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Automated Lamellar Keratoplasty
Preliminary Procedure Assessment*
Automated Lamellar Keratoplasty American Academy of Ophthalmology * The purpose of the Committee on Ophthalmic Procedures Assessments is to eval uate on a scientific basis new and existing ophthalmic tests, devices, and procedures for their safety, efficacy, clinical effectiveness and appropriate uses. Evaluations include examination of available literature, epidemiological analyses when appropriate, and compilation of opinions from recognized experts and other interested parties. After appropriate review by all contributors, including legal counsel, assessments are submitted to the Academy's Board of Trustees for consideration as official Academy policy.
Introduction to Preliminary Procedure Assessments The rapid integration of successful new technology into ophthalmic practice is a complex process. Industry must market the emerging technology fairly and accurately. It is the responsibility of innovators and early adaptors to plan well-designed studies and present prompt, accurate, and comprehensive results in peer-review journals. The limitations and benefits of the new technology can be evaluated fairly only when these studies are well executed and reported in a timely fashion. Judgments are less likely to be correct when study design is poorly conceived, mar keting claims are inaccurate, and peer-review information is delayed or nonexistent. Recent methodologic reviews of the literature of cat aract extraction 1•2 and the review of keratomileusis and keratophakia by the American Academy of Ophthalmol ogy showed apparent deficiencies in the rigor of research methods used to evaluate the safety and efficacy of in novative ophthalmic technology. These studies concluded that ophthalmologists should improve the rigor ofresearch in ophthalmic surgery. That improvement will require more careful attention to fundamental principles ofstudy design, data analysis, and reporting. In response, the Academy has designed the Prelim inary Procedure Assessment (PPA) to complement the Prepared by the Committee on Ophthalmic Procedures Assessment and approved by the American Academy ofOphthalmology's Board ofTrus tees, November 1995.
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standard Ophthalmic Procedures Assessment that it has provided its members since 1982. 3 The preliminary assessments begin the evaluations earlier to help define the questions to be answered before more formal methodologic reviews take place. These assessments also provide feedback to industry and clinicians in vestigating new technology so that they can improve the quality of their data collection and presentation before the standard assessment proceeds. The goals of the preliminary assessment are to improve the effi ciency of innovation of new products and procedures, and to aid all parties interested in an objective eval uation of these new technologies. To accomplish these goals, the preliminary assessments in general are intended to do the following: • Describe the theoretical or scientific basis for opti mism about the emerging technology. • Summarize and complement the information that industry presents on emerging and innovative ophthalmic procedures. • Test the accuracy of marketing claims and identify questions that require careful and detailed scientific investigation before the procedure should be consid ered safe and effective. • Critically review the current literature in the field. • Describe clinical trials in progress and present antic ipated dates of study completion. The American Academy ofOphthalmology emphasizes that the preliminary assessment document is only one of the expected outcomes of the assessment process. Another
American Academy of Ophthalmology · Automated Lamellar Keratoplasty outcome is the establishment of more rigorous research methods. This pilot assessment on automated lamellar keratoplasty (ALK) generated debate among a wide range of experts, from creative innovators to methodologists. As consensus based on current scientific literature strengthened, most innovators saw the need to improve the quality of their science and suggested that methodol ogists, scientists, and innovators work together to generate more rigorous protocols to answer questions of interest to the patient. Reviewers also saw the need to analyze new articles on ALK very soon after publication so that this document does not become obsolete instantly. It is anticipated that these suggestions will soon tum into real ity so that the Academy membership and the public re ceive the credible analysis of new technology they desire.
The Automated Lamellar Keratoplasty Preliminary Procedure Assessment The Academy selected ALK as the topic for the first PPA for a number of reasons. The technology has promise in the correction of high myopia and perhaps also hyperopia. Lamellar technology is evolving from earlier microkera tome systems that were associated with clinically signifi cant complications. 3 Significant challenges remain in finding safe and efficacious methods for the surgical cor rection of high myopia and hyperopia. A large number of alternative procedures have been proposed and are under investigation, including clear lens extraction, phakic intraocular lenses, excimer laser pho torefractive keratectomy, laser in situ keratomileusis, and automated lamellar keratoplasty. The peer-review litera ture contains a paucity of information on the relative safety and efficacy of these competing approaches. The literature does demonstrate that patients with severe re fractive errors are often highly motivated to correct their problem surgically. Many patients will consider the sur gery a success, even if severe degradation of night vision and other problems related to optical quality develop. 4 There is reason to suspect that automation in the new technology may not completely eliminate some of the complications, and there is reason to suspect that problems will occur with optical quality that are independent of refractive accuracy, especially night aberration. 4 •5 Automated lamellar procedures have been heavily marketed in nonpeer-review literature, but peer-review articles on clinical results were almost nonexistent as of October 1995. 5•6 Because the older microkeratomes pre dated the Federal Drug Administration (FDA) regulatory approval process, current microkeratome systems are said to be equivalent and are "grandfathered" in without re view. The ophthalmic community will be better able to evaluate this technology if the leaders in innovation pres ent data in a framework that convinces others that the technology has a clinically acceptable level of safety and efficacy. This document will not analyze laser in situ keratom ileusis. That surgical technique will be the subject of a later PPA.
Historical Background Automated lamellar keratoplasty represents the newest in a series of surgical techniques in keratorefractive surgery to evolve from the work of Castroviejo and Barraquer, 3 who performed the earliest studies with the microkera tome-the instrument that is common to all these tech niques. These early researchers designed and later updated this instrument to remove a disc of the anterior corneal stroma so that they could lathe it, resuture it to the corneal surface, and thereby alter refractive error. Throughout the late 1980s, the primary procedures under investigation were keratomileusis and keratophakia. The Academy's 1992 Ophthalmic Procedures Assess ment entitled Keratomileusis and Keratophakia: Safety and Effectiveness, describes the peer-review literature ex tant through the late 1980s. 3 It concluded that these pro cedures had a small, well-defined role in the surgical man agement of high refractive errors, whether myopic or hy peropic. Although a large number of surgeries were performed, few well-controlled studies existed. Reported complication rates were significant and serious in some studies. Even skilled surgeons had visually significant complications in 1% to 14% of patients. The major prob lems included the complexity of the procedure and equipment, the delayed visual rehabilitation, the potential for mild to severe loss of Snellen visual acuity, decrease in quality of vision from glare, Joss of contrast sensitivity, inaccuracy of refractive results, and postoperative com plications involving principally re-epithelialization and wound healing. The 1992 assessment also concluded that well-designed prospective studies were needed to evaluate these techniques objectively so that they could be com pared with surgical alternatives for the correction of high myopia and high hyperopia.
Scientific Basis for Renewed Optimism for Microkeratome-based Systems Changes in Microkeratome Design A perfect microkeratome system would give predictable lamellar sections. The sections would invariably be well centered. The lenticule would be of appropriate thickness and diameter. The interface would show a smoothly cut surface rather than periodic nonuniform incisions caused by vibration-induced chatter ofthe microkeratome blade. The micro keratome blades would be of high quality and show flawlessly honed blade surfaces without fracture lines, debris, or score lines. The nonautomated microkeratome did not consistently meet these criteria. The depth of cut was variable. Ex perienced surgeons inadvertently entered the anterior chamber in 1% to 2% of patients, despite a predicted in cision depth of 130 to 160 ~-tm. Clinical studies note discs with diameters that were smaller than the predicted size to such a degree that they Jed to clinically significant re duction of visual acuity in 2% to 3% of patients. 3 Risto
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logic findings also showed characteristic nonsmooth in terfaces (chatter) caused by blade vibration. 7 Fast passage of the microkeratome over the surface gave superficial cuts; slow passage gave deeper cuts. There is renewed interest in keratomileusis as ophthal mologists search for an effective means to correct higher amounts of myopia (> -6.0 diopters). Excimer laser trials on this higher myopia group show poorer predictability, more postoperative scarring, greater refractive regression, and more severe visual aberrations when compared with results of similar trials for lower amounts of myopia (<6.0 diopters). 8 While excimer trials progressed, micro kera tome manufacturers improved the quality of the micro keratome systems. Some manufacturers have automated their systems to allow the keratome to pass over the cor neal surface without the surgeon controlling it, because they believed the manual pass caused many of the prob lems with the earlier systems. 9 •10 The quality of micro keratome blades also is improved. The new automated microkeratomes are designed to approximate more closely the criteria of an ideal microkeratome.
