Sanders DR, Vukich JA, Doney K, Gaston M; Implantable Contact Lens in Treatment of Myopia Study Group. U.S.

Food and Drug Administration clinical trial of the Implantable Contact Lens for moderate to high myopia. Ophthalmology. 2003 Feb;110(2):255-66.
Lens sizing and power calculation
Sizing of myopic lenses (11.513.0 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.

U.S. Food and Drug Administration clinical trial of the Implantable Contact Lens for moderate to high myopia The Implantable Contact Lens in Treatment of Myopia (ITM) Study Group *, <img alt="Corresponding author contact information" src="http://origin-cdn.els-cdn.com/sd/entities/REcor.gif"> Received 25 October 2001 Accepted 2 August 2002 Available online 5 February 2003 http://dx.doi.org/10.1016/S0161-6420(02)01771-2, How to Cite or Link Using DOI Permissions & Reprints Abstract 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 10.31-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. 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 and 2 However, studies have also shown that it is less effective and predictable on moderate or high myopia (6.00 D).3 and 4 Complications from PRK on eyes with high myopia include corneal scarring, loss of best spectacle-corrected 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 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 and 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, 10, 11, 12, 13 and 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 <10.00 D. These current refractive surgical procedures for the correction of moderate to high myopia are generally based on 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.16, 17 and 18 An initial report from the first phase of the U.S. Implantable Contact Lens (ICL) for Myopia Study,19 in combination with international series, has found a high level of bestcorrected 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.20, 21, 22, 23, 24, 25, 26, 27, 28, 29 and 30 The U. S. FDA ICL Clinical Study for Myopia was initiated in May 1997. 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 20.00 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 patients 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 myopia 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 (11.513.0 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:yttriumaluminumgarnet or argonkrypton 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 surgeons 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 injector, 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 119797, Annex B). Results Patient population The Myopia 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 Myopia ICL PMA Cohort subjects (84.5%) were white. The mean age standard deviation at the time of the implantation of the STAAR Myopia ICL (primary eye surgery in bilateral subjects) was 36.5 5.9 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 Myopia 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. Table 1. AccountabilityImplantable Contact Lens Study Cohort Eyes 1 1 1 3 6 12 24 Day Week Month Months Months Months Months Available for analysis (number of eyes) 523 501 505 482 468 428 258 % Accountability = eyes available for analysis divided by (enrolled minus 100% 96.2% 97.3% 92.9% 91.4% 90.1% 94.5% discontinued minus not yet eligible for time interval) Full-size table Table options View in workspace Download as CSV 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 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.

Table 2. Uncorrected Visual Acuity Over Time in Patients with Preoperative Best Spectacle-Corrected Visual Acuity of 20/20 or Better Preoperativ 1 Week 1 Month 3 Months 6 Months 12 Months 24 Months e n % n % n % n % n % n % n % 20/20 (0.0% 150/3 (44.1 176/3 (51.2 195/3 (58.7 177/3 (55.8 176/2 (60.1 84/16 (50.9 or 0/354 ) 40 %) 44 %) 32 %) 17 %) 93 %) 5 %) better 20/25 (0.0% 214/3 (62.9 244/3 (70.9 253/3 (76.2 239/3 (75.4 219/2 (74.7 121/1 (73.3 or 0/354 ) 40 %) 44 %) 32 %) 17 %) 93 %) 65 %) better 20/32 (0.0% 266/3 (78.2 301/3 (87.5 292/3 (88.0 273/3 (86.1 249/2 (85.0 140/1 (84.8 or 0/354 ) 40 %) 44 %) 32 %) 17 %) 93 %) 65 %) better 20/40 (0.0% 303/3 (89.1 319/3 (92.7 314/3 (94.6 292/3 (92.1 271/2 (92.5 154/1 (93.3 or 0/354 ) 40 %) 44 %) 32 %) 17 %) 93 %) 65 %) better 20/80 (0.0% 332/3 (97.6 338/3 (98.3 328/3 (98.8 314/3 (99.1 286/2 (97.6 162/1 (98.2 or 0/354 ) 40 %) 44 %) 32 %) 17 %) 93 %) 65 %) better 20/20 (0.6% 340/3 (100.0 344/3 (100.0 332/3 (100.0 317/3 (100.0 293/2 (100.0 165/1 (100.0 0 or 2/354 ) 40 %) 44 %) 32 %) 17 %) 93 %) 65 %) better Worse than 352/3 (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%) 20/20 54 %) 0 Not report 0 0 0 0 1 0 0 ed Total 354 340 344 332 318 293 165 Full-size table Table options View in workspace Download as CSV 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 10.31 lines at 1 year postoperative.

