Intrastromal corneal ring segments for low myopia

Ophthalmic Technology Assessment

Intrastromal Corneal Ring Segments for Low Myopia A Report by the American Academy of Ophthalmology Christopher J. Rapuano, MD, Alan Sugar, MD, MS, Douglas D. Koch, MD, Peter J. Agapitos, MD, William W. Culbertson, MD, Vincent P. de Luise, MD, David Huang, MD, PhD, Gary A. Varley, MD Objective: This document describes intrastromal corneal ring segments (Intacs) inserts technology and examines the evidence to answer the key question about whether the treatment is safe and effective in correcting low myopia. Methods: A literature search that was conducted in September 2000 retrieved 13 relevant citations, and the reference lists of these articles were consulted for additional citations. Panel members reviewed this information and articles were rated according to the strength of evidence. Results: Prospective multicenter phase II and III clinical trials (Level II evidence rating) of Intacs inserts for myopia of ⫺1.00 to ⫺3.00 diopters (D), with a maximum of ⫹1.00 D of astigmatism, enrolled a total of 452 subjects, with a total of 454 surgical attempts. The results from phase II and phase III were pooled for much of the analysis. At 1 year, 97% of patients who completed follow-up had 20/40 or better uncorrected visual acuity (UCVA). Seventy-four percent of patients had 20/20 or better UCVA. Ninety-two percent of eyes were within ⫾1 D of intended refractive correction, and 69% were within 0.5 D of intended refractive correction. At 3 months, 90% of patients had less than 1.0 D of change from the previous examination performed at 1 month. The ocular complication rate, which was defined as clinically significant events but not resulting in permanent sequelae, was 11% at 12 months. The adverse event rate was 1.1%, defined as a serious event if untreated. Nearly 9% of patients requested to have their inserts removed and a total of 3.8% of patients required a secondary surgical intervention. Conclusions: To date, evidence suggests that low myopia (⫺1 to ⫺3 D) in a well-defined group of patients who have a stable manifest refraction and less than ⫹1.0 D of astigmatism can be treated with Intacs inserts with a reasonable assurance of safety and effectiveness. Additional clinical research is needed to determine the long-term effectiveness of treatment and the comparative safety, effectiveness, and costs with other treatment modalities, including laser-assisted in-situ keratomileusis (LASIK) and photorefractive keratectomy (PRK). Ophthalmology 2001;108:1922–1928 © 2001 by the American Academy of Ophthalmology. The American Academy of Ophthalmology (AAO) prepares Ophthalmic Technology Assessments (OTA) to evaluate new and existing procedures, drugs, and diagnostic and screening tests. The goal of an OTA is to evaluate the peer-reviewed published scientific literature, to distill what is well established about the technology, and to help refine the important questions to be answered by future investigations. After appropriate review by all contributors, including legal counsel, assessments are submitted to the Academy’s Board of Trustees for consideration as official Academy statements.

Originally received and accepted: June 22, 2001. Manuscript no. 210433. Prepared by the Ophthalmic Technology Assessment Committee Refractive Surgery Panel and approved by the American Academy of Ophthalmology’s Board of Trustees June 10, 2001.

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© 2001 by the American Academy of Ophthalmology Published by Elsevier Science Inc.

Background In 1949, Barraquer first tried to implant material in the cornea to correct refractive errors.1 Since that time, many materials have been assessed for their biocompatibility. In 1978, Reynolds conceived of an implantable corneal 360° ring for correcting myopic and hyperopic refractive errors.2 In July 1991, phase I of human clinical studies were initiated on nonsighted eyes.3 A 330° polymethyl methacrylate (PMMA) intrastromal ring was developed to correct myopia by flattening the central cornea in a predictable fashion, but placement of this ring was difficult. The device serves as a spacer between the corneal lamellae bundles, which results in a shortening of the corneal arc length of these fibers [Silvestrini TA, Mathis ML, Loomas BE, Burris TE. A geometric model to predict the change in corneal curvature from the intrastromal corneal ring (ICR). Invest Ophthalmol Vis Sci 1994;35(suppl):2023]. This shortening is proporISSN 0161-6420/01/$–see front matter PII S0161-6420(01)00804-1

American Academy of Ophthalmology 䡠 Ophthalmic Technology Assessment tional to the thickness of the ring, with an increased thickness resulting in greater degrees of correction.3 A 2-year phase II trial for this device was initiated in May 1995.4 Theoretical advantages of this technology over other keratorefractive procedures such as laser-assisted in situ keratomileusis (LASIK) and photorefractive keratectomy (PRK) include the ability to remove the device and potentially to reverse treatment effects, to revise correction by varying the thickness of the device, and to avoid ablation of central corneal tissue.5 The design of the full-ring (KeraVision ICR, Fremont, CA) product was subsequently modified to facilitate its placement and is currently comprised of two 150° crescent-shaped inserts. The microthin prescription Intacs inserts are surgically placed between corneal lamellae into the midperipheral cornea via a 1.2 mm incision.

