3/84 (3.6%) 9/149 (6.0%) 49/191 (25.7%) 2/40 (5.0%) 6/94 (6.4%) 37/124 (29.8%) 0/84 (0.0%) 1/149 (0.7%) 13/191 (6.8%) 0/40 (0.0%) 0/94 (0.0%) 11/124 (8.9%) implantation (Table 9). In terms of quality of vision, glare, double vision, and night driving difficulties, slightly more patients reported an improvement in these symptoms compared with their baseline scores. For haloes, there was a less than 3.0% difference between the percent of patients reporting an improvement versus a worsening in this symptom Discussion The 12-month clinical outcomes presented in this report from the ongoing U. S. FDA ICL Clinical Study for provide further assurance regarding the safety, effectiveness, and stability of the refractive ICL approach for the correction of moderate to high myopic refractive errors. In this section, current results from the U.S. FDA ICL Clinical Study for will be discussed supplemented by background data from earlier reports of international ICL series. Furthermore, to provide a more thorough analysis of the potential value of the ICL in our armamentarium of refractive surgical alternatives, ICL clinical study outcomes will be contrasted to the safety and effectiveness data available for FDA-approved myopic PRK and LASIK clinical studies. The excimer data presented have been reported in the published Safety and Effectiveness Summaries of the approved Premarket Approval Applications made available from the FDA through the Freedom of Information Act ,42 Table 10 summarizes the primary safety and efficacy variables for all excimer laser approvals for myopic or myopic astigmatism PRK where data have been stratified by the level of preoperative MRSE to allow for a review specifically of moderate to high myopia ( 6 or 7 D depending on the study). Table 11 summarizes the primary safety and efficacy variables for all excimer laser approvals for LASIK where data have been stratified by the level of preoperative MRSE to allow for a review specifically of moderate to high myopia ( 6or 7 D depending on the study). These higher myopia data were selected for comparison with the ICL study because in the latter only 21.2% of eyes had a preoperative myopia less than 7 D, whereas 9.9% had more than 15 D. Safety of the STAAR ICL From the perspective of safety, preliminary results from the 10-patient phase I U. S. FDA study demonstrated the potential of the ICL for providing a safe, reversible means of correcting moderate to high myopia. Sanders et al 19 reported an improvement in BSCVA after ICL implantation with no accompanying intraoperative or postoperative complications. Preservation of BSCVA, commonly considered the primary criterion for assessing the safety of a refractive surgical procedure, was extremely high in the larger study cohort presented in this article. Not only maintenance but also an improvement in best-corrected vision (20/20 or better) was achieved at 6 (83.7%) and 12 months (82.4%) compared with preoperative levels (67.7%). Only one eye Table 7. Postoperative Complications in Patients with an Implantable Contact Lens for Moderate to High 1 Day 1 Week 1 Month 3 Months 6 Months 12 Months 24 Months Iritis 101/523 (19.3%) 6/501 (1.2%) 0/505 (0.0%) 0/482 (0.0%) 0/468 (0.0%) 0/428 (0.0%) 0/258 (0.0%) Corneal edema 59/523 (11.3%) 2/501 (0.4%) 0/505 (0.0%) 0/482 (0.0%) 0/468 (0.0%) 0/428 (0.0%) 0/258 (0.0%) Retinal detachment 0/523 (0.0%) 0/501 (0.0%) 0/505 (0.0%) 0/482 (0.0%) 1/468 (0.2%) 0/428 (0.0%) 0/258 (0.0%) Iris prolapse repair 1/523 (0.2%) 0/501 (0.0%) 0/505 (0.0%) 0/482 (0.0%) 0/468 (0.0%) 0/428 (0.0%) 0/258 (0.0%) Treatment of acute retinal hole 0/523 (0.0%) 0/501 (0.0%) 0/505 (0.0%) 1/482 (0.2%) 0/468 (0.0%) 0/428 (0.0%) 0/258 (0.0%) Attempted argon laser synechiolysis 0/523 (0.0%) 0/501 (0.0%) 0/505 (0.0%) 0/482 (0.0%) 1/468 (0.2%) 0/428 (0.0%) 0/258 (0.0%) n/n 261