<img class="figure large" border="0" alt="Fullsize image (10 K)" src="http://origin-ars.els-cdn.com/content/image/1-s2.0-S0161642002017712-gr1.gif" datathumbEID="1-s2.0-S0161642002017712-gr1.sml" data-fullEID="1-s2.0-S0161642002017712-gr1.gif"> Figure 1. Uncorrected visual acuity over time in the cohort of cases with best spectacle-corrected visual acuity of 20/20 or better preoperatively. Figure options View in workspace Download full-size image Download as PowerPoint slide Refractive outcomes MRSE Preoperative MRSE for this study cohort ranged from 3.00 to 20.00 D of myopia (mean, 10.046 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). Table 3. Manifest Refraction Spherical Equivalent with Time in Patients with an Implantable Contact Lens for Moderate to High Myopia 1 Month 3 Months 6 Months 12 Months 24 Months Spherical Preoperative 1 Week Equivalen t 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 (0.0%) 79 (16.0%) 101 (20.2%) 108 (22.5%) 94 (20.3%) 76 (17.9%) 32 (12.4%) +0.01 D 0.00 to 0 (0.0%) 336 (67.9%) 332 (66.3%) 313 (65.2%) 300 (64.7%) 289 (68.2%) 183 (70.9%) 1.00 D 1.01 to 0 (0.0%) 53 (10.7%) 39 (7.8%) 31 (6.5%) 43 (9.3%) 32 (7.5%) 23 (8.9%) 2.00 D 2.01 to 111 (21.2%) 22 (4.4%) 22 (4.4%) 20 (4.2%) 20 (4.3%) 24 (5.7%) 18 (7.0%) 7.00 D 7.01 to 175 (33.5%) 2 (0.4%) 3 (0.6%) 3 (0.6%) 3 (0.6%) 2 (0.5%) 0 (0.0%) 10.00 D 10.01 to 185 (35.4%) 0 (0.0%) 0 (0.0%) 0 (0.0%) 0 (0.0%) 0 (0.0%) 0 (0.0%) 15.00 D 15.01 to 52 (9.9%) 0 (0.0%) 0 (0.0%) 0 (0.0%) 0 (0.0%) 0 (0.0%) 0 (0.0%) 20.00 D >20.00 D 0 (0.0%) 0 (0.0%) 0 (0.0%) 0 (0.0%) 0 (0.0%) 0 (0.0%) 0 (0.0%)

1 Month 3 Months 6 Months 12 Months 24 Months Spherical Preoperative 1 Week Equivalen t n % n % n % n % n % n % n % (100.0% (100.0% (100.0% (100.0% (100.0% (100.0% (100.0% Total 523 495 501 480 464 424 258 ) ) ) ) ) ) ) Mean 10.046 0.526 0.448 0.380 0.436 0.496 0.564 SD 3.748 0.950 0.994 1.019 1.061 0.984 0.980 20.00 to 7.88 to 8.13 to 8.25 to 9.63 to 8.00 to 5.25 to Range 1.25 1.50 3.50 1.38 1.13 1.13 3.00 D = diopters; SD = standard deviation. Full-size table Table options View in workspace Download as CSV 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 3.0 D to 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 4presents 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 1week 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. Table 4. Predictability of Manifest Refraction Attempted vs. Achieved in Patients with an Implantable Contact Lens for Moderate to High Myopia 1 Week n/N 1 Month n/N 3 Months 6 Months 12 Months 24 Months (%) (%) n/N (%) n/N (%) n/N (%) n/N (%) 276/495 301/501 301/480 280/464 261/424 148/258 0.50 D (55.8%) (60.1%) (62.7%) (60.3%) (61.6%) (57.4%) 399/495 420/501 421/480 402/464 359/424 207/258 1.00 D (80.6%) (83.8%) (87.7%) (86.6%) (84.7%) (80.2%) 472/495 480/501 462/489 443/464 410/424 247/258 2.00 D (95.4%) (95.8%) (96.3%) (95.5%) (96.7%) (95.7%) Overcorrected 10/501 9/495 (1.8%) 7/480 (1.5%) 7/464 (1.5%) 4/424 (0.9%) 6/258 (2.3%) >+1 (2.0%) Overcorrected 4/495 (0.8%) 1/501 (0.2%) 1/480 (0.2%) 0/464 (0.0%) 0/424 (0.0%) 0/258 (0.0%) >+2 Undercorrected 87/495 71/501 52/480 55/464 61/424 45/258 (17.6%) (14.2%) (10.8%) (11.9%) (14.4%) (17.4%) <1 Undercorrected 19/495 20/501 17/480 21/464 14/424 (3.3%) 11/258 (4.3%) (3.8%) (4.0%) (3.5%) (4.5%) <2 Not reported 6 4 2 4 4 0 Total 501 505 482 468 428 258 D = diopters. Full-size table