Description of the Procedure Patients undergoing placement of Intacs inserts receive topical anesthesia. The surgeon marks the geometric center of the cornea and measures corneal thickness at the site of the planned incision. An incision, 1.2 mm in length and 68% of the corneal thickness, is made with a diamond blade at the 12 o’clock position, approximately 2.0 mm from the limbus. A centering guide is placed on the globe with a vacuum, and a lamellar dissector is introduced at the incision and rotated to create an intrastromal channel in each direction. It is recommended that these two channels be distinct to avoid segment contact. One segment is inserted into each channel, and one suture may be used to close the original incision. Three different thickness inserts, 0.25, 0.30 and 0.35 mm, are currently commercially available in the United States. The nomogram for Intacs inserts selection is as follows: ⫺1.0 to ⫺1.625 diopters (D) is the recommended prescribing range for a 0.25 mm thickness, ⫺1.75 to ⫺2.25 D is the recommended prescribing range for a 0.30 mm thickness, and ⫺2.375 to ⫺3.0 D is the recommended prescribing range for a 0.35 mm thickness. After placement, patients receive steroid and antibiotic treatment over a period of several days to a few weeks. Many patients wear a bandage contact lens for 1 to 3 days postoperatively.

FDA Status Intacs inserts technology was developed by KeraVision Inc. (Fremont, CA) and was approved for sale in the United States by the U.S. Food and Drug Administration (FDA) in April 1999. The indications are for use in adults 21 years and older who have mild myopia (⫺1.00 to ⫺3.00 D of spherical equivalent at the spectacle plane) with mild astigmatism (⫹1.00 D or less) and whose vision has been stable for the past year, as demonstrated by a change of ⱕ0.50 D for at least 12 months before the preoperative examination. Placement of Intacs inserts is contraindicated in patients with collagen vascular, autoimmune, or immunodeficiency diseases; in pregnant or nursing women; and in patients with ocular conditions such as keratoconus, recurrent corneal erosion syndrome, or corneal dystrophy that may predispose to future complications. It is also contraindicated in patients who are taking one or more of the following medications:

isotretinoin, amiodarone, and sumatriptan. Labeling by the FDA also states that Intacs inserts are not recommended for placement in patients with systemic diseases that are likely to affect wound healing, such as severe atopic disease or insulin-dependent diabetes or in patients who have a history of ophthalmic Herpes simplex or Herpes zoster. The labeling includes several other precautions. Patients who receive the 0.35 mm Intacs inserts may experience a poorer outcome than patients who receive the 0.25 mm or 0.30 mm Intacs inserts and an increased removal rate due to dissatisfaction with their outcomes. Patients with myopia of ⫺1.00 D are more likely to be overcorrected. The long-term effect of Intacs inserts on endothelial cell density has not been established. A temporary decrease in central corneal sensation has been noted in some patients. Some patients with large dilated pupil diameters (ⱖ7.0 mm) are predisposed to low-light visual symptoms postoperatively and should be appropriately advised. Under mesopic conditions (intermediate levels of illumination), patients may experience some loss in contrast sensitivity at low spatial frequencies (1.5 cycles per degree). The safety and effectiveness of alternate refractive procedures following the removal of Intacs inserts have not been established. The safety and effectiveness of Intacs inserts also has not been established for the following situations: myopia greater than ⫺3.5 D or astigmatism greater than ⫹1.00 D, corneas steeper than 46 D or flatter than 40 D, corneas with central thickness less than 480 ␮m or with peripheral thickness less than 570 ␮m, or progressive myopia, progressive astigmatism, nuclear sclerosis, crystalline lens opacity, corneal abnormality, previous corneal surgery or trauma, longterm use, or for patients under 21 years of age. At the FDA’s request, KeraVision was conducting a postapproval study to assess the effects of the device on the corneal endothelium 2 or more years after placement. However, on March 23, 2001, the company filed chapter 11 bankruptcy, and has since sold substantially all its assets to Addition Technology Inc. (Fremont, CA).