8 Ophthalmology Volume 110, Number 2, February 2003 Table 8. Distribution of Lens Opacity Classification System III Scores Over Time in Patients with an Implantable Contact Lens for Moderate to High Preoperative 1 Week 1 Month 3 Months 6 Months 12 Months 24 Months Nuclear color Clear (0) 407/523 (77.8%) 388/501 (77.4%) 388/504 (77.0%) 368/481(76.5%) 359/468 (76.7%) 322/426 (75.6%) 163/257 (63.4%) Trace (0.5) 115/523 (22.0%) 112/501 (22.4%) 115/504 (22.8%) 112/481(23.3%) 108/468 (23.1%) 103/425 (24.2%) 93/257 (36.2%) Mild (1) 0/523 (0.0%) 0/501 (0.0%) 0/504 (0.0%) 0/481 (0.0%) 0/468 (0.0%) 0/426 (0.0%) 0/257 (0.0%) Moderate (1.5 to 2) 1/523 (0.2%) 1/501 (0.2%) 1/504 (0.2%) 1/481 (0.2%) 1/468 (0.2%) 1/426 (0.2%) 1/257 (0.4%) Marked ( 2) 0/523 (0.0%) 0/501 (0.0%) 0/504 (0.0%) 0/481 (0.0%) 0/468 (0.0%) 0/426 (0.0%) 0/257 (0.0%) Nuclear Opalescence Clear (0) 400/523 (76.5%) 386/501 (77.0%) 386/504 (76.6%) 370/481(76.9%) 360/468 (76.9%) 329/426 (77.2%) 165/257 (64.2%) Trace (0.5) 119/523 (22.8%) 112/501 (22.4%) 115/504 (22.8%) 108/481(22.5%) 105/468 (22.4%) 95/426 (22.3%) 91/257 (35.4%) Mild (1) 3/523 (0.6%) 2/501 (0.4%) 2/504 (0.4%) 2/481 (0.4%) 2/468 (0.4%) 1/426 (0.2%) 0/257 (0.0%) Moderate (1.5 to 2) 1/523 (0.2%) 1/501 (0.2%) 1/504 (0.2%) 1/481 (0.2%) 1/468 (0.2%) 1/426 (0.2%) 1/257 (0.4%) Marked ( 2) 0/523 (0.0%) 0/501 (0.0%) 0/504 (0.0%) 0/481 (0.0%) 0/468 (0.0%) 0/426 (0.0%) 0/257 (0.0%) Cortical Clear (0) 495/523 (94.6%) 491/501 (98.0%) 495/504 (98.2%) 473/481(98.3%) 459/468 (98.1%) 417/426 (97.9%) 257/257 (100.0%) Trace (0.5) 26/523 (5.0%) 9/501 (1.8%) 8/504 (1.6%) 7/481 (1.5%) 7/468 (1.5%) 8/426 (1.9%) 0/257 (0.0%) Mild (1) 1/523 (0.2%) 1/501 (0.2%) 1/504 (0.2%) 0/481 (0.0%) 1/468 (0.2%) 1/426 (0.2%) 0/257 (0.0%) Moderate (1.5 to 2) 1/523 (0.2%) 0/501 (0.0%) 0/504 (0.0%) 1/481 (0.2%) 1/468 (0.2%) 0/426 (0.0%) 0/257 (0.0%) Marked ( 2) 0/523 (0.0%) 0/501 (0.0%) 0/504 (0.0%) 0/481 (0.0%) 0/468 (0.0%) 0/426 (0.0%) 0/257 (0.0%) Posterior subcapsular Clear (0) 519/523 (99.2%) 499/501 (99.6%) 502/504 (99.6%) 480/481(99.8%) 467/468 (99.8%) 426/426 (100.0%) 257/257 (100.0%) Trace (0.5) 4/523 (0.8%) 2/501 (0.4%) 2/504 (0.4%) 1/481 (0.2%) 1/468 (0.2%) 0/426 (0.0%) 0/257 (0.0%) Mild (1) 0/523 (0.0%) 0/501 (0.0%) 0/504 (0.0%) 0/481 (0.0%) 0/468 (0.0%) 0/426 (0.0%) 0/257 (0.0%) Moderate (1.5 to 2) 0/523 (0.0%) 0/501 (0.0%) 0/504 (0.0%) 0/481 (0.0%) 0/468 (0.0%) 0/426 (0.0%) 0/257 (0.0%) Marked ( 2) 0/523 (0.0%) 0/501 (0.0%) 0/504 (0.0%) 0/481 (0.0%) 0/468 (0.0%) 0/426 (0.0%) 0/257 (0.0%) Anterior Subcapsular Clear (0) 519/523 (99.2%) 475/501 (94.8%) 482/504 (95.6%) 459/481(95.4%) 447/468 (95.5%) 398/426 (93.4%) 238/257 (92.6%) Trace (0.5) 4/523 (0.8%) 21/501 (4.2%) 17/504 (3.4%) 18/481 (3.75%) 15/468 (3.2%) 22/426 (5.2%) 13/257 (5.1%) Mild (1) 0/523 (0.0%) 3/501 (0.6%) 2/504 (0.4%) 2/481 (0.4%) 4/468 (0.9%) 2/426 (0.5%) 4/257 (1.6%) Moderate (1.5 to 2) 0/523 (0.0%) 2/501 (0.4%) 3/504 (0.6%) 2/481 (0.4%) 2/468 (0.4%) 4/426 (0.5%) 2/257 (0.8%) Marked ( 2) 0/523 (0.0%) 0/501 (0.0%) 0/504 (0.0%) 0/481 (0.0%) 0/468 (0.0%) 0/426 (0.0%) 0/257 (0.0%) n/n (0.2%) lost more than 2 lines at any postoperative visit through 24 months, a result of a cataract caused by preservative-containing solution irrigated into the anterior chamber. After cataract extraction, vision returned to 20/20. Previously published ICL reports have also documented this unique improvement in best-corrected vision after implantation. BSCVA was maintained or improved in all eyes in these series (Gonvers et al, 21 Menezo et al, 22 and Pesando et al, 23 ), whereas only one eye with a loss was reported by Assetto