Changes in Microkeratome-based Procedures Keratomileusis In Situ for Myopia. This procedure flat tens the central cornea by excising and discarding a vol ume of stroma located between the superficial and deep stromal lamellae. The excised area is centered over the pupil and is 3.5 to 5.0 mm in diameter. The thickness and diameter of the excised stromal lenticule determine the amount of myopia corrected. Early investigators ex posed the surgical field for the lenticule resection by tem porarily displacing from the central cornea a free disc of anterior stroma 160 ~m thick and 7.2 mm in diameter (Ruiz and Rowsey; presented as an abstract at the ARVO Annual Meeting, Sarasota, 1988). After discarding the deeper stromal lenticule, the anterior stromal disc con formed to the base of the excision site and the disc's an terior surface flattened as well. The anterior stromal free disc has now been replaced with an anterior stromal flap. The flap has the same di ameter as the disc used in earlier procedures. It differs from a disc in that it remains attached to bordering an terior stroma for approximately 30° of its circumference. Some researchers are investigating whether flap thickness should be reduced to 130 ~m rather than the 160-~m thickness used in earlier studies. Keratomileusis In Situ for Hyperopia. Ruiz observed steepening of the anterior corneal curvature when the stromal thickness of a micro keratome pass exceeded 60% of the central corneal thickness (written communication; Charles Casebeer, MD, January 1995). The unresected stroma deep to the resection bulged forward as a result of the overlying resection. When the flap was re-approxi mated to the ectatic deeper stroma, it conformed to ectasia induced by the resection. The anterior curvature of the flap steepened as a result. The amount of steepening is controlled by the diameter of the cut. Progressive myopic shift may result.
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Automated Lamellar Keratoplasty. Automated la mellar keratoplasty is the name given to the in situ ker atomileusis procedure performed with the newly designed automated microkeratomes.
Marketing Marketing Claims and Their Implications Promotional material from Chiron Vision (Irvine, CA), the main microkeratome marketer, promises standardized quality: ". . . precise corneal discs of preselected thickness and diameter . . ." and a ". . . dramatic increase in the accuracy of the cut." These promotional handouts indi cate that the microkeratomes allow the user to ". . . cut a precise corneal disc of preselected thickness and di ameter-accurately." The handouts state, "The keratec tomy is now performed with the same exact movement every time, with every surgeon." ' The Summer 1995 issue ofthe Casebeer System Update states, "Automated Lamellar Keratoplasty is proving to be an extremely valuable procedure. We have made many improvements to the procedure resulting in better pre dictability and safety. It is now apparent, for a variety of reasons, that ALK is an essential part of the armamen tarium of a surgeon who chooses to be a comprehensive keratorefractive surgeon." Figure 1, which was first gen erated in 1993, shows that the Casebeer system suggests ALK as one of two alternatives to correct 1 to 6 diopters of hyperopia and 5 to 35 diopters of myopia. If the marketing claims are correct and the microker atomes do give consistent, accurate results every time, then the technology is more likely to obtain reproducible results. Any initial errors in refractive accuracy should require simple adjustments in the nomograms. If the claims are not correct, however, results with any micro keratome-based procedures will be heterogeneous, equip ment failures will occur that could threaten vision 3•5 no mograms will not be easy to adjust, and a greater 'risk of inaccurate corrections and degraded optical performance will be incurred. 4 •5
Evaluating the Accuracy of Marketing Claims To test the accuracy of marketing claims about the im proved accuracy and predictability ofcuts from automated microkeratomes, answers to the following questions are necessary: • How is each component ofthe lamellar disc (interface smoothness, accuracy, and reproducibility of disc diameter; accuracy and reproducibility ofdisc thick ness) affected by automating the pass ofthe micro keratome? • Do microkeratomes produce primary (superficial flap) and secondary (refractive power lenticule) cuts of equal reproducibility and quality? • How often can one expect equipment-related failure with the newer technology? What are the clinical consequences of mechanical failure?
American Academy of Ophthalmology
Automated Lamellar Keratoplasty
+6 +5 +4 +3 +2 +1 0 -1 -2 -3 -4 -5 -6 -7 -8 -9 -10 -11 -12 -13 -14 -15 -16 -17 -18 -19 -20 -21 -22 ...... -30
Astigmatism +6 +5 +4 +3 +2 +1 0
Figure 1. Marketing nomogram from the Casebeer Comprehensive Refractive Surgeon Nomogram. (Reprinted from Casebeer JC, Slade S: The Comprehensive Approach to Keratorefractive Surgery. Unpublished course material. Scottsdale, AZ; 1993.) AK = astigmatic keratotomy; LASIK = laser in situ keratomileusis; RK = radial keratotomy; ALK = automated lamellar keratoplasty; PRK = photorefractive keratectomy.
• What is the learning curve for microkeratome-based systems? • Does literature exist to allow one to compare the quality of the primary and secondary resections of competing automated microkeratomes? What should be the minimal acceptable measurement criteria for such a study?
•
To test the accuracy of marketing claims about clinical results with automated microkeratomes, answers to the following questions are necessary:
•
• What studies prove that ALK gives superior results in optical quality, refractive accuracy, and rates of serious complications when compared with manual pass keratomileusis in situ? • What are the most common complications observed (and reported rates of occurrence) with automated microkeratome systems? • Do vision-threatening complications occur with au tomated microkeratome systems? • Does ALK cause a higher rate of degraded optical quality and refractive instability in patients with pre vious refractive surgery? • Can permanent central artery occlusion occur as a result of the high intraocular pressure generated by the microkeratome's suction device? • What are the inherent problems likely to remain with microkeratome-based systems, regardless of the
•
• • • • •
quality and reproducibility ofthe microkeratome in cisions? How does the optical quality of ALK surfaces (e.g., size of uniform optical zone, centration, ir regular astigmatism) compare with optical quality after radial keratotomy, excimer laser photore fractive keratectomy, and laser in situ keratomi Jeusis? How do results compare with photorefractive kera tectomy in the same refractive range? With radial keratotomy in the same refractive range? Do refractive results stabilize in all cases of ALK for myopia and ALK for hyperopia? Does ALK cause a higher rate of degraded optical quality and refrac tive instability in patients with previous radial ker atotomy than it does in patients without previous refractive surgery? What are the rate and variability of visual recovery? Is there a difference in visual acuity, refractive results, astigmatism, and complications ofthe free-cap versus hinged-cap techniques? What is the refractive accuracy of ALK before en hancement surgery? How frequently are patients left with clinically sig nificant distortion of central vision"r-6 How frequently are patients left with clinically sig nificant aberration of peripheral vision? Of night vi sion"r-6
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• What percentage of patients with subjective com plaints of severe night vision disturbance, glare, or halos are nevertheless happy with the overall result of ALK? • Are results stable over the long term? Is long-term stability affected by incisional enhancement surgery? • Is there a greater risk of postoperative complica tions in patients with previous radial keratotomy than in patients with no previous refractive sur gery? How often will ocular trauma lead to dis placement of the ALK flap or cap? What are the visual sequelae of these displacements? How often will ocular trauma lead to globe perforation in pa tients requiring radial keratotomy or relaxing in cision after ALK?