Resource Requirements The Intacs inserts technology includes a surgical instrument set that is retail priced at $36,000 and the Intacs inserts that are retail priced at $500 each. Physicians are required to complete a full-day KeraVision-approved training course and proctoring for the first five cases, and to read and understand a KeraVision Surgeon Training Manual. KeraVision provides various financing options. The costs for refractive procedures, including PRK, LASIK, and Intacs inserts, vary widely across the country, ranging from $500 to $2500/eye. The time for surgery can vary from 10 minutes to 30 minutes, depending on the surgeon’s experience and the type of procedure being performed.

Question for Assessment The key question that is the focus of this assessment is as follows:

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Ophthalmology Volume 108, Number 10, October 2001 ● Is intrastromal corneal ring segments technology safe and effective in treating low myopic refractive errors (⫺1.0 to ⫺3.0 D)?

Description of Evidence The literature search that was conducted in September 2000 consisted of a text word search in MEDLINE for the years 1990 to 2000. The terms intracorneal or intrastromal corneal ring and Intacs inserts were used, and results were limited to articles in English. The reference lists of these articles were consulted for additional citations. The search methodology included contacting ophthalmic professional organizations and industry to identify additional articles or data. This information was reviewed by panel members and a methodologist, who assigned a rating to each study as follows. Level I is assigned to properly conducted, well-designed randomized clinical trials; Level II is assigned to welldesigned cohort and case-control studies; and Level III is assigned to case series. Members of the Ophthalmic Technology Assessment Committee and other AAO committees reviewed drafts of this document before formal approval by the Board of Trustees. The published literature contains a report of some of the results from a phase III clinical trial, which was a prospective, nonrandomized multicenter study that was assigned a Level II rating. Other studies reported on specific aspects of the outcomes using Intacs inserts and were assigned a Level II rating. Quality of life assessments were not performed. Abstracts from presentations at meetings are not subject to peer review and were not included in the analysis.

Published Results Prospective, multicenter phase II and III clinical trials of Intacs inserts for myopia of ⫺1.00 to ⫺3.00 D enrolled a total of 452 subjects, with a total of 454 surgical attempts. (Two subjects had the Intacs inserts device implanted in the fellow eye after unsuccessful initial surgery.)6 Because the study protocols for the phase II (90 patients at six sites) and phase III trials (362 patients at 10 sites) were very similar, results were pooled together for much of the analysis by the FDA. Strict eligibility criteria for the study included myopia in the range of ⫺1.00 to ⫺3.50 D with ⫹1.00 D or less of astigmatism, a stable manifest refraction of 1.00 D or less change within the previous 6 months, and best spectaclecorrected visual acuity (BSCVA) of 20/20 or better in both eyes. Criteria also included a corneal diameter greater than 10 mm and corneal curvature greater than 40 D and less than 46 D. If there were a central corneal thickness of less than 480 ␮m or a peripheral corneal thickness of less than 570 ␮m, patients were excluded. Patients were also excluded if they had active ocular disease likely to affect wound healing, history of glaucoma, irregular astigmatism, herpetic eye disease, significant corneal abnormalities, evidence of retinal vascular disease or history of hypercoagulability, abnormal tear status, diabetes, connective tissue