Table options View in workspace Download as CSV 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 MRSE Table 5 contains predictability outcomes when study cohort eyes are stratified by their level of preoperative myopia into three MRSE groups: <7 D, 7 to 10 D, and >10 D. Table 5. Predictability of Manifest Refraction Attempted vs. Achieved Stratified by Dioptric Group in Patients with an Implantable Contact Lens for Moderate to High Myopia 6 Months n/N (%) 12 Months n/N (%) 24 Months n/N (%) Myopia Myopia Myopia Myopia Myopia Myopia Myopia Myopia Myopia <7 >10 <7 >10 <7 >10 710 710 710 diopters diopters diopters diopters diopters diopters diopters diopters diopters 67/87 120/162 93/215 63/84 103/149 95/191 32/40 62/94 54/124 0.50 D (77.0%) (74.1%) (43.3%) (75.0%) (69.1%) (49.7%) (80.0%) (66.0%) (43.5%) 85/87 151/162 166/215 81/84 137/149 141/191 38/40 84/94 85/124 1.00 D (97.7%) (93.2%) (77.2%) (96.4%) (91.9%) (73.8%) (95.0%) (89.4%) (68.5%) 87/87 161/162 194/215 84/84 148/149 178/191 40/40 94/94 113/124 2.00 D (100.0%) (99.4%) (90.2%) (100.0%) (99.3%) (93.2%) (100.0%) (100.0%) (91.1%) Overcorrected 0/87 2/162 5/215 0/84 3/149 1/191 0/40 4/94 2/124 >+1 (0.0%) (1.2%) (2.3%) (0.0%) (2.0%) (0.5%) (0.0%) (4.3%) (1.6%) Overcorrected 0/87 0/162 0/215 0/84 0/149 0/191 0/40 0/94 0/124 >+2 (0.0%) (0.0%) (0.0%) (0.0%) (0.0%) (0.0%) (0.0%) (0.0%) (0.0%) Undercorrected 2/87 9/162 44/215 3/84 9/149 49/191 2/40 6/94 37/124 (2.3%) (5.6%) (20.5%) (3.6%) (6.0%) (25.7%) (5.0%) (6.4%) (29.8%) <1 Undercorrected 0/87 1/162 21/215 0/84 1/149 13/191 0/40 0/94 11/124 (0.0%) (0.6%) (9.8%) (0.0%) (0.7%) (6.8%) (0.0%) (0.0%) (8.9%) <2 Not reported 1 3 0 2 1 1 0 0 0 Total 88 165 215 86 150 192 40 94 124 D = diopters. Full-size table Table options View in workspace Download as CSV 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% (710 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 BSCVA between 1 and 24 months postoperatively (Table 6). This 42-year-old female with 12.75 D myopia inadvertently received a carbachol solution containing preservative irrigated intracamerally at the end of ICL surgery instead of the intended preservative-free carbachol. She had transient corneal edema, which subsequently cleared, and vacuoles were noted in the AS region 2 <img height="35" border="0" style="vertical-align:bottom" width="11" alt="View the MathML source" title="View the MathML source" src="http://origin-ars.els-cdn.com/content/image/1-s2.0-S0161642002017712-si1.gif"> 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. Table 6. Change in Best Spectacle-corrected Visual Acuity in Patients with an Implantable Contact Lens for Moderate to High Myopia 1 Week n/N 1 Month n/N 3 Months n/N 6 Months n/N 12 Months n/N 24 Months n/N (%) (%) (%) (%) (%) (%) Decrease >2 3/498 (0.6%) 0/501 (0.0%) 0/481 (0.0%) 0/464 (0.0%) 0/427 (0.0%) 1/257 (0.4%) lines Decrease 2 6/498 (1.2%) 3/501 (0.6%) 1/481 (0.2%) 2/464 (0.4%) 3/427 (0.7%) 3/257 (1.2%) lines Decrease 1 56/498 33/501 18/481 (3.7%) 19/464 (4.1%) 23/427 (5.4%) 20/257 (7.8%) line (11.2%) (6.6%) 252/498 248/501 221/481 218/464 189/427 106/257 No change (50.6%) (49.5%) (45.9%) (47.0%) (44.3%) (41.2%) 137/498 163/501 189/481 170/464 171/427 99/257 Increase 1 line (27.5%) (32.5%) (39.3%) (36.6%) (40.0%) (38.5%) Increase 2 30/498 37/501 39/481 (8.1%) 41/464 (8.8%) 30/427 (7.0%) 19/257 (7.4%) lines (6.0%) (7.4%) Increase >2 14/498 17/501 13/481 (2.7%) 14/464 (3.0%) 11/427 (2.6%) 9/257 (3.5%) lines (2.8%) (3.4%) Mean change 0.33 0.50 0.60 0.59 0.56 0.53 Not reported 3 4 1 4 1 1 Total 501 505 482 468 428 258 Full-size table Table options View in workspace Download as CSV 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. Table 7. Postoperative Complications in Patients with an Implantable Contact Lens for Moderate to High Myopia 1 Day 1 Week 1 Month 3 Months 6 Months 12 Months 24 Months n/N (%) 101/52 (19.3% 3 ) (11.3% 59/523 ) n/N 6/50 1 2/50 1 0/50 (0.0%) 1 0/50 (0.2%) 1 (0.0%) (%) (1.2% ) (0.4% ) (0.0% ) (0.0% ) n/N 0/50 5 0/50 5 0/50 5 0/50 5 (%) (0.0% ) (0.0% ) (0.0% ) (0.0% ) n/N 0/48 2 0/48 2 0/48 2 0/48 2 (%) (0.0% ) (0.0% ) (0.0% ) (0.0% ) n/N 0/46 8 0/46 8 1/46 8 0/46 8 (%) (0.0% ) (0.0% ) (0.2% ) (0.0% ) n/N 0/42 8 0/42 8 0/42 8 0/42 8 (%) (0.0% ) (0.0% ) (0.0% ) (0.0% ) n/N 0/25 8 0/25 8 0/25 8 0/25 8 (%) (0.0% ) (0.0% ) (0.0% ) (0.0% )