Review of Nascent Literature Studies Comparing the Accuracy and Reproducibility of Discs, Flaps, and Stromal Lenticules Obtained by Automated and Nonautomated Keratomes during Keratomileusis In Situ Clinical Studies. No published peer-review studies were found in the literature review on this subject as of October 1995. Eye Bank Studies. In the absence of clinical studies, eye bank studies offer the best, albeit imperfect, answers to some of the questions raised above. Eye bank eyes are not dynamic. There may be differences in lamellar integ rity. Intraocular pressure may be difficult to control. Eye bank studies do not have to deal with the suction problems of narrow intraorbital fissures and redundant conjunctiva that occur in a subset of patients. The eye bank study performed by Hofmann and Bechara9 compared two automated microkeratomes with a second-generation microkeratome that bad a manual drive. The component parts are shown in Table 1. Each system performed five keratomileusis in situ primary ker atectomies, five secondary 100-.um keratectomies, and one deep (400-.um) lamellar keratectomy. The study evaluated the surface characteristics of the keratectomy sites as well as the accuracy of the diameter and thickness of the la mellar keratectomies. The reviewing methodologist gave
the study an intermediate rank for scientific quality be cause the information was acquired from cadaver eyes. Hofmann and Bechara9 found that both the automated microkeratomes and the manual keratome produce cuts of nonuniform thickness (chatter). The hand-advanced system showed an irregular pattern of chatter, whereas the chatter lines in the two automated systems were ar ranged parallel to the edge of the blade and had a regular pattern. Reproducibility of Disc Thickness and Diameter during Primary Keratectomy. Hofmann and Bechara9 observed that the mean section diameters were 10% to 20% smaller than the predicted diameter of 7.2 mm for all three microkeratomes. The Steinway instrument (Chi ron Vision) tended to generate stromal discs thicker than predicted, whereas the other instruments tended to gen erate discs thinner than predicted. All three microkera tomes showed a range of deviation from predicted thick ness of more than 20 ,urn. Reproducibility of Disc Thickness and Diameter during Secondary Keratectomy. Hofmann and Bech ara9 noted that the diameters ofthe secondary keratectomy showed a variation from the predicted diameter of 6% for the Steinway automated microkeratome, 9% for the Draeger Lamellar Keratome (Storz Instrument GmbH, Heidelberg, Germany), and 25% for the manual keratome. Hofmann and Bechara9 observed the variability in the thickness of the lenticule resections. The Steinway auto mated microkeratome tended to cut thicker sections than predicted, and the other systems tended to cut thinner sections than predicted. The range of deviation from pre dicted thickness was 22 .urn for the Stein way instrument, 24 .urn for the manual microkeratome, and 7.8 .urn for the Draeger instrument.
Peer-review Literature on Keratomileusis In Situ and Automated Lamellar Keratoplasty Keratomileusis In Situ. Two peer-review articles on keratomileusis in situ using nonautomated microkera tomes were identified 11 • 12 (see Table 2). Both reports were published in 1991 on surgery performed in the late 1980s with older microkeratome designs. The methodologist re viewing these artilces gave each study a low rating for scientific content. The low rating was based on three fac tors: ( 1) the results were not reported at a defined post-
Table 1. Comparison of Component Parts of Microkeratomes Tested by Hofmann and Bechara9 Model Name Component Parts Motor Blade movement Adjustable suction ring Change of depth plate Movement across cornea
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Steinway (automated corneal shaper)
Draeger (automated lamellar keratome)
Microprecision Test Model
Electric Oscillating Yes Interchangeable plates Mechanical: gear driven
Electric Rotary
Gas turbine Oscillating
No Interchangeable plates Mechanical: screw driven
No Adjustable screw Manual
American Academy of Ophthalmology · Automated Lamellar Keratoplasty Table 2. Results of Keratomileusis In Situ with Nonautomated Microkeratomes Peer-review Article #l Bas and Nano, 1991 Prospective No 30/17 Myopia, > -8.00 D Astigmatism, < 5.00 D Age,> 20 yrs Keratometry, 40-47 D Central corneal thickness, 0.50-0.70 mm Steinway Barraquer IBM-PC Diameter, 6.5-8.0 mm Thickness, 0.10-0.18 mm Diameter, 3.25-5.00 mm Thickness, 0.08-0.20 mm 11
Type of study Institutional review board approved No. of eyes/patients Entry criteria
Microkeratome Nomogram First-pass parameters Stromal resection Cap fixation
Antitorque suture
Intraoperative Complications First pass Inaccurate thickness Disc rupture Decentration Inaccurate diameter
NA 1/30 3/30 NA
Jammed keratome Stromal resection Inaccurate thickness
Arenas-Archila et a!, 1991 12 Prospective No 32/17 Myopia,> -4.5 D Astigmatism, NA Age,> 19 yrs Keratometry, > 39.25 D Corneal thickness, > 0.52 mm Barraquer Ruiz Diameter, 7.2 mm Thickness, 0.180-0.200 mm Diameter, 4.2 mm Thickness, 0.05-0.20 mm, depending on intended correction Antitorque suture
In slightly less than· 50% 1/32 NA "Routinely" close to calculated 7.2-mm diameter, but no documentation 1/32
NA 3/30 (required second resections)
28/32 inaccurate 9 require second stromal resection 2 require total stromal resection "Irregular oval shape in almost every case" 1/32 decentered resection with edge bisecting pupil
Inaccurate diameter Decentration
NA NA
Jammed keratome
NA
0/32
NA 3/30 4/30 7/30 7/30 monocular diplopia at night 1 allograft disc for disc rupture 4 radial keratotomies for undercorrection 1 removal of large epithelial implantation 10/30 required 6 mos to achieve best vision Cannot evaluate; many amblyopic preoperatively 6/30 amount and time course of regression not documented
1/32 when cap placed epithelial side down 2/32 3/32 NA NA 1 reposition of epithelial side down graft 1 repeat myopic keratomileusis in situ 55 days after healing of ruptured disc NA
Postoperative Complications Severe interface opacity Minor interface opacity Epithelial implantation "Irregular astigmatism" Night aberration Secondary procedures Delayed visual recovery Two or more lines loss of vision Late refractive regression Refractive Accuracy Time of report Manifest within 1 D Manifest within 2 D Manifest > 5 D from emmetropia Type of refraction D
Peer-review Article #2
=
diopter; NA
=
360-540 days after surgery 8/30 19/30 6/30 Manifest
8/32 NA 90-194 days after surgery 3/16 from -10- to -21-D group 8/16 from -10- to -21-D group 6/15 from -5.25- to -9.75-D group 10/16 from -10- to -21-D group 10/16 from -5.25- to -9.75-D group Cycloplegic
not available.
operative time; (2) both eyes were included from single patients, which interfered with the randomness of the study; and (3) the studies reported on mean visual acuity instead of on the fraction of patients achieving a defined level of visual acuity.
A review of Table 2 shows significant problems with microkeratome resections, especially the stromal resec tions. These results corroborate the eye bank data, which show a less reproducible second microkeratome pass (lenticule excision). Refractive accuracy is less than
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Ophthalmology Table
3. Summary of Complications Associated with Automated Microkeratomes
Decentered ablations Cap melts Holes in caps Nonadherent caps Recurrent corneal erosion Infection Ectasia associated with refractive regression Loss of two or more lines of visual acuity Interface scarring Large overcorrection Large undercorrection Noncircular secondary lamellar resections
adequate (range, 20%-63%; >5 diopters from emme tropia postoperatively). Complications are high enough for the authors of one of the articles to conclude that " . . . in our hands, myopic keratomileusis in situ was not a technically safe, precise and predictable technique for the correction of myopia. Further improvements in the technique and equipment may provide better re sults." 12 Automated Lamellar Keratoplasty for Myopia. No articles on this procedure were identified in the peer-review literature as of October 1995. Studies submitted for pub lication and in progress are described in the following section on clinical trials in progress. It remains unclear how well the studies will answer the questions posed until results are published and undergo content and method ologic review. Abstracts on ALK were presented at the International Society of Refractive Surgery (formerly In
Table Case No. 1 2 3
4
5
6 7 8 9 10 11 12
Indication for ALK Myopia Myopia Hyperopia Myopia Myopia Myopia Myopia Hyperopia Myopia Myopia Myopia Myopia
4.
Months Cap in Place <1 17 16 7
3 2 3 4 <1 6
ternational Society of Refractive Keratoplasty) Meeting in San Francisco in October 1994. Table 3 shows the list of complications associated with the automated systems based on a review of all abstracts on keratome-based pro cedures. Schneider and colleagues evaluated 66 eyes 6 months after ALK for myopia (presented as an abstract at the ARVO Annual Meeting, Ft. Lauderdale, 1995). Fifty-four percent of patients showed uncorrected visual acuity of 20/40 or better, but 22% of patients lost two or more lines of best-corrected visual acuity. The number of patients who required secondary procedures to obtain 20/40 visual acuity without correction were not identified, nor was night vision disability discussed. Mamalis and colleagues report in an extended abstract on 12 corneal caps removed from 12 patients after ALK (see Table 4) (American Society of Cataract and Refractive Surgery Symposium of Cataract, IOL, and Refractive Sur gery, Boston, 1994). The caps were obtained over a 6-month period. All patients had surgery using the cap rather than flap technique. Seven ofthe removed caps were from patients with refractive procedures before the ALK procedure. The authors of the abstract could not document the incidence of cap complications because the caps were received from an undisclosed number of surgeons performing an undis closed number of procedures. Final visual outcome is not discussed, because this abstract dealt with the histopathologic findings of failed or removed caps. Automated Lamellar Keratoplasty for Hypero• pia. The peer-review literature contains no articles on ALK for hyperopia. Studies submitted for publication and currently under way are described in the following section. It remains unclear how well the studies will answer the questions posed until results are published. According to instructors of the January 1995 Chiron Vision course on ALK for hyperopia, progressive ectasia,
Patient Characteristics* Complication
Cap Disposition
Dislocated cap Irregular astigmatism Irregular astigmatism Irregular astigmatism Irregular astigmatism Irregular astigmatism Epithelial ingrowth Suspected infection Irregular astigmatism Fragmented cap Haze Dislocated cap
Fell off Removed Removed Removed Removed Removed Removed Removed Removed Fell off Removed Fell off
Other Prior Surgical Procedure PKP RK, cap sutured RK RK RK Cap sutured RK Excimer RK
• Source: Mamalis N, Lucius R W, Casebeer C. Histopathologic analysis of cornea caps removed after automated lamellar keratoplasty. American Society of Cataract and Refractive Surgery Symposium of Cataract, IOL, and Refractive Surgery; Boston; 1994. ALK = automated lamellar keratoplasty; PKP = penetrating keratoplasty; RK = radial keratotomy.