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disease, immunocompromised status, history of acute or chronic disease or prior ophthalmic surgery, or if they used systemic medications likely to affect wound healing. Of the entire group receiving Intacs inserts, 51% were female, 83% were white, and the mean age was 39.4 years. Forty-three percent of patients had a preoperative uncorrected visual acuity (UCVA) of 20/125 or worse, 44% had a preoperative UCVA of 20/50 to 20/100, and 12% had a UCVA of 20/25 to 20/40. A total of 447 implants were successfully placed in 452 subjects in the first attempt. In 4 subjects, the Intacs inserts were not successfully placed because of intraoperative complications such as corneal surface perforation (n ⫽ 3) and chemosis (n ⫽ 1). In 2 subjects, the implant was then successfully placed in the contralateral eye. At 1 year, 39 subjects did not have an examination. This left a total of 410 of 449 subjects with initial implants who were examined at 1 year (91% follow-up of initial subjects). At 1 year, 97% of patients who completed a follow-up examination had 20/40 or better UCVA, and 74% had 20/20 or better UCVA. Ninety-two percent of eyes were within ⫾1 D of intended refractive correction, and 69% were within ⫾0.5 D of intended refractive correction. At 3 months, 90% of patients had ⱕ1.0 D change from the previous examination at month 1, and at 6 months 97% of patients had ⱕ1.0 D change from month 3. Ocular complications were defined as findings that had the potential to be clinically significant but not resulting in vision loss or permanent sequelae. The findings at 12 months included reduction of central corneal sensation of ⱖ20 mm (5.5%), induced cylinder ⬎1 to 2 D (3.7%), deep neovascularization (1.2%), loss of more than two lines of BSCVA (1.0%), persistent epithelial defect (0.2%), and iritis/uveitis (0.2%). Deep neovascularization was limited to the incision site and did not appear to affect visual acuity or function. The persistent epithelial defect was not thought to be related to the Intacs inserts. A total of 64 subjects at month 6 (15%) and 45 subjects at month 12 (11%) had ocular complications. Intrastromal tunnel deposits were found in 213/312 (68%) patients at month 12 in the phase III trial. In this group, the magnitude ranged from trace in 36.9%, ⫹1 in 27.9%, ⫹2 in 3.2%, to ⫹3 in 0.3%. These deposits were limited to the intrastromal tunnel with no significant associated visual consequence. There were 42 reports of rating one or more of the following visual symptoms “always or severe” at month 12: difficulties with night vision (5.1%), blurry vision (2.9%), diplopia (1.6%), glare (1.3%), halos (1.3%), fluctuating distance vision (1.0%), fluctuating near vision (0.3%), and photophobia (0.3%). However, the number of subjects who were asked about symptoms (314) was lower than the number who completed 12-month follow-up for visual acuity (410), because only subjects completing questions for both the magnitude and frequency of symptoms were included. The total number of subjects who had visual symptoms is not described. No subject who reported symptoms lost more than two lines of BSCVA. The total rate of change from preoperative status of endothelial cell density to month 12 was ⫺0.4% ⫾ 4.6% for central, ⫺1.8% ⫾ 5.7% for 6:00 peripheral, and ⫺1.9% ⫾ 5.2% for 10:00 peripheral.

American Academy of Ophthalmology 䡠 Ophthalmic Technology Assessment Table 1. Results of PRK, LASIK, and Intacs Inserts for Myopia (Without Astigmatism) Premarket Data Submitted for FDA Approval Summit Excimer PRK

VISX Excimer PRK

Follow-up (months) Number of eyes Preoperative myopia range (D) Postoperative refraction ⫾ 1 D of intended correction (%) UCVA ⱖ20/40(%) 6 mo/12 mo

12 398 ⫺1.5 to ⫺7.8 95–96.7 95/99

UCVA ⱖ20/20 (%) 6 mo/12 mo

65/81

Loss BSCVA⬎2 lines (%) 6 mo/12 mo Loss BSCVA ⱖ2 lines (%) 6 mo/12 mo Increased cylinder ⬎2.0 D (%) (1 yr) Patient postop symptoms: % reporting moderate, frequent or always:

Results

blurred vision difficult night vision glare halos diplopia fluctuating vision Patient satisfaction (%): very/strongly satisfied moderately/somewhat neutral dissatisfied

Technolas LASIK

VISX LASIK

24 480 ⫺1.0 to ⫺6.5 99.6 (2 yr)

6 110 ⫺1.0 to ⫺7.0 97.8 (6 mo)

6 267 ⫺1.0 to ⫺7.0 94.9 (6 mo)

12 452 ⫺1.0 to ⫺3.0 92

100/100 (3 mo/6 mo) 86.3/85.9 (3 mo/6 mo) 0 2.1 (6 mo)

99.1 (6 mo)

96/97

68.1 (6 mo)

69/74

2.1/0 4.7/1.2

93/95/94 (6 mo/12mo/2yr) 56/64/58 (6mo/12mo/2yr) 0.4/0 (1 yr/2 yr) 1.8/0.2 (1 yr/2 yr)

0 0.8 (6 mo)

0 Data not available

0 Data not availabe

0 (6 mo)

Data not available 1.6/1.0 (6 mo/12 mo) 0

2.3 4.5 5.7 4.5 1.1 1.1 Data not available

Data not available

(6 (6 (6 (6 (6 (6

mo) mo) mo) mo) mo) mo)

86.3 11.8 2.0 0

0 (6 mo) All patients (including astigmatics) 6 (3 mo) 4 (3 mo)

2 (3 mo) Data not available

Intacs Inserts

2.9 4.8 1.3 1.3 1.6 1.3

(1 (1 (1 (1 (1 (1

yr) yr) yr) yr) yr) yr)

67 23 0 7

SOURCE: FDA PMA Files: P930034, P0930016, P990027, P990010, P980031 BSCVA ⫽ best spectacle-corrected visual acuity; D ⫽ diopter; UCVA ⫽ uncorrected visual acuity.