et al 24 and Zaldivar et al. 25 In the U.S. ICL study, BSCVA improved 2 lines in 7% of eyes and more than 2 lines in an additional 2.6% of eyes at 12 months. Loss of BSCVA ( 2 lines) in the current ICL study (0.2% for all postoperative visits) was better than all excimer PRK studies (0.9%, 3.3%, 3.5%) and better or comparable to all LASIK studies (0%, 3.3%, 4.5%). Secondary surgeries, adverse events, and surgical complications, as anticipated, were rare in the U.S. ICL clinical study. The surgical technique closely resembles standard cataract extraction and IOL placement, and therefore the ICL surgical technique learning curve was expected and shown to be very short. Secondary surgeries involving the ICL were performed in only 12 eyes (2.3%) with no loss of best-corrected vision observed in these cases. These secondary ICL surgeries (2.3%) in combination with the 15 cases (2.9%) undergoing LASIK could be thought of as an enhancement rate when comparing the ICL with LASIK. Surgical complications Table 9. Change in Subjective Patient Symptoms (Preoperative to 12-month Postoperative in Patients with an Implantable Contact Lens for Moderate to High ) Quality of Vision Glare Haloes Double Vision Night Driving n % n % n % n % n % Improved 2 categories 23 (5.7%) 10 (2.5%) 12 (2.9%) 2 (0.5%) 17 (4.3%) Improved 1 category 105 (25.9%) 39 (9.6%) 29 (7.1%) 4 (1.0%) 37 (9.4%) No change 236 (58.3%) 325 (79.9%) 314 (77.1%) 397 (97.5%) 309 (78.4%) Worsened 1 category 39 (9.6%) 30 (7.4%) 38 (9.3%) 4 (1.0%) 23 (5.8%) Worsened 2 category 2 (0.5%) 3 (0.7%) 14 (3.4%) 0 (0.0%) 8 (2.0%) 262

9 Vukich et al The ICL for Table 10. Comparison of U. S. Implantable Contact Lens Study to U.S. Food and Drug Administration-approved Photorefractive Keratectomy Premarket Approval Applications Summary of Safety and Effectiveness Parameter U.S. Food and Drug Administration LaserSight Nidek Autonomous Procedure Implantable Contact Lens Photorefractive Keratectomy Photorefractive Keratectomy Photorefractive Keratectomy range (D) 3.0 to 20.0 D SE 6.0 to 10.0 D SE 7.0 to D SE 7.0 to 10.0 D sphere Mean preoperative NR NR NR myopia (D) Follow-up 12 mos 6 and 12 mos 6 mos 6 and 12 mos Number of cases 523 eyes 544 eyes 587 eyes 476 eyes* Predictability 0.50 D 61.6% (12 mos) 32.5% (6 mos) 42.8% (6 mos) 60.0% (6 mos) 35.0% (12 mos) 1.0 D 84.7% (12 mos) 52.6% (6 mos) 68.3% (6 mos) 76.7% (6 mos) 60.0% (12 mos) 2.0 D 96.7% (12 mos) 90.4% (6 mos) 86.2% (6 mos) NR 86.7% (12 mos) UCVA 20/40 or better 92.5% (12 mos) 67.0% (6 mos) 80.7% (6 mos) 86.2% (6 mos) 69.1% (12 mos) 20/20 or better 60.1% (12 mos) 32.1% (6 mos) 45.5% (6 mos) 48.3% (6 mos) 21.9% (12 mos) Loss of BSCVA 2 lines 0.2% (12 mos) 0.9% (6 mos) 3.5% (6 mos) NR 3.3% (12 mos) Best spectacle-corrected visual acuity 20/20 or better preoperative. *Sphere only eyes. BSCVA best spectacle-corrected visual acuity; D diopter; SE spherical equivalent; NR not reported; UCVA uncorrected visual acuity. were rare, largely involving flipping and reinserting the lens during the initial ICL implantation (2.1%). Furthermore, as previously reported in the literature, the safety of the ICL procedure is enhanced by the low incidence of postoperative and intraoperative complications. 