pachymetry, manual keratometry, and corneal topography by computerized ...... would guide the development of appropriate. RCTs. * Reconsideration of the use ...
EXCIMER LASER TREATMENT OF SPHERICAL HYPEROPIA: PRK OR LASIK?§ BY M. Samieh H. El-Agha, MD (BY INV'ITATION), Eic IV Johnston, MD (BY INVITATION), R. Wayne Bowman, MD (BY INV'ITATION), H. Dwight Cavanagh, MD, PhD (BY INVITATION), AND janes P McCulley, MD ABSTRACT
Purpose: To compare the efficacy and safety of photorefractive keratectomy (PRK) and laser in situ keratomileusis (LASIK) in the treatment of spherical hyperopia with use of the VISX STAR S2T"I excimer laser.
Methods: A review of 15 consecutive patients (22 eyes) receiving PRK and 22 consecutive patients (26 eyes) receiving LASIK (median follow-up, 12 months). Results: Mean age was 52 ± 7 years for patients receiving PRK and 55 ± 9 years for patients receiving LASIK. Mean preoperative spherical equivalent was +2.25 ± 1.16 D for PRK patients and +1.81 ± 0.92 D for LASIK patients. Mean deviation from intended correction was -0.82 ± 0.89 D after PRK and +0.19 ± 0.47 D after LASIK at 1 month (P 5 D), both H-PRK and H-LASIK have lower predictability and stability with a high rate of regression, and there is a high incidence of BSCVA Joss. 11 22-25 Fewer studies have examined differences between the 2 procedures in comparable groups. Ditzen and asscociates2' reported that H-LASIK for spherical hyperopia resulted in "less regression, minimal haze, and better predictability and stability than H-PRK." However, the study did not include an H-PRK group for direct comparison and relied on a historical control. Juhas and associates26 compared H-PRK and H-LASIK for 2 groups of spherical hyperopia (low, 3.5 D). The comparison was made at a single time point, 1 year after surgery. There were no statistically significant differences between both groups, but the investigators noted that H-LASIK was associated with greater safety, predictability, and stability, especially for the low hyperopia group.26 In our study, the most notable immediate difference between H-PRK and H-LASIK was the degree of postoperative pain. H-PRK was consistently associated with significant postoperative pain that required systemic medication in every case. Onset of pain after H-PRK was typically 36 hours after surgery, lasting up to 72 hours. This is in contradistinction to the pain following myopic PRK, which starts in the first few hours after surgery and lasts for 24 to 36 hours. The H-PRK patients were functionally incapacitated for 5 to 7 days after the procedure. In contrast to H-PRK, H-LASIK was associated with minor and transient discomfort that did not require systemic medication. Discomfort following LASIK occurred in the first few hours after surgery and was not incapacitating. Although there was a slightly higher proportion of eyes with UCVA of 20/40 or better in the H-LASIK group (Fig 2), this was not statistically significant. There was also a consistently higher proportion of patients in the HLASIK group with UCVA of 20/20 or better, and although the difference was more striking (Fig 3), it never reached statistical significance. It is also notable that UCVA steadily increased with time in both groups (Figs 2 and 3).
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Relatively poorer UCVA early after H-PRK may be partly due to transient corneal surface irregularities associated with epithelial healing.1' It may also be due to the temporary myopia caused by initial overcorrection. Predictability was judged by the proportion of cases within ± 0.50 D and ± 1.0 D of intended correction (Figs 4 and 5). Refractive stability was assessed by observing changes in the mean spherical equivalent (SE) of each group over time (Fig 6). It is notable that there was very little change in the mean SE of the H-LASIK group up to 12 months after surgery, with a mean regression of +0.016 D per month (mean SE at 1 month, +0.19 D; mean SE at 12 months, +0.37 D). In contrast, there was a significant myopic overshoot in the H-PRK group, which peaked at 1 month (mean SE, -0.82 D, P +6D).' As in previous studies involving low to moderate hyperopia,'9 we observed a very low incidence of haze after H-PRK in our study.
5.
CONCLUSION
15.
Our study shows that H-PRK and H-LASIK are comparable in terms of efficacy and safety for low to moderate hyperopia (up to 5D). However, H-PRK was associated with significant postoperative pain, an initial and temporary myopic overshoot that peaked at 1 month, and stability not occurring before 6 months after surgery. In contrast, H-LASIK was less painful and was associated with more rapid stability (at 1 month) and better UCVA (although this was not statistically significant). On the basis of these findings, we consider H-LASIK our procedure of choice for low to moderate hyperopia. Nevertheless, in cases where H-PRK would be more advantageous (eg, epithelial basement membrane dystrophy), H-PRK is a viable alternative to H-LASIK, but patients must be prepared for a more painful postoperative course, initial myopia, and relatively delayed refractive stability. REFERENCES
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Swinger CA. Comparison of results obtained with keratophakia, hypermetropic keratomileusis, intraocular lens implantation, and extended-wear contact lenses. Int Ophthalmol Clin 1983;23:59-74. Lyle WA, Jin GJ. Hyperopic automated lamnellar keratoplasty: Complications and visual results [see comments]. Arch Ophthaltmwl 1998; 116:425-428. Basuk WL, Zisman M, Waring GO III, et al. Complications of hexagonal keratotomy. Amii J Ophthalmol 1994;117:37-49. Alio JL, Ismail MM, Sanchez Pego JL. Correction of hyperopia with non-contact Ho:YAG laser thermal keratoplasty. J Refract Surg 1997;13:17-22.