The adverse event rate was 1.1%, and it was defined as an event that if left untreated could be serious or have permanent sequelae. These events (n ⫽ 5) included infectious keratitis (caused by S. epidermidis), shallow placement of segment, loss of two lines of BSCVA (believed to be due to surface irregularity temporally) over two consecutive examinations, anterior chamber perforation during initial surgery, and anterior chamber perforation during exchange. In the two cases of anterior chamber perforation, it appeared that there was a deviation from the recommended standard surgical procedure. These patients recovered without significant sequelae. There were 10 phase II dissatisfaction-related removals of the Intacs inserts, and 1 phase III dissatisfaction-related removal, which could also be counted as adverse events. A total of 39 patients, or 8.7%, had the Intacs inserts explanted. Reasons included patient dissatisfaction with visual symptoms, glare, halos, night vision problems (n ⫽ 19); patient dissatisfaction with the correction achieved (n ⫽ 15); infection (n ⫽ 1); and other reasons. There were no clinically significant complications reported with explantation, and results included a return to BSCVA of 20/20 or better in all patients, clear central cornea in all eyes with remaining stromal haze and deposits within the peripheral tunnels. Some patients reported more frequent and/or more severe visual symptoms 3 months following removal of the Intacs inserts than documented preoperatively.

A total of 3.8% of patients had a secondary surgical intervention, including Intacs inserts repositioning (n ⫽ 5), punctal plug/occlusion (n ⫽ 5), a cyst/plug removal (n ⫽ 3), a filament removal (n ⫽ 2), foreign body/iron rust ring removal (n ⫽ 1), and wound revision (n ⫽ 1). Of this group, three cases were considered clinically meaningful: two patients needed a new tunnel dissected to improve the position of the Intacs inserts, and one patient had an astigmatic incision to reduce induced cylinder. Statistically significant differences were found for the safety and efficacy results of the three Intacs inserts thicknesses. The 0.35 mm thickness had poorer outcomes than the 0.25 mm and 0.30 mm thicknesses with respect to UCVA of 20/20 or better (60.6% for the 0.35 mm versus 83.7% for the 0.25 mm, and 77.5% for the 0.30 mm, P ⬍ 0.001), manifest refraction outcome within 1.00 D of predicted (85.4% versus 95.6% and 94.9% respectively, P ⫽ 0.005), induced cylinder greater than or equal to 1.0 D (11.7% versus 7.3% and 3.0%, respectively, P ⫽ 0.018) and rate of removals (13.3% versus 3.4% and 6.0%, respectively, P ⫽ 0.004). Table 1 shows a comparison of FDA premarket approval safety and effectiveness data for the original Summit (Waltham, MA) and VISX (Santa Clara, CA) excimer lasers for PRK, recent submittals for Technolas (Irvine, CA) and VISX lasers for LASIK, and the Intacs inserts. The data for the PRK and LASIK lasers reflect a broader patient contin-

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Ophthalmology Volume 108, Number 10, October 2001 uum, including patients with moderate myopia (⬎3.0 D). Reports of patient symptoms and satisfaction postoperatively were not reported uniformly across the different procedures, thus making comparison difficult. The UCVA was 20/20 or better in 64% to 86% of patients studied (during a 6-month to 2- year study period) with PRK and LASIK, compared with 74% for patients receiving Intacs inserts. The postoperative correction was ⫾1.0 D of intended correction for 94.9% to 99.6% of the patients studied (during a 6-month to 2-year study period), compared with 92% for the Intacs inserts group. From the phase III study, 165 eyes from eight clinical sites had their preoperative and postoperative videokeratographic corneal topography analyzed (at 6 months).7 Comparison of this group with postoperative corneal topography and the group of eyes (n ⫽ 245) without available postoperative corneal topography results for comparison was not described. The corneal topography analysis results demonstrated that corneal flattening occurred with placement of the Intacs inserts device, and that this flattening increased with the thickness of the device. Preoperative prolate shape of the anterior corneal surface (ranging from a corneal asphericity quotient of .50 Q to ⫺50 Q) was maintained or made more prolate after surgery. The change in topographic curvature seen was aspheric, with the median asphericity quotient of ⫺0.27 for patients with 0.25 mm Intacs inserts, ⫺0.45 for patients with a 0.30 mm Intacs inserts, and ⫺0.72 for patients with a 0.35 mm Intacs inserts. A potential benefit to maintaining prolate asphericity is that postoperative visual symptoms might be reduced because normal corneal asphericity is believed to optimize visual performance. The Multicenter European Corneal Correction Assessment Study Group assessed the refractive outcomes, complications, symptoms, and satisfaction with Intacs inserts at 12 European investigational sites from 1996 to 1997.8,9 A total of 159 eyes of 107 patients were implanted, with one of five Intacs inserts thicknesses (0.25, 0.30, 0.35, 0.40, or 0.45 mm). Patients had preoperative myopia of ⫺1.0 to ⫺6.0 D, and astigmatism ⱕ1.0 D. At 12 months, UCVA was 20/20 or better in 63% of eyes and 20/40 or better in 96% of eyes.8 At 12 months, 82% of eyes were within ⫾1.00 D of the intended correction in cycloplegic refraction spherical equivalent, and 49% were within ⫾0.50 D. Twenty-five percent of eyes had an induced cylinder ⱖ0.50 D, and 11% had ⱖ1.00 D, and 2% had ⱖ2.00 D. There were four intraoperative complications that led to withdrawal from the study: three anterior surface perforations and a posterior microperforation into the anterior chamber. There were no significant visual consequences for these patients. Also, two incisional gaps and one channel infection were found and treated. Eight percent of Intacs inserts were removed because of dissatisfaction with vision (undercorrection and induced astigmatism, n ⫽ 8), visual symptoms (n ⫽ 2), persistent incision gape (n ⫽ 1), and stromal thinning due to a shallow pocket (n ⫽ 1).9 After removal, one eye lost more than two lines of BSCVA and was 20/50. Postoperatively, 68% of patients reported mild to moderate pain and discomfort, such as a foreign body sensation