Iritis

Corneal edema Retinal 0/523 detachment Iris prolapse 1/523 repair Treatment of acute 0/523 retinal hole Attempted argon laser 0/523 synechiolysi s n/N = Full-size table

0/50 (0.0% 0/50 (0.0% 1/48 (0.2% 0/46 (0.0% 0/42 (0.0% 0/25 (0.0% 1 ) 5 ) 2 ) 8 ) 8 ) 8 ) 0/50 (0.0% 0/50 (0.0% 0/48 (0.0% 1/46 (0.2% 0/42 (0.0% 0/25 (0.0% 1 ) 5 ) 2 ) 8 ) 8 ) 8 )

(0.0%)

Table options View in workspace Download as CSV 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 yttriumaluminumgarnet 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 patients 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. 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 8presents 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. Table 8. Distribution of Lens Opacity Classification System III Scores Over Time in Patients with an Implantable Contact Lens for Moderate to High Myopia Preoperativ 1 Week 1 Month 3 Months 6 Months 12 Months 24 Months e n/N Nuclear color (77.8 388/5 %) 01 Trace (22.0 112/5 (0.5) %) 01 (0.0% Mild (1) 0/523 0/501 ) Moderat (0.2% e (1.5 to 1/523 1/501 ) 2) Marked (0.0% 0/523 0/501 (>2) ) Nuclear Opalesce nce 400/5 (76.5 386/5 Clear (0) 23 %) 01 Trace 119/5 (22.8 112/5 Clear (0) 407/5 23 115/5 23 (77.4 388/5 %) 04 (22.4 115/5 %) 04 (0.0% 0/504 ) (77.0 368/4 %) 81 (22.8 112/4 %) 81 (0.0% 0/481 ) (76.5 359/4 %) 68 (23.3 108/4 %) 68 (0.0% 0/468 ) (76.7 322/4 %) 26 (23.1 103/4 %) 25 (0.0% 0/426 ) (75.6 %) (24.2 %) 163/2 57 93/25 7 (63.4 %) (36.2 %) (%) n/N (%) n/N (%) n/N (%) n/N (%) n/N (%) n/N (%)

(0.0%) 0/257 (0.0%)

(0.2% (0.2% (0.2% (0.2% 1/504 1/481 1/468 1/426 (0.2%) 1/257 (0.4%) ) ) ) ) (0.0% (0.0% (0.0% (0.0% 0/504 0/481 0/468 0/426 (0.0%) 0/257 (0.0%) ) ) ) )

(77.0 386/5 (76.6 370/4 (76.9 360/4 (76.9 329/4 (77.2 165/2 (64.2 %) 04 %) 81 %) 68 %) 26 %) 57 %) (22.4 115/5 (22.8 108/4 (22.5 105/4 (22.4 95/42 (22.3 91/25 (35.4

Preoperativ 1 Week e (%) n/N (0.5) %) 01 (0.6% Mild (1) 3/523 2/501 ) Moderat (0.2% e (1.5 to 1/523 1/501 ) 2) Marked (0.0% 0/523 0/501 (>2) ) Cortical 495/5 (94.6 491/5 Clear (0) 23 %) 01 Trace 26/52 (5.0% 9/501 (0.5) 3 ) (0.2% Mild (1) 1/523 1/501 ) Moderat (0.2% e (1.5 to 1/523 0/501 ) 2) Marked (0.0% 0/523 0/501 (>2) ) Posterior subcapsu lar 519/5 (99.2 499/5 Clear (0) 23 %) 01 Trace (0.8% 4/523 2/501 (0.5) ) (0.0% Mild (1) 0/523 0/501 ) Moderat (0.0% e (1.5 to 0/523 0/501 ) 2) Marked (0.0% 0/523 0/501 (>2) ) Anterior Subcapsu lar 519/5 (99.2 475/5 Clear (0) 23 %) 01 Trace (0.8% 21/50 4/523 (0.5) ) 1 (0.0% Mild (1) 0/523 3/501 ) n/N 23