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American Academy of Ophthalmology · Automated Lamellar Keratoplasty myopia, and irregular astigmatism have been observed among a subgroup of patients when the stromal thickness of the microkeratome pass exceeds 80%. Ruiz has per formed more than 200 penetrating keratoplasties to cor rect this problem in his patients (verbal communication during course; Charles Casebeer, MD, January 1995).
Clinical Trials in Progress In December 1995, Ibrahim and colleagues 13 published the results oftheir first 107 eyes in 73 patients. The article was not published in time to receive methodologic review for this assessment; it will receive methodologic review in early 1996. The abstract states that 14% of eyes lost two to five lines of spectacle-corrected vision. Stephen G. Slade, MD, Assistant Clinical Professor, University of Texas-Houston, and co-workers have sub mitted for peer-review their results of 100 patients with ALK for myopia using a cap rather than flap primary lamellar cut. Daniel S. Durrie, MD, Assistant Clinical Professor, University of Nebraska, and co-workers retrospectively are collecting 1000 patients with ALK, including 100 from each of ten centers. The patients will be a mix of those who have had ALK for myopia and ALK for hyperopia. Richard W. Yee, MD, Clinical Associate Professor, University of Texas-Houston Health Science Center, is preparing a multicenter study on the incidence of com plications encountered during a surgeon's initial experi ence with ALK. Frank Price, MD, 14 has published an article describing the occurrence of central islands of steepening in six eyes
offour patients in a total of43 ALK procedures performed on 32 patients. Dr. Price 15 has published a second article describing results of 158 eyes with at least a 6-month fol low-up after myopic ALK. Richard Lindstrom, MD, and David Harden, MD, are preparing for publication their first 265 consecutive pa tients who have had ALK for myopia and 44 who have had ALK for hyperopia. Additional studies of ALK were presented both at the American Academy of Ophthal mology's Annual Meeting in November 1995 and at the pre-Academy Meeting of the International Society of Re fractive Surgery in Atlanta, Georgia. These studies should reach the peer-review literature in 1996. Drs. Ronald Marks and Harold Sawelson have sub mitted two articles to Ophthalmology entitled "Influence of the Learning Curve for Automated Lamellar Kerato plasty" and "One-year Results of Automated Lamellar Keratoplasty." A study on the Emory University expe rience with ALK also is undergoing peer review.
Summary The Academy finds in its preliminary review of kerato mileusis in situ and ALK reason for more rigorous eval uation of the safety, refractive accuracy, stability, and op tical quality of these microkeratome-based procedures. To understand these issues more thoroughly, the ophthalmic community needs continued access to peer review literature of sufficient quality to answer the ques tions posed earlier in this preliminary assessment.
Preparation was coordinated by the Committee on Ophthalmic Procedures Assessment, with the help of the following:
1995 Committee on Ophthalmic Procedure Assessments:
1995 COPA Refractive Surgery Panel:
* Proprietary Interests Leo J. Maguire III, MD (Chair) George B. Bartley, MD Elisabeth J. Cohen, MD DonaldS. Fong, MD, MPHt Stephen C. Gieser, MD, MPH Donald P. Maxwell, Jr., MD Christopher J. Rapuano, MD
N ________________ N _______________ N ________________ N _______________ N ________________ N _______________ N _______________
Christopher J. Rapuano, MD (Chair) Peter J. Agapitos, MD William W. Culbertson, MD Vincent P. de Luise, MD Douglas D. Koch, MD
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Ophthalmology 1995 Refractive Surgery Interest Group Executive Committee:
Volume 103, Number 5, May 1996
Peter J. McDonnell, MD (Chair) H. Dunbar Hoskins, Jr., MD Douglas D. Koch, MD Manus C. Kraff, MD Paul R. Lichter, MD Richard L. Lindstrom, MD Marguerite B. McDonald, MD Richard P. Mills, MD Roger F. Steinert, MD R. Doyle Stulting, MD, PhD
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Edited by:
Susan Garratt
N ________
Managing Editor:
Becky Anderson, Project Manager
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Approved by:
Board of Trustees, November 1995
I,Cl _ _ _ _ __ Pc, I, C2, C3, C5, C6, C7, C8
N _ _ _ _ _ __ N _________ N _ _ _ _ _ _ __
* Proprietary Interests Stated: t Served as the methodologist for this PPA
CATEGORY ABBREVIATION SPECIFIC FINANCIAL INTERESTS
Investor
p Pc I
Consultant
c_
Product
Ic
Cc __
None
Cl C2 C3 C4 C5 C6 C7 C8 N
or Ccl or Cc2 or Cc3 or Cc4 or Cc5 or Cc6 or Cc7 or Cc8
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.
References 1. O'Day DM, Steinberg EP, Dickersin K. Systematic literature review for clinical practice guidelines. Trans Am Ophthal mol Soc 1993;91:421-40. 2. Powe NR, Tielsch JM, Schein OD, et a!. Rigor of research methods in studies ofthe effectiveness and safety ofcataract extraction with intraocular lens implantation. Arch Ophthalmol 1994; 112:228-38. 3. American Academy of Ophthalmology. Keratophakia and keratomileusis: safety and effectiveness, Ophthalmic Pro cedures Assessment. Ophthalmology 1992;99: 1332-41.
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4. Maguire U. Keratorefractive surgery, success, and the public health. Am J Ophthalmol 1994; 117:394-8. 5. Crews KR, Mifflin MD, Olson RJ. Complications of au tomated lamellar keratectomy. Arch Ophthalmol 1994;112: 1514-5. 6. Hoffman CJ, Rapuano CJ, Cohen EJ, Laibson PR. Dis placement of corneal lenticule after automated lamel lar keratoplasty. Am J Ophthalmol 1994;118:109 11. 7. Binder PS, Akers PH, Deg JK, eta!. Refractive keratoplasty. Microkeratome evaluation. Arch Ophthalmol 1982; 100: 802-6. 8. Krueger RR, Talamo JH, McDonald MB, et a!. Clinical
American Academy of Ophthalmology · Automated Lamellar Keratoplasty analysis of excimer photorefractive keratectomy using a multiple zone technique. Am J Ophthalmol 1995; 119:263 74. 9. Hofmann RF, Bechara SJ. An independent evaluation of second generation suction microkeratomes. Refract Corneal Surg 1992;8:348-54. 10. Stonecipher KG, Parmley VC, Rowsey JJ, eta!. Refractive corneal surgery with the Draeger rotary microkeratome in human cadaver eyes. Refract Corneal Surg 1994; 10:49 55. II. Bas A, Nano H. In-situ myopic keratomileusis results in 30 eyes at 15 months. Refract Corneal Surg 1991 ;7:223-31.
12. Arenas-Archila E, Sanchez-Thorin JC, Naranjo-Uribe JP, et a!. Myopic keratomileusis in situ: a preliminary report. J Cataract Refract Surg 1991;17:424-35 . 13. Ibrahim 0, Waring GO III, Salah T, El Maghraby A. Au tomated in situ keratomileusis for myopia. J Refract Surg 1995;11:431-41. 14. Price FW. Central islands of corneal steepening after au tomated lamellar keratoplasty for myopia. J Refract Surg 1996; 12:36-41. 15. Price FW, Whitson WE, Gonzales JS, Gonzales CR, Smith J. Automated lamellar keratomileusis in situ for myopia. J Refract Surg 1996; 12:29-35.