19,25,28 The only complications observed after ICL implantation occurred within the first 6 months after surgery, with an absence of any long-term complications reported. Only three (0.6%) complications were reported from 1 to 6 months after ICL implantation in the 523 study eyes; no complications were reported after the 6-month visit through 24 months. Postoperative complications included one retinal detachment repair at 6 months, one failed attempt to correct a slight ovalization of the pupil with argon laser synechiolysis at 6 months, and one treatment of an acute retinal hole at 3 months postoperatively. There was one iris prolapse repair 1 day after surgery. Acute pressure rises that occurred in the early postoperative period were managed effectively by postoperative yttrium aluminum garnet laser iridotomies, surgical iridectomies, or anterior chamber irrigation in 4.1% of cases. All pressures returned to normal after these procedures. Of note, no patients in the study cohort required long-term glaucoma medication, and there was no significant late elevation in IOP (0.4%) after implantation of the ICL for myopia. Reports of lens opacities/cataract development after implantation of earlier versions of the ICL have been published from international series. 31,41 Data from these European series in most cases involved the use of the V3 and C3 ICL designs, which had substantially less vault, rather than the V4 ICL lens design discussed in this report. On the basis of these earlier reports, to adequately evaluate the incidence of lens opacities in this study, the standardized LOCS III grading system for lens opacities was used across all centers. With the exception of AS changes, the distribution of all other parameters remained unchanged (trace nuclear color, trace nuclear opalescence, cortical or posterior subcapsular). A small number of lens opacities were reported with this newer version of the ICL. Most importantly, of the 12 early AS lens opacities that were identified, most (8 of 12 or 67%) occurred in the first week after surgery, and most cases were asymptomatic (75%). These early AS opacities seem to be due to surgically induced trauma and the surgeon s learning curve and are detected almost immediately after surgery during the initial healing phase. The key question therefore has been whether a progressive/late lens opacification is associated with the ICL procedure. Late AS opacities ( 1 year) were reported in only two cases, (0.4%), and only one of these was likely due to improper sizing of the ICL length. Longer term follow-up may be necessary to fully evaluate the real risk of clinically significant late AS opacities. The incidence of subjective patient symptoms showed a slight improvement (glare, double vision, quality of vision, night driving difficulties) compared with before surgery in contrast to other refractive surgery procedures in which large increases in symptoms are commonly reported. In summary, the outcomes of this study clearly support the overall short-term and intermediate-term safety of ICL surgery. Both intraoperative and postoperative complications were low, no late complications were reported, and ICL surgery did not preclude a successful subsequent cataract extraction and IOL implantation in this patient popula- 263

10 Ophthalmology Volume 110, Number 2, February 2003 Table 11. Comparison of U.S. Implantable Contact Lens Study to U.S. Food and Drug Administration Approved LASIK Parameter U.S. Food and Drug Administration Nidek Autonomous Procedure Implantable Contact Lens Laser In Situ Keratomileusis Laser In Situ Keratomileusis range (D) 3.0 to 20.0 D SE 7.0 to 20.0 D sphere 4.0 D cyl 7.0 to 11.0 D sphere 0.50 to 6.0 D cyl Mean preoperative myopia (D) D 3.75 D NR NR Follow-up 12 mos 6 and 12 mos 3 mos Number of cases 523 eyes 1126 eyes 177 eyes* Predictability 0.50 D 61.6% (12 mos) 64.5% (12 mos) NR 1.0 D 84.7% (12 mos) 73.3% (6 mos) 86.4% (3 mos) 77.2% (12 mos) 2.0 D 96.7% (12 mos) 92.7% (6 mos) 100% (3 mos) 94.4% (12 mos) UCVA 20/40 or better 92.5% (12 mos) NR 85.7% (3 mos) 20/20 or better 60.1% (12 mos) NR 71.4% (3 mos) Loss of BSCVA 2 lines 0.2% (12 mos) NR 4.5% (3 mos) *Sphere only eyes. Best spectacle-corrected visual