1 Month

3 Months

6 Months

12 Months

24 Months

(%) n/N %) 04 (0.4% 2/504 )

(%) n/N %) 81 (0.4% 2/481 )

(%) n/N %) 68 (0.4% 2/468 )

(%) n/N (%) n/N (%) %) 6 %) 7 %) (0.4% 1/426 (0.2%) 0/257 (0.0%) )

(0.2% (0.2% (0.2% (0.2% 1/504 1/481 1/468 1/426 (0.2%) 1/257 (0.4%) ) ) ) ) (0.0% (0.0% (0.0% (0.0% 0/504 0/481 0/468 0/426 (0.0%) 0/257 (0.0%) ) ) ) ) (98.0 495/5 %) 04 (1.8% 8/504 ) (0.2% 1/504 ) (98.2 473/4 %) 81 (1.6% 7/481 ) (0.2% 0/481 ) (98.3 459/4 %) 68 (1.5% 7/468 ) (0.0% 1/468 ) (98.1 417/4 %) 26 (1.5% 8/426 ) (0.2% 1/426 ) (97.9 257/2 (100.0 %) 57 %) (1.9%) 0/257 (0.0%) (0.2%) 0/257 (0.0%)

(0.0% (0.0% (0.2% (0.2% 0/504 1/481 1/468 0/426 (0.0%) 0/257 (0.0%) ) ) ) ) (0.0% (0.0% (0.0% (0.0% 0/504 0/481 0/468 0/426 (0.0%) 0/257 (0.0%) ) ) ) )

(99.6 502/5 %) 04 (0.4% 2/504 ) (0.0% 0/504 )

(99.6 480/4 %) 81 (0.4% 1/481 ) (0.0% 0/481 )

(99.8 467/4 %) 68 (0.2% 1/468 ) (0.0% 0/468 )

(99.8 426/4 %) 26 (0.2% 0/426 ) (0.0% 0/426 )

(100.0 257/2 (100.0 %) 57 %) (0.0%) 0/257 (0.0%) (0.0%) 0/257 (0.0%)

(0.0% (0.0% (0.0% (0.0% 0/504 0/481 0/468 0/426 (0.0%) 0/257 (0.0%) ) ) ) ) (0.0% (0.0% (0.0% (0.0% 0/504 0/481 0/468 0/426 (0.0%) 0/257 (0.0%) ) ) ) )

(94.8 482/5 %) 04 (4.2% 17/50 ) 4 (0.6% 2/504 )

(95.6 459/4 %) 81 (3.4% 18/48 ) 1 (0.4% 2/481 )

(95.4 447/4 %) 68 (3.75 15/46 %) 8 (0.4% 4/468 )

(95.5 398/4 %) 26 (3.2% 22/42 ) 6 (0.9% 2/426 )

(93.4 238/2 (92.6 %) 57 %) 13/25 (5.2%) (5.1%) 7 (0.5%) 4/257 (1.6%)

Preoperativ 1 Week e n/N (%) n/N (%)

1 Month n/N (%)

3 Months n/N (%)

6 Months n/N (%)

12 Months n/N (%)

24 Months n/N (%)

Moderat (0.0% e (1.5 to 0/523 2/501 ) 2) Marked (0.0% 0/523 0/501 (>2) )

(0.4% (0.6% (0.4% (0.4% 3/504 2/481 2/468 4/426 (0.5%) 2/257 (0.8%) ) ) ) ) (0.0% (0.0% (0.0% (0.0% 0/504 0/481 0/468 0/426 (0.0%) 0/257 (0.0%) ) ) ) )

n/N = Full-size table Table options View in workspace Download as CSV 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 surgeons 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 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 Table 9. Change in Subjective Patient Symptoms (Preoperative to 12-month Postoperative in Patients with an Implantable Contact Lens for Moderate to High Myopia) Quality of Vision Glare Haloes Double Vision Night Driving n Improved 2 categories 23 % (5.7%) n % n % n 10 (2.5%) 12 (2.9%) 2 % (0.5%) n % 17 (4.3%)