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and photophobia.9 At 12 months, 9% of eyes were noted to have mild photophobia and 1% had moderate photophobia. The following symptoms were noted at 12 months: fluctuating distance vision (25% for mild, 8% for moderate), double vision (13% for mild, 6% for moderate), glare (9% for mild, 2% for moderate), and halos (5% for mild and moderate). Patient satisfaction was reported as excellent for 47% of patients, good for 41%, fair for 9%, and poor for 2%. One study conducted in France evaluated the effect of Intacs inserts shift on outcome.10 In this group of 47 eyes with myopia from ⫺1.0 to ⫺5.0 D, migration and contact between the two segments occurred in 45% of the eyes. In two eyes, the superior ends were in contact, which was associated with wound-healing problems, superficial channels, and eventual Intacs inserts explantation. There were no significant differences in terms of visual acuity (ranging from 20/20 –20/40), density of intrastromal deposits, or reporting of halos and glare between the group with contact between the implant segments and the group without contact. However, at 6 months there was more induced cylinder in the group with segment contact (mean ⫹1.3 ⫾ 0.7D versus 0.7D ⫾ 0.5 D). A study of 10 eyes with Intacs inserts placement showed an evening myopic shift at 1 year.11 The same tests, including refraction and keratometry, were also performed on 22 normal eyes without surgery and 10 eyes that had excimer laser PRK at the same time. A diurnal variation of greater than 0.50 D occurred in 20% of eyes with Intacs inserts procedures, 20% of eyes with PRK procedures, and 22.8% of normal eyes. Keratometric variations of more than 0.10 mm at least one time per day occurred in 40% of the Intacs inserts group but not in the PRK and control eyes. Another study evaluated the diurnal changes in visual acuity and refraction in eyes implanted with the Intacs inserts.12 This study involved two different groups of patients, including 52 patients with bilateral Intacs inserts and 15 patients with unilateral Intacs inserts. There was no clinically significant variation in visual acuity or refraction found after Intacs inserts placement in either group. Ninetyfive percent of the bilateral treatment group was within one line of BSCVA. One study evaluated predicted corneal acuity before and after Intacs inserts placement using a clinical videokeratoscope.13 Predicted corneal acuity is a topographic index that is intended to estimate the potential optical quality of the central anterior surface of the cornea. Surfaces with irregularities have a lower predicted corneal acuity than do surfaces without irregularities, indicating a potential difference in optical performance. Ninety-four eyes from the phase II trials with ⫺1.00 to ⫺6.00 D of myopia were studied preoperatively and at 3 months postoperatively. Preoperatively, 98% of eyes had a predicted corneal acuity of 20/10. At 3 months, 98% of moderately myopic eyes maintained a predicted corneal acuity of 20/10. This suggests that the Intacs inserts placement did not result in central corneal surface irregularities that would lead to decreased optical performance, as measured by videokeratography. Flying-slit confocal microscopy was performed on 21