acuity 20/20 or better preoperative. BSCVA best spectacle-corrected visual acuity; D diopters; NR not reported; SE spherical equivalent; UCVA uncorrected visual acuity. tion. The incidence of best-corrected vision loss ( 2 lines) is substantially lower than PRK rates and lower than or comparable to approved U.S. LASIK studies, despite the large proportion of high myopes in the ICL clinical study. Preservation and even improvement of best-corrected vision is a key benefit of this technique. Effectiveness of the STAAR ICL Preliminary data from the phase I U.S. FDA ICL clinical study reported 80% of eyes within 0.25 D of emmetropia in conjunction with 100% of eyes 20/30 or better UCVA. 19 The U.S. ICL clinical study involved the enrollment of patients with myopia (MRSE) up to D and a highest lens power of D, resulting in intended undercorrection in the higher myopes. UCVA, the primary efficacy variable for the ICL clinical study and most refractive surgeries, showed great improvement over preoperative values. A mean line improvement between the 1-year and preoperative visits was lines. Uncorrected acuity improved in the immediate first postoperative week and remained stable throughout the follow-up period, supporting the value of the implantable lens concept. Uncorrected vision jumped from 0% of patients with 20/80 or better to 89.1% with 20/40 or better at 1 week; with a slight continued improvement over the follow-up period (92.1% [6 months], 92.5% [12 months], and 93.3% [24 months]). The proportion of eyes with 20/20 or better also showed a substantial improvement, rising from 0% preoperatively to 60.1% at 1 year. These results with the ICL are better or comparable to those reported in the approved excimer studies. For PRK, the proportion of eyes 20/20 or better ranged from 21.9% to 48.3% compared with a higher rate of 60.1% with the ICL. The ICL outcome (92.5%) was also better at 20/40 or better compared with PRK percentages of 69.1% to 86.2%. The ICL was better or comparable to LASIK outcomes with the incidence of 20/20 or better ranging from 14.6% to 71.4% (ICL: 60.1%) and 20/40 or better ranging from 67.1% to 93.6% (ICL: 92.5%). The ICL percentage was better than all but one LASIK study for both 20/20 and 20/40 or better UCVA. Again, the degree of preoperative myopia was substantially higher in the ICL cases than in the LASIK cases. Predictability with the ICL is excellent and compares favorably with both PRK and LASIK outcomes. ICL results at all three predictability breakdowns ( 0.50 D, 1.0 D, and 2.0 D) were better than all reported PRK studies. The proportion of eyes with 0.50 D in the ICL study was 61.6% compared with that of PRK (32.5%, 35.0%, 42.8%, and 60.0%). For eyes within 1.0 D, again the ICL had a higher percentage of cases (84.7%) compared with that of PRK, ranging between 52.6% and 76.7%. Within 2.0 D of the attempted correction, PRK studies were between 86.2% and 90.4%, lower than the 96.7% reported in the ICL study. Comparing the ICL and LASIK predictability outcomes, the proportion of eyes falling within 0.50 D, 1.0 D, and 2.0 D were better than the reported LASIK figures in most studies and comparable to all LASIK studies. For 0.50 D of the attempted correction, 61.6% of ICL cases fell in this range compared with LASIK (42.3%, 44.2%, 47.2%, 60.6%, 64.5%). In the ICL study, 84.7% fell within 1.0 D compared with between 62.5% and 86.4% in the LASIK studies; the ICL better than all but one study). And for the proportion of eyes falling within 2.0 D, the ICL outcome of 96.7% was better than all but one LASIK study (83.9% to 100%). Subjective patient satisfaction was high 1 year after ICL surgery, reflecting the positive acceptance of this procedure by the moderate and high myopic patient population, who currently have fewer optimal alternatives for the correction 264