Quality of Vision Glare

Haloes

Double Vision Night Driving

n % n % n % n % n % 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%) Full-size table Table options View in workspace Download as CSV Discussion The 12-month clinical outcomes presented in this report from the ongoing U. S. FDA ICL Clinical Study for Myopia 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 Myopia 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.32, 33, 34, 35, 36, 37, 38, 39, 40 and 42 Table 10summarizes 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 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 U.S. Food and Drug Parameter LaserSight Nidek Autonomous Administration Implantable Contact Photorefractive Photorefractive Photorefractive Procedure Lens Keratectomy Keratectomy Keratectomy 7.0 to 13.00 D 7.0 to 10.0 D Myopia range (D) 3.0 to 20.0 D SE 6.0 to 10.0 D SE SE sphere Mean preoperative NR NR NR 10.05 3.75 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 61.6% (12 mos) 32.5% (6 mos) 42.8% (6 mos) 60.0% (6 mos) 0.50 D 35.0% (12 mos) 84.7% (12 mos) 52.6% (6 mos) 68.3% (6 mos) 76.7% (6 mos) 1.0 D 60.0% (12 mos) 96.7% (12 mos) 90.4% (6 mos) 86.2% (6 mos) NR 2.0 D 86.7% (12 mos) UCVA 67.0% (6 mos) 80.7% (6 mos) 86.2% (6 mos) 20/40 or better 92.5% (12 mos) 69.1% (12 mos)

U.S. Food and Drug Administration Implantable Contact Procedure Lens 20/20 or better 60.1% (12 mos) Parameter Loss of BSCVA > 2 lines

LaserSight Photorefractive Keratectomy 32.1% (6 mos) 21.9% (12 mos)

Nidek Photorefractive Keratectomy 45.5% (6 mos)

Autonomous Photorefractive Keratectomy 48.3% (6 mos)

0.9% (6 mos) 3.5% (6 mos) NR 3.3% (12 mos) BSCVA = best spectacle-corrected visual acuity; D = diopter; SE = spherical equivalent; NR = not reported; UCVA = uncorrected visual acuity. Best spectacle-corrected visual acuity 20/20 or better preoperative. * Sphere only eyes. Full-size table Table options View in workspace Download as CSV Table 11summarizes 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 (>6 or >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. Table 11. Comparison of U.S. Implantable Contact Lens Study to U.S. Food and Drug AdministrationApproved LASIK U.S. Food and Drug Parameter Nidek Autonomous Administration Implantable Contact Laser In Situ Procedure Laser In Situ Keratomileusis Lens Keratomileusis >7.0 to 20.0 D sphere 7.0 to 11.0 D sphere Myopia range (D) 3.0 to 20.0 D SE 4.0 D cyl 0.50 to <6.0 D cyl Mean preoperative NR NR 10.05 D 3.75 D myopia (D) Follow-up 12 mos 6 and 12 mos 3 mos Number of cases 523 eyes 1126 eyes 177 eyes* Predictability 61.6% (12 mos) 64.5% (12 mos) NR 0.50 D 84.7% (12 mos) 73.3% (6 mos) 86.4% (3 mos) 1.0 D 77.2% (12 mos) 96.7% (12 mos) 92.7% (6 mos) 100% (3 mos) 2.0 D 94.4% (12 mos) UCVA 92.5% (12 mos) NR 85.7% (3 mos) 20/40 or better 60.1% (12 mos) NR 71.4% (3 mos) 20/20 or better Loss of BSCVA > 2 lines 0.2% (12 mos) NR 4.5% (3 mos)

0.2% (12 mos)

BSCVA = best spectacle-corrected visual acuity; D = diopters; NR = not reported; SE = spherical equivalent; UCVA = uncorrected visual acuity. * Sphere only eyes. Best spectacle-corrected visual acuity 20/20 or better preoperative. Full-size table Table options View in workspace Download as CSV 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 al19 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 (0.2%) lost more than 2 lines at any postoperative visit through 24 months, a result of a cataract caused by preservativecontaining 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 al24 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 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 and 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 yttriumaluminumgarnet 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 and 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 surgeons 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 population. 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 myopia 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 20.00 D and a highest lens power of 20.00 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 10.31 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 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. Appendix. The Implantable Contact Lens for Myopia (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,* and 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 References 1 J.H. Kim, T.W. Hahn, Y.C. Lee, W.J. Sah Excimer laser photorefractive keratectomy for myopiatwo year follow-up J Cataract Refract Surg, 20 (Suppl) (1994), pp. S229233 [SD-008] 2 E. Maguen, J.J. Salz, A.B. Nesburn et al. Results of excimer laser photorefractive keratectomy for the correction of myopia Ophthalmology, 101 (1994), pp. 15481556 discussion 15567 [SD-008] 3