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Automated Lamellar Keratoplasty American Academy of Ophthalmology * The purpose of the Committee on Ophthalmic Procedures Assessments is to eval uate on a scientific basis new and existing ophthalmic tests, devices, and procedures for their safety, efficacy, clinical effectiveness and appropriate uses. Evaluations include examination of available literature, epidemiological analyses when appropriate, and compilation of opinions from recognized experts and other interested parties. After appropriate review by all contributors, including legal counsel, assessments are submitted to the Academy's Board of Trustees for consideration as official Academy policy.
Introduction to Preliminary Procedure Assessments The rapid integration of successful new technology into ophthalmic practice is a complex process. Industry must market the emerging technology fairly and accurately. It is the responsibility of innovators and early adaptors to plan well-designed studies and present prompt, accurate, and comprehensive results in peer-review journals. The limitations and benefits of the new technology can be evaluated fairly only when these studies are well executed and reported in a timely fashion. Judgments are less likely to be correct when study design is poorly conceived, mar keting claims are inaccurate, and peer-review information is delayed or nonexistent. Recent methodologic reviews of the literature of cat aract extraction 1•2 and the review of keratomileusis and keratophakia by the American Academy of Ophthalmol ogy showed apparent deficiencies in the rigor of research methods used to evaluate the safety and efficacy of in novative ophthalmic technology. These studies concluded that ophthalmologists should improve the rigor ofresearch in ophthalmic surgery. That improvement will require more careful attention to fundamental principles ofstudy design, data analysis, and reporting. In response, the Academy has designed the Prelim inary Procedure Assessment (PPA) to complement the Prepared by the Committee on Ophthalmic Procedures Assessment and approved by the American Academy ofOphthalmology's Board ofTrus tees, November 1995.
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standard Ophthalmic Procedures Assessment that it has provided its members since 1982. 3 The preliminary assessments begin the evaluations earlier to help define the questions to be answered before more formal methodologic reviews take place. These assessments also provide feedback to industry and clinicians in vestigating new technology so that they can improve the quality of their data collection and presentation before the standard assessment proceeds. The goals of the preliminary assessment are to improve the effi ciency of innovation of new products and procedures, and to aid all parties interested in an objective eval uation of these new technologies. To accomplish these goals, the preliminary assessments in general are intended to do the following: • Describe the theoretical or scientific basis for opti mism about the emerging technology. • Summarize and complement the information that industry presents on emerging and innovative ophthalmic procedures. • Test the accuracy of marketing claims and identify questions that require careful and detailed scientific investigation before the procedure should be consid ered safe and effective. • Critically review the current literature in the field. • Describe clinical trials in progress and present antic ipated dates of study completion. The American Academy ofOphthalmology emphasizes that the preliminary assessment document is only one of the expected outcomes of the assessment process. Another
American Academy of Ophthalmology · Automated Lamellar Keratoplasty outcome is the establishment of more rigorous research methods. This pilot assessment on automated lamellar keratoplasty (ALK) generated debate among a wide range of experts, from creative innovators to methodologists. As consensus based on current scientific literature strengthened, most innovators saw the need to improve the quality of their science and suggested that methodol ogists, scientists, and innovators work together to generate more rigorous protocols to answer questions of interest to the patient. Reviewers also saw the need to analyze new articles on ALK very soon after publication so that this document does not become obsolete instantly. It is anticipated that these suggestions will soon tum into real ity so that the Academy membership and the public re ceive the credible analysis of new technology they desire.
The Automated Lamellar Keratoplasty Preliminary Procedure Assessment The Academy selected ALK as the topic for the first PPA for a number of reasons. The technology has promise in the correction of high myopia and perhaps also hyperopia. Lamellar technology is evolving from earlier microkera tome systems that were associated with clinically signifi cant complications. 3 Significant challenges remain in finding safe and efficacious methods for the surgical cor rection of high myopia and hyperopia. A large number of alternative procedures have been proposed and are under investigation, including clear lens extraction, phakic intraocular lenses, excimer laser pho torefractive keratectomy, laser in situ keratomileusis, and automated lamellar keratoplasty. The peer-review litera ture contains a paucity of information on the relative safety and efficacy of these competing approaches. The literature does demonstrate that patients with severe re fractive errors are often highly motivated to correct their problem surgically. Many patients will consider the sur gery a success, even if severe degradation of night vision and other problems related to optical quality develop. 4 There is reason to suspect that automation in the new technology may not completely eliminate some of the complications, and there is reason to suspect that problems will occur with optical quality that are independent of refractive accuracy, especially night aberration. 4 •5 Automated lamellar procedures have been heavily marketed in nonpeer-review literature, but peer-review articles on clinical results were almost nonexistent as of October 1995. 5•6 Because the older microkeratomes pre dated the Federal Drug Administration (FDA) regulatory approval process, current microkeratome systems are said to be equivalent and are "grandfathered" in without re view. The ophthalmic community will be better able to evaluate this technology if the leaders in innovation pres ent data in a framework that convinces others that the technology has a clinically acceptable level of safety and efficacy. This document will not analyze laser in situ keratom ileusis. That surgical technique will be the subject of a later PPA.
Historical Background Automated lamellar keratoplasty represents the newest in a series of surgical techniques in keratorefractive surgery to evolve from the work of Castroviejo and Barraquer, 3 who performed the earliest studies with the microkera tome-the instrument that is common to all these tech niques. These early researchers designed and later updated this instrument to remove a disc of the anterior corneal stroma so that they could lathe it, resuture it to the corneal surface, and thereby alter refractive error. Throughout the late 1980s, the primary procedures under investigation were keratomileusis and keratophakia. The Academy's 1992 Ophthalmic Procedures Assess ment entitled Keratomileusis and Keratophakia: Safety and Effectiveness, describes the peer-review literature ex tant through the late 1980s. 3 It concluded that these pro cedures had a small, well-defined role in the surgical man agement of high refractive errors, whether myopic or hy peropic. Although a large number of surgeries were performed, few well-controlled studies existed. Reported complication rates were significant and serious in some studies. Even skilled surgeons had visually significant complications in 1% to 14% of patients. The major prob lems included the complexity of the procedure and equipment, the delayed visual rehabilitation, the potential for mild to severe loss of Snellen visual acuity, decrease in quality of vision from glare, Joss of contrast sensitivity, inaccuracy of refractive results, and postoperative com plications involving principally re-epithelialization and wound healing. The 1992 assessment also concluded that well-designed prospective studies were needed to evaluate these techniques objectively so that they could be com pared with surgical alternatives for the correction of high myopia and high hyperopia.
Scientific Basis for Renewed Optimism for Microkeratome-based Systems Changes in Microkeratome Design A perfect microkeratome system would give predictable lamellar sections. The sections would invariably be well centered. The lenticule would be of appropriate thickness and diameter. The interface would show a smoothly cut surface rather than periodic nonuniform incisions caused by vibration-induced chatter ofthe microkeratome blade. The micro keratome blades would be of high quality and show flawlessly honed blade surfaces without fracture lines, debris, or score lines. The nonautomated microkeratome did not consistently meet these criteria. The depth of cut was variable. Ex perienced surgeons inadvertently entered the anterior chamber in 1% to 2% of patients, despite a predicted in cision depth of 130 to 160 ~-tm. Clinical studies note discs with diameters that were smaller than the predicted size to such a degree that they Jed to clinically significant re duction of visual acuity in 2% to 3% of patients. 3 Risto
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logic findings also showed characteristic nonsmooth in terfaces (chatter) caused by blade vibration. 7 Fast passage of the microkeratome over the surface gave superficial cuts; slow passage gave deeper cuts. There is renewed interest in keratomileusis as ophthal mologists search for an effective means to correct higher amounts of myopia (> -6.0 diopters). Excimer laser trials on this higher myopia group show poorer predictability, more postoperative scarring, greater refractive regression, and more severe visual aberrations when compared with results of similar trials for lower amounts of myopia (<6.0 diopters). 8 While excimer trials progressed, micro kera tome manufacturers improved the quality of the micro keratome systems. Some manufacturers have automated their systems to allow the keratome to pass over the cor neal surface without the surgeon controlling it, because they believed the manual pass caused many of the prob lems with the earlier systems. 9 •10 The quality of micro keratome blades also is improved. The new automated microkeratomes are designed to approximate more closely the criteria of an ideal microkeratome.