11 Keratomileusis Premarket Approval Applications Summary of Safety and Effectiveness Summit Kremer Visx Dishler Laser In Situ Laser In Situ Keratomileusis Keratomileusis Laser In Situ Keratomileusis 7.0 to 14 D sph 0.5 Vukich et al The ICL for Laser In Situ Keratomileusis to 5.0 D cyl 7.0 to 15.0 D sphere 5.0 D cyl 7.0 to 14.0 D SE 0.25 to 6.0 D cyl NR NR NR NR 6 mos 6 and 12 mos 6 mos 6 and 12 mos 428 eyes* 1140 eyes 1276 eyes 839 eyes 7.0 to 24 D sph 7 D cyl 44.2% (6 mos) 42.3% (6 mos) 60.6% (6 mos) 47.2% (6 mos) 76.1% (6 mos) 62.5% (6 mos) 82.2% (6 mos) 72.2% (6 mos) 92.0% (6 mos) 83.9% (6 mos) 96.9% (6 mos) 91.7% (6 mos) 93.6% (6 mos) 67.1% (6 mos) 91.7% (6 mos) 72.2% (6 mos) 35.2% (6 mos) 14.6% (6 mos) 43.6% (6 mos) 30.6% (6 mos) 3.3% (6 mos) NR 0% (6 mos) NR of their high refractive errors. At 1 year, 92.4% reported that they were very/extremely satisfied with the results of their surgery; only 1.0% stated that they were unsatisfied. In summary, this study leads to the conclusion that the current ICL design offers a safe, effective, and stable alternative for the correction of moderate to high myopia. These clinical outcomes are better or comparable to existing refractive surgery alternatives. The Implantable Contact Lens for (ITM) Study Group The participants in the ITM Study Group as of October 2001 are as follows: John A. Vukich, MD,* Davis Duehr Dean Medical Center, Madison, Wisconsin Donald R. Sanders, MD, PhD,* Kimberley Doney, MBA, Center for Clinical Research, Chicago, Illinois Ronald Barnett, MD, David Dulaney, MD, Scott Perkins, MD, The Barnett Dulaney Eye Center, Phoenix, Arizona Sheri L. Rowen, MD, Rowen Laser Vision & Correction Center, Towson, Maryland Douglas Steel, MD, Advance Sight Medical Group, Los Angeles, California Ralph Berkeley, MD, Michael Caplan, MD, Paul Mann, MD, Houston Microsurgery Center, Houston, Texas Stephen Bylsma, MD, Shepard Eye Center, Santa Maria, California R. Gale Martin, MD, Carolina Eye Associates, Southern Pines, North Carolina David C. Brown, MD, Eye Centers of Florida, Fort Myers, Florida Harry Grabow, MD, Sarasota Cataract Institute, Sarasota, Florida Charles H. Williamson, MD, Williamson Eye Center, Baton Rouge, Louisiana John R. Shepherd, MD, Shepherd Eye Center, Las Vegas, Nevada Howard Fine, MD, Oregon Eye Surgery Center, Eugene, Oregon Manus Kraff, MD, Kraff Eye Institute, Chicago, Illinois Robert Fabricant, MD, Pacific Eye Institute, Upland, California Alan Berg, MD, Advanced Vision Correction Centers, Burbank, California Monica Gaston, Nancy Hall, Darcy Smith, STAAR Surgical, Monrovia, California *Dr. Vukich, Dr. Bylsma, Dr. Brown, and Dr. Sanders are paid consultants to STAAR Surgical Dr. Sanders, Dr. Vukich, Ms. Doney, and Ms. Gaston participated in the writing of this manuscript. References 1. Kim JH, Hahn TW, Lee YC, Sah WJ. Excimer laser photorefractive keratectomy for myopia: two year follow-up. J Cataract Refract Surg 1994;20(Suppl):S Maguen E, Salz JJ, Nesburn AB, et al. Results of excimer laser photorefractive keratectomy for the correction of myopia. Ophthalmology 1994;101: discussion Pietilä J, Mäkinen P, Pajari S, et al. Photorefractive keratectomy for 1.25 to diopters of myopia. J Refract Surg 1998;14: Heitzmann J, Binder PS, Kassar BS, Nordan LT. The correction of high myopia using the excimer laser. Arch Ophthalmol 1993;111: Seiler T, Holschbach A, Derse M, et al. Complications of myopic photorefractive keratectomy with the excimer laser. Ophthalmology 1994;101: Hersh PS, Steinert RF, Brint SF. Photorefractive keratectomy 265

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