J. Pietil, P. Mkinen, S. Pajari et al. Photorefractive keratectomy for 1.25 to 25.00 diopters of myopia J Refract Surg, 14 (1998), pp. 615622 [SD-008] 4 J. Heitzmann, P.S. Binder, B.S. Kassar, L.T. Nordan The correction of high myopia using the excimer laser Arch Ophthalmol, 111 (1993), pp. 16271634 [SD-008] 5 T. Seiler, A. Holschbach, M. Derse et al. Complications of myopic photorefractive keratectomy with the excimer laser Ophthalmology, 101 (1994), pp. 153160 [SD-008] 6 P.S. Hersh, R.F. Steinert, S.F. Brint Photorefractive keratectomy versus laser in situ keratomileusiscomparison of optical side effects. Summit PRKLASIK Study Group Ophthalmology, 107 (2000), pp. 925933 [SD-008] 7 J.T. Holladay, D.R. Dudeja, J. Chang Functional vision and corneal changes after laser in situ keratomileusis determined by contrast sensitivity, glare testing, and corneal topography J Cataract Refract Surg, 25 (1999), pp. 663669 [SD-008] 8 C.K. Joo, T.G. Kim Corneal perforation during laser in situ keratomileusis J Cataract Refract Surg, 25 (1999), pp. 11651167 [SD-008] 9 F.J. Goes Photorefractive keratectomy for myopia of 8.00 to 24.00 diopters J Refract Surg, 12 (1996), pp. 9197 [SD-008] 10 J.M. Davidorf, R. Zaldivar, S. Oscherow Results and complications of laser in situ keratomileusis by experienced surgeons J Refract Surg, 14 (1998), pp. 114122 [SD-008]

11 S.P. Holland, S. Srivannaboon, D.Z. Reinstein Avoiding serious corneal complications of laser assisted in situ keratomileusis and photorefractive keratectomy Ophthalmology, 107 (2000), pp. 640652 [SD-008] 12 H.S. Geggel, A.R. Talley Delayed onset keratectasia following laser in situ keratomileusis J Cataract Refract Surg, 25 (1999), pp. 582586 [SD-008] 13 R.J. Tsai Laser in situ keratomileusis for myopia of 2 to 25 diopters J Refract Surg, 13 (1997), pp. S427429 [SD-008] 14 M.C. Knorz, A. Liermann, V. Seiberth et al. Laser in situ keratomileusis to correct myopia of 6.00 to 29.00 diopters J Refract Surg, 12 (1996), pp. 575584 [SD-008] 15 M.N. Shah, M. Misra, K.R. Wihelmus, D.D. Koch Diffuse lamellar keratitis associated with epithelial defects after laser in situ keratomileusis J Cataract Refract Surg, 26 (2000), pp. 13121318 [SD-008] 16 G. Baikoff, J.L. Arne, Y. Bokobza et al. Angle-fixated anterior chamber phakic intraocular lens for myopia of 7 to 19 diopters J Refract Surg, 14 (1998), pp. 282293 [SD-008] 17 S.N. Fyodorov, V.K. Zuev, E.R. Tumanyan et al. Analysis of long term clinical and functional results of intraocular correction of high myopia Ophthalmosurgery (Moscow), 2 (1990), pp. 36 [SD-008] 18 J.L. Menezo, A. Cisneros, J.R. Hueso, M. Harto Long-term results of surgical treatment of high myopia with Worst-Fechner intraocular lenses J Cataract Refract Surg, 21 (1995), pp. 9398 [SD-008] 19

D.R. Sanders, D.C. Brown, R.G. Martin et al. Implantable contact lens for moderate to high myopiaphase I FDA clinical study with 6 month follow-up J Cataract Refract Surg, 24 (1998), pp. 607611 [SD-008] 20 J.L. Arne, L.C. Lesueur Phakic posterior chamber lenses for high myopiafunctional and anatomical outcomes J Cataract Refract Surg, 26 (2000), pp. 369374 [SD-008] 21 M. Gonvers, P. Othenin-Girard, C. Bornet, M. Sickenberg Implantable contact lens for moderate to high myopiashort-term follow-up of 2 models J Cataract Refract Surg, 27 (2001), pp. 380388 [SD-008] 22 J.L. Menezo, C. Peris-Martnez, A. Cisneros, R. Martnez-Costa Posterior chamber phakic intraocular lenses to correct high myopiaa comparative study between Staar and Adatomed models J Refract Surg, 17 (2001), pp. 3242 [SD-008] 23 P.M. Pesando, M.P. Ghiringhello, P. Tagliavacche Posterior chamber collamer phakic intraocular lens for myopia and hyperopia J Refract Surg, 15 (1999), pp. 415423 [SD-008] 24 V. Assetto, S. Benedetti, P. Pesando Collamer intraocular contact lens to correct high myopia J Cataract Refract Surg, 22 (1996), pp. 551556 [SD-008] 25 R. Zaldivar, J.M. Davidorf, S. Oscherow Posterior chamber phakic intraocular lens for myopia of 8 to 19 diopters J Refract Surg, 14 (1998), pp. 294305 [SD-008] 26 D. BenEzra, E. Cohen, I. Karshai Phakic posterior chamber intraocular lens for the correction of anisometropia and treatment of amblyopia Am J Ophthalmol, 130 (2000), pp. 292296 [SD-008] 27