Changes in Microkeratome-based Procedures Keratomileusis In Situ for Myopia. This procedure flat tens the central cornea by excising and discarding a vol ume of stroma located between the superficial and deep stromal lamellae. The excised area is centered over the pupil and is 3.5 to 5.0 mm in diameter. The thickness and diameter of the excised stromal lenticule determine the amount of myopia corrected. Early investigators ex posed the surgical field for the lenticule resection by tem porarily displacing from the central cornea a free disc of anterior stroma 160 ~m thick and 7.2 mm in diameter (Ruiz and Rowsey; presented as an abstract at the ARVO Annual Meeting, Sarasota, 1988). After discarding the deeper stromal lenticule, the anterior stromal disc con formed to the base of the excision site and the disc's an terior surface flattened as well. The anterior stromal free disc has now been replaced with an anterior stromal flap. The flap has the same di ameter as the disc used in earlier procedures. It differs from a disc in that it remains attached to bordering an terior stroma for approximately 30° of its circumference. Some researchers are investigating whether flap thickness should be reduced to 130 ~m rather than the 160-~m thickness used in earlier studies. Keratomileusis In Situ for Hyperopia. Ruiz observed steepening of the anterior corneal curvature when the stromal thickness of a micro keratome pass exceeded 60% of the central corneal thickness (written communication; Charles Casebeer, MD, January 1995). The unresected stroma deep to the resection bulged forward as a result of the overlying resection. When the flap was re-approxi mated to the ectatic deeper stroma, it conformed to ectasia induced by the resection. The anterior curvature of the flap steepened as a result. The amount of steepening is controlled by the diameter of the cut. Progressive myopic shift may result.
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Automated Lamellar Keratoplasty. Automated la mellar keratoplasty is the name given to the in situ ker atomileusis procedure performed with the newly designed automated microkeratomes.
Marketing Marketing Claims and Their Implications Promotional material from Chiron Vision (Irvine, CA), the main microkeratome marketer, promises standardized quality: ". . . precise corneal discs of preselected thickness and diameter . . ." and a ". . . dramatic increase in the accuracy of the cut." These promotional handouts indi cate that the microkeratomes allow the user to ". . . cut a precise corneal disc of preselected thickness and di ameter-accurately." The handouts state, "The keratec tomy is now performed with the same exact movement every time, with every surgeon." ' The Summer 1995 issue ofthe Casebeer System Update states, "Automated Lamellar Keratoplasty is proving to be an extremely valuable procedure. We have made many improvements to the procedure resulting in better pre dictability and safety. It is now apparent, for a variety of reasons, that ALK is an essential part of the armamen tarium of a surgeon who chooses to be a comprehensive keratorefractive surgeon." Figure 1, which was first gen erated in 1993, shows that the Casebeer system suggests ALK as one of two alternatives to correct 1 to 6 diopters of hyperopia and 5 to 35 diopters of myopia. If the marketing claims are correct and the microker atomes do give consistent, accurate results every time, then the technology is more likely to obtain reproducible results. Any initial errors in refractive accuracy should require simple adjustments in the nomograms. If the claims are not correct, however, results with any micro keratome-based procedures will be heterogeneous, equip ment failures will occur that could threaten vision 3•5 no mograms will not be easy to adjust, and a greater 'risk of inaccurate corrections and degraded optical performance will be incurred. 4 •5
Evaluating the Accuracy of Marketing Claims To test the accuracy of marketing claims about the im proved accuracy and predictability ofcuts from automated microkeratomes, answers to the following questions are necessary: • How is each component ofthe lamellar disc (interface smoothness, accuracy, and reproducibility of disc diameter; accuracy and reproducibility ofdisc thick ness) affected by automating the pass ofthe micro keratome? • Do microkeratomes produce primary (superficial flap) and secondary (refractive power lenticule) cuts of equal reproducibility and quality? • How often can one expect equipment-related failure with the newer technology? What are the clinical consequences of mechanical failure?
American Academy of Ophthalmology
Automated Lamellar Keratoplasty
+6 +5 +4 +3 +2 +1 0 -1 -2 -3 -4 -5 -6 -7 -8 -9 -10 -11 -12 -13 -14 -15 -16 -17 -18 -19 -20 -21 -22 ...... -30
Astigmatism +6 +5 +4 +3 +2 +1 0
Figure 1. Marketing nomogram from the Casebeer Comprehensive Refractive Surgeon Nomogram. (Reprinted from Casebeer JC, Slade S: The Comprehensive Approach to Keratorefractive Surgery. Unpublished course material. Scottsdale, AZ; 1993.) AK = astigmatic keratotomy; LASIK = laser in situ keratomileusis; RK = radial keratotomy; ALK = automated lamellar keratoplasty; PRK = photorefractive keratectomy.
• What is the learning curve for microkeratome-based systems? • Does literature exist to allow one to compare the quality of the primary and secondary resections of competing automated microkeratomes? What should be the minimal acceptable measurement criteria for such a study?
•
To test the accuracy of marketing claims about clinical results with automated microkeratomes, answers to the following questions are necessary:
•
• What studies prove that ALK gives superior results in optical quality, refractive accuracy, and rates of serious complications when compared with manual pass keratomileusis in situ? • What are the most common complications observed (and reported rates of occurrence) with automated microkeratome systems? • Do vision-threatening complications occur with au tomated microkeratome systems? • Does ALK cause a higher rate of degraded optical quality and refractive instability in patients with pre vious refractive surgery? • Can permanent central artery occlusion occur as a result of the high intraocular pressure generated by the microkeratome's suction device? • What are the inherent problems likely to remain with microkeratome-based systems, regardless of the
•
• • • • •
quality and reproducibility ofthe microkeratome in cisions? How does the optical quality of ALK surfaces (e.g., size of uniform optical zone, centration, ir regular astigmatism) compare with optical quality after radial keratotomy, excimer laser photore fractive keratectomy, and laser in situ keratomi Jeusis? How do results compare with photorefractive kera tectomy in the same refractive range? With radial keratotomy in the same refractive range? Do refractive results stabilize in all cases of ALK for myopia and ALK for hyperopia? Does ALK cause a higher rate of degraded optical quality and refrac tive instability in patients with previous radial ker atotomy than it does in patients without previous refractive surgery? What are the rate and variability of visual recovery? Is there a difference in visual acuity, refractive results, astigmatism, and complications ofthe free-cap versus hinged-cap techniques? What is the refractive accuracy of ALK before en hancement surgery? How frequently are patients left with clinically sig nificant distortion of central vision"r-6 How frequently are patients left with clinically sig nificant aberration of peripheral vision? Of night vi sion"r-6
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• What percentage of patients with subjective com plaints of severe night vision disturbance, glare, or halos are nevertheless happy with the overall result of ALK? • Are results stable over the long term? Is long-term stability affected by incisional enhancement surgery? • Is there a greater risk of postoperative complica tions in patients with previous radial keratotomy than in patients with no previous refractive sur gery? How often will ocular trauma lead to dis placement of the ALK flap or cap? What are the visual sequelae of these displacements? How often will ocular trauma lead to globe perforation in pa tients requiring radial keratotomy or relaxing in cision after ALK?