American Academy of Ophthalmology 䡠 Ophthalmic Technology Assessment eyes of 11 patients after Intacs inserts placement.14 The average time after placement was 8.6 months. The evaluations found normal morphology of the central corneal zone, but they also found evidence of wound healing adjacent to the Intacs inserts, with moderate fibrosis. One study evaluated refractive effect after removal of the Intacs inserts.15 Out of 34 explantations from the FDA phase II and III trials, 21 were evaluated at 3 months (62% follow-up). Twenty-one eyes were within ⫾ 1 line of preoperative BSCVA (100%) and 16 eyes returned to within ⫾ 1 line of preoperative UCVA (76%). Eighteen eyes (86%) were within ⫾0.50 D of preoperative manifest spherical equivalent refraction. There do not appear to be significant safety issues as a result of Intacs inserts removal. Also, a follow-up study of surgically induced astigmatism after Intacs inserts placement showed that mean induced astigmatism was 0.13 D ⫾ 0.52 D.16 The Intacs inserts have also been used in patients with keratoconus.17 In a small case series of 10 patients, the Intacs inserts appeared to reduce astigmatism and spherical correction. Topographical regularity was increased and UCVA increased. One retrospective analysis was performed to compare eyes with Intacs inserts (n ⫽ 82) with eyes treated with LASIK (n ⫽ 133).18 Patients from both groups had preop-

erative myopia of ⫺1.00 to ⫺3.50 D, astigmatism of ⱕ1.00 D, and single treatment. At one day UCVA was 20/20 or better in 24% of eyes after Intacs inserts and in 55% of eyes after LASIK. At 3 months UCVA was 20/20 or better in 75% of eyes after Intacs inserts and in 67% of eyes after LASIK.

Conclusions To date, evidence suggests that low myopia (⫺1 to ⫺3D) in a well-defined group of patients who have a stable manifest refraction and less than ⫹1.0 D of astigmatism can be treated with Intacs inserts with a reasonable assurance of safety and effectiveness. The FDA approved this procedure for a limited range of myopia, and there are other available alternative procedures for low myopia. Nearly 9% of patients requested to have their inserts removed and 4% of patients required a secondary surgical procedure. During the 12-month reporting period, 11% of subjects experienced ocular complications but were treated successfully. One case remained under treatment at month 12. Additional clinical research is needed to determine the long-term effectiveness of treatment and the comparative safety, effec-

Preparation was coordinated by the Ophthalmic Technology Assessment Committee Refractive Surgery Panel Refractive Surgery Panel 2000–2001

Christopher J. Rapuano, MD, Chair Peter J. Agapitos, MD William W. Culbertson, MD Vincent P. de Luise, MD David Huang, MD, PhD Douglas D. Koch, MD Gary A. Varley, MD Alan Sugar, MD, MS Susan Garratt Flora Lum, MD Nancy Collins, RN, MPH Margo Leslie Board of Trustees, June 10, 2001

Edited by: Managing Editors

Approved by:

*Proprietary Interests N N N N N N N C3 N N N N

*Proprietary interests stated Category

Abbrev

Specific Financial Interests

Product Investor

P Pc I

Consultant

Ic C

Financial interest in equipment, process, or product presented. Such interest in potentially competing equipment, process, or product. Financial interest in a company or companies supplying the equipment, process, or product presented. Such interest in a potentially competing company. Compensation received within the past three years for consulting services regarding the equipment, process, or product presented. Such compensation received for consulting services regarding potentially competing equipment, process, or product. Examples of compensation received include: 1. Retainer 2. Contract payments for research performed 3. Ad hoc consulting fees 4. Substantial non-monetary perquisites 5. Contribution to research or research funds 6. Contribution to travel funds 7. Reimbursement of travel expenses for presentation at meetings or courses 8. Reimbursement of travel expenses for periods of direct consultation No financial interest. May be stated when such interests might falsely be suspected.

Cc

None

C1 C2 C3 C4 C5 C6 C7 C8 N

or or or or or or or or

Cc1 Cc2 Cc3 Cc4 Cc5 Cc6 Cc7 Cc8

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Ophthalmology Volume 108, Number 10, October 2001 tiveness, and costs with other treatment modalities, including LASIK and PRK. Patient safety should be of highest consideration, given that candidates for refractive surgery are healthy and have correctable vision. In selecting the appropriate refractive surgical procedure for an individual patient, the ophthalmologist has many factors to consider: patient preference, expectations, life-style, visual needs, and preexistent ocular conditions. In addition, the relative costs, risks, and benefits among the different procedures must be considered. For example, the Intacs inserts are removable and maintain the prolate shape of the cornea; however, this device is limited to a group of patients with low myopia without astigmatism and long-term outcomes are not defined. Ophthalmologists have considerably more experience with LASIK and PRK, which can be used for a broader group of patients with low, moderate, and high myopia with or without astigmatism, but these procedures are also associated with problems of stromal ablation and corneal haze. While the clinical safety and efficacy data of Intacs inserts appear comparable to PRK and LASIK, the technology has not been embraced by refractive surgeons and patients. The likely reasons are that the refractive indications are more limited (low degree of essentially spherical myopia), it is a new skill to learn and very different from PRK, LASIK, and cataract surgery, and it is expensive for the surgeon to undertake but generally costs the same as LASIK for the patient.