I. Jimenez-Alfaro, J.M. Benitez del Castillo, J. Garcia-Feijoo et al. Safety of posterior chamber phakic intraocular lenses for the correction of high myopiaanterior segment changes after posterior chamber phakic intraocular lens implantation Ophthalmology, 108 (2001), pp. 9099 [SD-008] 28 V. Kaya, M.A. Kevser, O.F. Yilmaz Phakic posterior chamber plate intraocular lenses for high myopia J Refract Surg, 15 (1999), pp. 580585 [SD-008] 29 E. Rosen, C. Gore Staar Collamer posterior chamber phakic intraocular lens to correct myopia and hyperopia J Cataract Refract Surg, 24 (1998), pp. 596606 [SD-008] 30 C.A. Snchez-Galeana, R.J. Smith, X. Rodriguez et al. Laser in situ keratomileusis and photorefractive keratectomy for residual refractive error after phakic intraocular lens implantation J Refract Surg, 17 (2001), pp. 299304 [SD-008] 31 L.T. Chylack Jr, J.K. Wolfe, D.M. Singer et al. The Lens Opacities Classification System III. The Longitudinal Study Of Cataract Study Group Arch Ophthalmol, 111 (1993), pp. 831836 [SD-008] 32 F. Trindade, F. Pereira Cataract formation after posterior chamber phakic intraocular lens implantation J Cataract Refract Surg, 24 (1999), pp. 16611663 [SD-008] 33 Autonomous Technologies Corporation LADARVision Excimer Laser System-P970043. Summary of Safety and Effectiveness DataCenter for Devices and Radiological Health, Rockville, MD (1998) [SD-008] 34 LaserSight Technologies, Inc Summary of Safety and Effectiveness Data. LaserScan LSX Excimer Laser System for photorefractive keratectomy for myopia-P980008Center for Devices and Radiological Health, Rockville, MD (1999) [SD-008] 35

Nidek Technologies Inc Nidek EC-5000 Excimer Laser System-P970053. Summary of Safety and Effectiveness DataCenters for Devices and Radiological Health, Rockville, MD (1998) [SD-008] 36 Nidek Technologies, Inc Nidek EC-5000 Excimer Laser System for Photorefractive Keratectomy for Moderate Myopia with AsgigmatismP970053/5001. Summary of Safety and Effectiveness Data for a Supplemental Premarket Approval (PMA) ApplicationCenter for Devices and Radiological Health, Rockville, MD (2000) [SD-008] 37 Autonomous Technologies Corporation LADARVision Excimer Laser System-P970043/S005. Summary of Safety and Effectiveness Data for a Supplemental Premarket Approval Application (PMA) ApplicationCenter for Devices and Radiological Health, Rockville, MD (2000) [SD-008] 38 J.G. Dishler Dishler Excimer Laser System-P970049. Summary of Safety and Effectiveness DataCenter for Devices and Radiological Health, Rockville MD (1999) [SD-008] 39 Photomed, Inc Kremer Excimer Laser System Serial No. KEA940202 for Laser In Situ Keratomileusis (LASIK) for the Correction of Primary Myopia, with and Without Astigmatism-P970005. Summary of Safety and Effectiveness DataCenter for Devices and Radiological Health, Rockville, MD (1999) [SD-008] 40 Summit Technology, Inc SVS Apex Plus Excimer Laser Workstation emphasis M discs-P930034/S013. Summary of Safety and Effectiveness Data for a Supplemental Premarket Approval ApplicationCenter for Devices and Radiological Health, Rockville, MD (1999) [SD-008] 41 A.M. Fink, C. Gore, E. Rosen Cataract development after implantation of the Staar Collamer posterior chamber phakic lens J Cataract Refract Surg, 25 (1999), pp. 278282 [SD-008] 42 CRS Clinical Research, Inc VISX STAR S2 Excimer Laser System-P990010. Summary of Safety and Effectiveness DataCenter for Devices and Radiological Health, Rockville, MD (1999) [SD-008]

 Manuscript no. 210619. Supported by STAAR Surgical, Monrovia, California. <img border="0" alt="Corresponding author contact information" title="Corresponding author conact information" src="http://origin-cdn.els-cdn.com/sd/entities/REcor.gif"> Reprints requests to Darcy Smith, STAAR Surgical Company, 1911 Walker Avenue, Monrovia, CA 91016, USA. * The Appendix lists participants of the Study Group. * 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. Copyright 2003 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.