Review of Nascent Literature Studies Comparing the Accuracy and Reproducibility of Discs, Flaps, and Stromal Lenticules Obtained by Automated and Nonautomated Keratomes during Keratomileusis In Situ Clinical Studies. No published peer-review studies were found in the literature review on this subject as of October 1995. Eye Bank Studies. In the absence of clinical studies, eye bank studies offer the best, albeit imperfect, answers to some of the questions raised above. Eye bank eyes are not dynamic. There may be differences in lamellar integ rity. Intraocular pressure may be difficult to control. Eye bank studies do not have to deal with the suction problems of narrow intraorbital fissures and redundant conjunctiva that occur in a subset of patients. The eye bank study performed by Hofmann and Bechara9 compared two automated microkeratomes with a second-generation microkeratome that bad a manual drive. The component parts are shown in Table 1. Each system performed five keratomileusis in situ primary ker atectomies, five secondary 100-.um keratectomies, and one deep (400-.um) lamellar keratectomy. The study evaluated the surface characteristics of the keratectomy sites as well as the accuracy of the diameter and thickness of the la mellar keratectomies. The reviewing methodologist gave
the study an intermediate rank for scientific quality be cause the information was acquired from cadaver eyes. Hofmann and Bechara9 found that both the automated microkeratomes and the manual keratome produce cuts of nonuniform thickness (chatter). The hand-advanced system showed an irregular pattern of chatter, whereas the chatter lines in the two automated systems were ar ranged parallel to the edge of the blade and had a regular pattern. Reproducibility of Disc Thickness and Diameter during Primary Keratectomy. Hofmann and Bechara9 observed that the mean section diameters were 10% to 20% smaller than the predicted diameter of 7.2 mm for all three microkeratomes. The Steinway instrument (Chi ron Vision) tended to generate stromal discs thicker than predicted, whereas the other instruments tended to gen erate discs thinner than predicted. All three microkera tomes showed a range of deviation from predicted thick ness of more than 20 ,urn. Reproducibility of Disc Thickness and Diameter during Secondary Keratectomy. Hofmann and Bech ara9 noted that the diameters ofthe secondary keratectomy showed a variation from the predicted diameter of 6% for the Steinway automated microkeratome, 9% for the Draeger Lamellar Keratome (Storz Instrument GmbH, Heidelberg, Germany), and 25% for the manual keratome. Hofmann and Bechara9 observed the variability in the thickness of the lenticule resections. The Steinway auto mated microkeratome tended to cut thicker sections than predicted, and the other systems tended to cut thinner sections than predicted. The range of deviation from pre dicted thickness was 22 .urn for the Stein way instrument, 24 .urn for the manual microkeratome, and 7.8 .urn for the Draeger instrument.
Peer-review Literature on Keratomileusis In Situ and Automated Lamellar Keratoplasty Keratomileusis In Situ. Two peer-review articles on keratomileusis in situ using nonautomated microkera tomes were identified 11 • 12 (see Table 2). Both reports were published in 1991 on surgery performed in the late 1980s with older microkeratome designs. The methodologist re viewing these artilces gave each study a low rating for scientific content. The low rating was based on three fac tors: ( 1) the results were not reported at a defined post-
Table 1. Comparison of Component Parts of Microkeratomes Tested by Hofmann and Bechara9 Model Name Component Parts Motor Blade movement Adjustable suction ring Change of depth plate Movement across cornea
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Steinway (automated corneal shaper)
Draeger (automated lamellar keratome)
Microprecision Test Model
Electric Oscillating Yes Interchangeable plates Mechanical: gear driven
Electric Rotary
Gas turbine Oscillating
No Interchangeable plates Mechanical: screw driven
No Adjustable screw Manual
American Academy of Ophthalmology · Automated Lamellar Keratoplasty Table 2. Results of Keratomileusis In Situ with Nonautomated Microkeratomes Peer-review Article #l Bas and Nano, 1991 Prospective No 30/17 Myopia, > -8.00 D Astigmatism, < 5.00 D Age,> 20 yrs Keratometry, 40-47 D Central corneal thickness, 0.50-0.70 mm Steinway Barraquer IBM-PC Diameter, 6.5-8.0 mm Thickness, 0.10-0.18 mm Diameter, 3.25-5.00 mm Thickness, 0.08-0.20 mm 11
Type of study Institutional review board approved No. of eyes/patients Entry criteria
Microkeratome Nomogram First-pass parameters Stromal resection Cap fixation
Antitorque suture
Intraoperative Complications First pass Inaccurate thickness Disc rupture Decentration Inaccurate diameter
NA 1/30 3/30 NA
Jammed keratome Stromal resection Inaccurate thickness
Arenas-Archila et a!, 1991 12 Prospective No 32/17 Myopia,> -4.5 D Astigmatism, NA Age,> 19 yrs Keratometry, > 39.25 D Corneal thickness, > 0.52 mm Barraquer Ruiz Diameter, 7.2 mm Thickness, 0.180-0.200 mm Diameter, 4.2 mm Thickness, 0.05-0.20 mm, depending on intended correction Antitorque suture
In slightly less than· 50% 1/32 NA "Routinely" close to calculated 7.2-mm diameter, but no documentation 1/32
NA 3/30 (required second resections)
28/32 inaccurate 9 require second stromal resection 2 require total stromal resection "Irregular oval shape in almost every case" 1/32 decentered resection with edge bisecting pupil
Inaccurate diameter Decentration
NA NA
Jammed keratome
NA
0/32
NA 3/30 4/30 7/30 7/30 monocular diplopia at night 1 allograft disc for disc rupture 4 radial keratotomies for undercorrection 1 removal of large epithelial implantation 10/30 required 6 mos to achieve best vision Cannot evaluate; many amblyopic preoperatively 6/30 amount and time course of regression not documented
1/32 when cap placed epithelial side down 2/32 3/32 NA NA 1 reposition of epithelial side down graft 1 repeat myopic keratomileusis in situ 55 days after healing of ruptured disc NA
Postoperative Complications Severe interface opacity Minor interface opacity Epithelial implantation "Irregular astigmatism" Night aberration Secondary procedures Delayed visual recovery Two or more lines loss of vision Late refractive regression Refractive Accuracy Time of report Manifest within 1 D Manifest within 2 D Manifest > 5 D from emmetropia Type of refraction D
Peer-review Article #2
=
diopter; NA
=
360-540 days after surgery 8/30 19/30 6/30 Manifest
8/32 NA 90-194 days after surgery 3/16 from -10- to -21-D group 8/16 from -10- to -21-D group 6/15 from -5.25- to -9.75-D group 10/16 from -10- to -21-D group 10/16 from -5.25- to -9.75-D group Cycloplegic
not available.
operative time; (2) both eyes were included from single patients, which interfered with the randomness of the study; and (3) the studies reported on mean visual acuity instead of on the fraction of patients achieving a defined level of visual acuity.
A review of Table 2 shows significant problems with microkeratome resections, especially the stromal resec tions. These results corroborate the eye bank data, which show a less reproducible second microkeratome pass (lenticule excision). Refractive accuracy is less than
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Ophthalmology Table
3. Summary of Complications Associated with Automated Microkeratomes
Decentered ablations Cap melts Holes in caps Nonadherent caps Recurrent corneal erosion Infection Ectasia associated with refractive regression Loss of two or more lines of visual acuity Interface scarring Large overcorrection Large undercorrection Noncircular secondary lamellar resections
adequate (range, 20%-63%; >5 diopters from emme tropia postoperatively). Complications are high enough for the authors of one of the articles to conclude that " . . . in our hands, myopic keratomileusis in situ was not a technically safe, precise and predictable technique for the correction of myopia. Further improvements in the technique and equipment may provide better re sults." 12 Automated Lamellar Keratoplasty for Myopia. No articles on this procedure were identified in the peer-review literature as of October 1995. Studies submitted for pub lication and in progress are described in the following section on clinical trials in progress. It remains unclear how well the studies will answer the questions posed until results are published and undergo content and method ologic review. Abstracts on ALK were presented at the International Society of Refractive Surgery (formerly In
Table Case No. 1 2 3
4
5
6 7 8 9 10 11 12
Indication for ALK Myopia Myopia Hyperopia Myopia Myopia Myopia Myopia Hyperopia Myopia Myopia Myopia Myopia
4.
Months Cap in Place <1 17 16 7
3 2 3 4 <1 6
ternational Society of Refractive Keratoplasty) Meeting in San Francisco in October 1994. Table 3 shows the list of complications associated with the automated systems based on a review of all abstracts on keratome-based pro cedures. Schneider and colleagues evaluated 66 eyes 6 months after ALK for myopia (presented as an abstract at the ARVO Annual Meeting, Ft. Lauderdale, 1995). Fifty-four percent of patients showed uncorrected visual acuity of 20/40 or better, but 22% of patients lost two or more lines of best-corrected visual acuity. The number of patients who required secondary procedures to obtain 20/40 visual acuity without correction were not identified, nor was night vision disability discussed. Mamalis and colleagues report in an extended abstract on 12 corneal caps removed from 12 patients after ALK (see Table 4) (American Society of Cataract and Refractive Surgery Symposium of Cataract, IOL, and Refractive Sur gery, Boston, 1994). The caps were obtained over a 6-month period. All patients had surgery using the cap rather than flap technique. Seven ofthe removed caps were from patients with refractive procedures before the ALK procedure. The authors of the abstract could not document the incidence of cap complications because the caps were received from an undisclosed number of surgeons performing an undis closed number of procedures. Final visual outcome is not discussed, because this abstract dealt with the histopathologic findings of failed or removed caps. Automated Lamellar Keratoplasty for Hypero• pia. The peer-review literature contains no articles on ALK for hyperopia. Studies submitted for publication and currently under way are described in the following section. It remains unclear how well the studies will answer the questions posed until results are published. According to instructors of the January 1995 Chiron Vision course on ALK for hyperopia, progressive ectasia,
Patient Characteristics* Complication
Cap Disposition
Dislocated cap Irregular astigmatism Irregular astigmatism Irregular astigmatism Irregular astigmatism Irregular astigmatism Epithelial ingrowth Suspected infection Irregular astigmatism Fragmented cap Haze Dislocated cap
Fell off Removed Removed Removed Removed Removed Removed Removed Removed Fell off Removed Fell off
Other Prior Surgical Procedure PKP RK, cap sutured RK RK RK Cap sutured RK Excimer RK
• Source: Mamalis N, Lucius R W, Casebeer C. Histopathologic analysis of cornea caps removed after automated lamellar keratoplasty. American Society of Cataract and Refractive Surgery Symposium of Cataract, IOL, and Refractive Surgery; Boston; 1994. ALK = automated lamellar keratoplasty; PKP = penetrating keratoplasty; RK = radial keratotomy.