Future Research The following questions about intrastromal corneal ring segments need to be addressed in future research. ●

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What are visual function outcomes after Intacs inserts placement, including visual acuity as well as contrast sensitivity, subjective measures, quality of life assessments, and other qualitative measures of vision? What are its relative risks, costs, and benefits compared to available treatments and new treatments under investigation, e.g., LASIK and PRK? Is there any risk of long-term endothelial cell loss (beyond 2 years)? What risk factors are associated with poorer clinical outcomes or complications, and what can be done to ameliorate them? What is the performance of Intacs inserts in routine clinical practice? What future developments in technology can be anticipated or are needed for improvement? Can it be modified to treat astigmatism? Hyperopia? What is its role in treatment of patients with mild keratoconus?2

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References 1. Burris TE. Intrastromal corneal ring technology: results and indications. Curr Opin Ophthalmol 1998;9:9 –14. 2. Schanzlin DJ. Studies of intrastromal corneal ring segments for the correction of low to moderate myopic refractive errors. Trans Am Ophthalmol Soc 1999;97:815–90. 3. Twa MD, Karpecki PM, King BJ, et al. One-year results from the Phase III investigation of the KeraVision Intacs. J Am Optom Assoc 1999;70:515–24. 4. Schanzlin DJ, Asbell PA, Burris TE, Durrie DS. The intrastromal corneal ring segments. Phase II results for the correction of myopia. Ophthalmology 1997;104:1067–78. 5. Nose W, Neves RA, Burris TE, et al. Intrastromal corneal ring: 12-month sighted myopic eyes. J Refract Surg 1996;12: 20 – 8. 6. KeraVision Intacs. Part 2. Summary of Safety and Effectiveness Data. April 30, 1999. P980031, U.S. Food and Drug Administration. 7. Holmes-Higgin DK, Burris TE. Corneal surface topography and associated visual performance with Intacs for myopia: phase III clinical trial results. The Intacs Study Group. Ophthalmology 2000;107:2061–71. 8. Ruckhofer J, Stoiber J, Alzner E, et al. One year results of European multicenter study of intrastromal corneal ring segments. Part 1: refractive outcomes. J Cataract Refract Surg 2001;27:277– 86. 9. Ruckhofer J, Stoiber J, Alzner E, et al. One year results of European multicenter study of intrastromal corneal ring segments. Part 2: complications, visual symptoms and patient satisfaction. J Cataract Refract Surg 2001;27:287–96. 10. Cochener B, Savary-LeFloch G, Colin J. Effect of intrastromal corneal ring segment shift on clinical outcome: one year results for low myopia. J Cataract Refract Surg 2000;26:978 – 86. 11. Baikoff G, Maia N, Poulhalec, et al. Diurnal variations in keratometry and refraction with intracorneal ring segments. J Cataract Refract Surg 1999;25:1056 – 61. 12. Twa MD, Hurst TJ, Walker JG, et al. Diurnal stability of refraction after implantation with intracorneal ring segments. J Cataract Refract Surg 2000;26:516 –23. 13. Holmes-Higgin DK, Burris TE, Asbell PA, et al. Topographic predicted corneal acuity with intrastromal corneal ring segments. J Refract Surg 1999;15:324 –30. 14. Ruckhofer J, Bo¨hnke M, Alzner E, Grabner G. Confocal microscopy after implantation of intrastromal corneal ring segments. Ophthalmology 2000;107:2144 –51. 15. Asbell PA, Ucakhan OO, Abbott RL, et al. Intrastromal corneal ring segments: reversibility of refractive effect. J Refract Surg 2001;17:25–31. 16. Twa MD, Ruckhofer J, Shanzlin [sic.] DJ. Surgically induced astigmatism after implantation of Intacs intrastromal corneal ring segments. J Cataract Refract Surg 2001;27:411–5. 17. Colin J, Cochener B, Savary G, Malet F. Correcting keratoconus with intracorneal rings. J Cataract Refract Surg 2000; 26:1117–22. 18. Suiter BG, Twa MD, Ruckhofer J, Schanzlin DJ. A comparison of visual acuity, predictability, and visual function outcomes after intracorneal ring segments and laser in situ keratomileusis. Trans Am Ophthalmol Soc 2000;98:51–5; discussion 55–7.