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American Academy of Ophthalmology · Automated Lamellar Keratoplasty myopia, and irregular astigmatism have been observed among a subgroup of patients when the stromal thickness of the microkeratome pass exceeds 80%. Ruiz has per formed more than 200 penetrating keratoplasties to cor rect this problem in his patients (verbal communication during course; Charles Casebeer, MD, January 1995).
Clinical Trials in Progress In December 1995, Ibrahim and colleagues 13 published the results oftheir first 107 eyes in 73 patients. The article was not published in time to receive methodologic review for this assessment; it will receive methodologic review in early 1996. The abstract states that 14% of eyes lost two to five lines of spectacle-corrected vision. Stephen G. Slade, MD, Assistant Clinical Professor, University of Texas-Houston, and co-workers have sub mitted for peer-review their results of 100 patients with ALK for myopia using a cap rather than flap primary lamellar cut. Daniel S. Durrie, MD, Assistant Clinical Professor, University of Nebraska, and co-workers retrospectively are collecting 1000 patients with ALK, including 100 from each of ten centers. The patients will be a mix of those who have had ALK for myopia and ALK for hyperopia. Richard W. Yee, MD, Clinical Associate Professor, University of Texas-Houston Health Science Center, is preparing a multicenter study on the incidence of com plications encountered during a surgeon's initial experi ence with ALK. Frank Price, MD, 14 has published an article describing the occurrence of central islands of steepening in six eyes
offour patients in a total of43 ALK procedures performed on 32 patients. Dr. Price 15 has published a second article describing results of 158 eyes with at least a 6-month fol low-up after myopic ALK. Richard Lindstrom, MD, and David Harden, MD, are preparing for publication their first 265 consecutive pa tients who have had ALK for myopia and 44 who have had ALK for hyperopia. Additional studies of ALK were presented both at the American Academy of Ophthal mology's Annual Meeting in November 1995 and at the pre-Academy Meeting of the International Society of Re fractive Surgery in Atlanta, Georgia. These studies should reach the peer-review literature in 1996. Drs. Ronald Marks and Harold Sawelson have sub mitted two articles to Ophthalmology entitled "Influence of the Learning Curve for Automated Lamellar Kerato plasty" and "One-year Results of Automated Lamellar Keratoplasty." A study on the Emory University expe rience with ALK also is undergoing peer review.
Summary The Academy finds in its preliminary review of kerato mileusis in situ and ALK reason for more rigorous eval uation of the safety, refractive accuracy, stability, and op tical quality of these microkeratome-based procedures. To understand these issues more thoroughly, the ophthalmic community needs continued access to peer review literature of sufficient quality to answer the ques tions posed earlier in this preliminary assessment.
Preparation was coordinated by the Committee on Ophthalmic Procedures Assessment, with the help of the following:
1995 Committee on Ophthalmic Procedure Assessments:
1995 COPA Refractive Surgery Panel:
* Proprietary Interests Leo J. Maguire III, MD (Chair) George B. Bartley, MD Elisabeth J. Cohen, MD DonaldS. Fong, MD, MPHt Stephen C. Gieser, MD, MPH Donald P. Maxwell, Jr., MD Christopher J. Rapuano, MD
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Christopher J. Rapuano, MD (Chair) Peter J. Agapitos, MD William W. Culbertson, MD Vincent P. de Luise, MD Douglas D. Koch, MD
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Ophthalmology 1995 Refractive Surgery Interest Group Executive Committee:
Volume 103, Number 5, May 1996
Peter J. McDonnell, MD (Chair) H. Dunbar Hoskins, Jr., MD Douglas D. Koch, MD Manus C. Kraff, MD Paul R. Lichter, MD Richard L. Lindstrom, MD Marguerite B. McDonald, MD Richard P. Mills, MD Roger F. Steinert, MD R. Doyle Stulting, MD, PhD
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Edited by:
Susan Garratt
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Managing Editor:
Becky Anderson, Project Manager
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Approved by:
Board of Trustees, November 1995
I,Cl _ _ _ _ __ Pc, I, C2, C3, C5, C6, C7, C8
N _ _ _ _ _ __ N _________ N _ _ _ _ _ _ __
* Proprietary Interests Stated: t Served as the methodologist for this PPA
CATEGORY ABBREVIATION SPECIFIC FINANCIAL INTERESTS
Investor
p Pc I
Consultant
c_
Product
Ic
Cc __
None
Cl C2 C3 C4 C5 C6 C7 C8 N
or Ccl or Cc2 or Cc3 or Cc4 or Cc5 or Cc6 or Cc7 or Cc8
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.
References 1. O'Day DM, Steinberg EP, Dickersin K. Systematic literature review for clinical practice guidelines. Trans Am Ophthal mol Soc 1993;91:421-40. 2. Powe NR, Tielsch JM, Schein OD, et a!. Rigor of research methods in studies ofthe effectiveness and safety ofcataract extraction with intraocular lens implantation. Arch Ophthalmol 1994; 112:228-38. 3. American Academy of Ophthalmology. Keratophakia and keratomileusis: safety and effectiveness, Ophthalmic Pro cedures Assessment. Ophthalmology 1992;99: 1332-41.
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4. Maguire U. Keratorefractive surgery, success, and the public health. Am J Ophthalmol 1994; 117:394-8. 5. Crews KR, Mifflin MD, Olson RJ. Complications of au tomated lamellar keratectomy. Arch Ophthalmol 1994;112: 1514-5. 6. Hoffman CJ, Rapuano CJ, Cohen EJ, Laibson PR. Dis placement of corneal lenticule after automated lamel lar keratoplasty. Am J Ophthalmol 1994;118:109 11. 7. Binder PS, Akers PH, Deg JK, eta!. Refractive keratoplasty. Microkeratome evaluation. Arch Ophthalmol 1982; 100: 802-6. 8. Krueger RR, Talamo JH, McDonald MB, et a!. Clinical
American Academy of Ophthalmology · Automated Lamellar Keratoplasty analysis of excimer photorefractive keratectomy using a multiple zone technique. Am J Ophthalmol 1995; 119:263 74. 9. Hofmann RF, Bechara SJ. An independent evaluation of second generation suction microkeratomes. Refract Corneal Surg 1992;8:348-54. 10. Stonecipher KG, Parmley VC, Rowsey JJ, eta!. Refractive corneal surgery with the Draeger rotary microkeratome in human cadaver eyes. Refract Corneal Surg 1994; 10:49 55. II. Bas A, Nano H. In-situ myopic keratomileusis results in 30 eyes at 15 months. Refract Corneal Surg 1991 ;7:223-31.
12. Arenas-Archila E, Sanchez-Thorin JC, Naranjo-Uribe JP, et a!. Myopic keratomileusis in situ: a preliminary report. J Cataract Refract Surg 1991;17:424-35 . 13. Ibrahim 0, Waring GO III, Salah T, El Maghraby A. Au tomated in situ keratomileusis for myopia. J Refract Surg 1995;11:431-41. 14. Price FW. Central islands of corneal steepening after au tomated lamellar keratoplasty for myopia. J Refract Surg 1996; 12:36-41. 15. Price FW, Whitson WE, Gonzales JS, Gonzales CR, Smith J. Automated lamellar keratomileusis in situ for myopia. J Refract Surg 1996; 12:29-35.
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