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Brancato R, Carones F. Indications, results, and complications of refractive corneal surgery with lasers. Corr Opin Ophthalmlol 1994;5:90-97. Maloney RK, Friedman M, Harmon T, et al. A prototype erodible mask delivery system for the excimer laser. Ophthalmology 1993;100:542-549. Dausch D, Klein R, Schroder E. Excimer laser photorefractive keratectomy for hyperopia. Refract Conieal Surg 1993;9:20-28. Suarez E, Torres F, Duplessie M. LASIK for correction of hyperopia and hyperopia with astigmatism. Int Ophthalmitol Clin 1996;36:65-72. Dausch D, Smecka Z, Klein R, et al. Excimer laser photorefractive keratectomy for hyperopia [see comments]. J Cataract Refract Surg 1997;23:169-176. Danjoux JP, Kalski RS, Cohen P, et al. Excimer laser photorefractive keratectomy for hyperopia. J Refract Surg 1997;13:349-355. Jackson WB, Mintsioulis G, Agapitos PJ, et al. Excimer laser photorefractive keratectomy for low hyperopia: safety and efficacy. J Cataract Refract Surg 1997;23:480-487. O'Brart DP, Stephenson CG, Oliver K, et al. Excimer laser photorefractive keratectomy for the correction of hyperopia using an erodible mask and axicon system. Ophthalmrwlogy 1997;104:1959-1970. Brancato R, Carones F, Morico A, et al. Hyperopia correction using an erodible mask excimer laser delivery system coupled to an axicon: Preliminary results. EurJ Ophthalmol 1997;7:203-210. Sener B, Ozdamcar A, Aras C, et al. Photorefractive keratectomy for hyperopia and aphakia with a scanning spot excimer laser. J Refract Surg 1997;13:620-623. Vinciguerra P, Epstein D, Radice P, et al. Long-term results of photorefractive keratectomy for hyperopia and hyperopic astigmatism. J Refract Surg 1998;14:S183-185. Jackson WB, Casson E, Hodge WCG, et al. Laser vision correction for low hyperopia. An 18-month assessment of safety and efficacy. Ophthal7u,logy 1998;105:1727-1738; discussion 1737-1738. Carones F, Brancato R, Morico A, et al. Photorefractive keratectomy for hyperopia uising an erodible disc and axicon lens: 2-year results. J Refract Surg 1998;14:504-511. Corones F, Gobbi PG, Vigo L, et al. Photorefractive keratectomv for hyperopia: Long-term nonlinear and vector analysis of refractive outcome. Ophthalmology 1999;106:1976-1982; discussion 1982-1983. Knorz MC, Liermiann A, Jendritza B, et al. LASIK for hyperopia and hyperopic astigmatism--results of a pilot study. Seomin Ophthalmol 1998;13:83-87. Argento CJ, Cosentino MJ. Laser in situ keratomileusis for hyperopia [see comments]. J Cataract Refract Surg 1998;24:1050-1058. Rosa DS, Febbraro JL. Laser in situ keratomileusis for hyperopia. J Refract Surg 1999;15:S212-215. Arbelaez MC, Knorz MC. Laser in sittu keratomileusis for hyeropia and hyperopic astigmatism. J Refract Surg 1999;15:406-414. Pietila J, Makinen P, Pajari S, et al. Excimer laser photorefractive keratectomy for hyperopia. J Refract Surg 1997;13:504-510. Ditzen K, Huschka H, Pieger S. Laser in situ keratomileusis for hyperopia. J Cataract Refract Su rg 1998;24:42-47. Sener AB, Yanyali CA, Ozdamar A, et al. [Photorefractive keratectomy in hypermetropia]. J Fr Ophtalmrl) 1998;21:19-22. Juhas T, Kozak I, Augustinsky B. [Comparison of hyperopic photorefractive keratectomy and LASIK in correction of hypermetropia vith excimer laser]. Cesk Slov Oftalnool 1999;55:14-20. Reinstein DZ, Silverman RH, Sutton HF, et al. Very high-frequency ultrasound corneal analysis identifies anatomic correlates of optical complications of lamellar refractive surgery: Anatomic diagnosis in lamellar surgery. Ophthalmowlogy 1999;106:474-482. Hosoda Y, Nakayasu K. [A confocal microscopic and histological study oIn rabbit corneas after photorefractive keratectomy for hyperopial. Nippon Ganka Gakkai Zasshi 1999;103:243-251.
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Dierick HG. Van NIellaert CE, Missotteni L. Histology of rabbit coroea.s after 10-diopter photorefractive keratectomy for- hv\peropiai. J Refract Sirga 1999:115:459-468.
DISCUSSION
DR PENNY A. ASBELL. I wvant to acknowledge both Shawn Klein, MD, and Henry Sacks, PhD, MD, who assisted me in the preparation of this discussion, and I want to congratulate Dr McCulley and his co-authors for delivering the only paper-ever-that has attempted to present a direct comparison between txvo surgical methods to correct hyperopia. The authors conclude, essentially, that both H-PRK and H-LASIK can effectivelv correct low to moderate degrees of hyperopia, with similar results reported at 6 and 12 months post-operatively. Such a comparison, however, is clearly dependent on knowing that both groups, pre-operatively, were comparable. That was attempted here: * * * *
Same laser center Same laser Same surgeons (3) Consecutive cases
*
Similar demographics Similar spherical equivalents
*
On the other hand, potential significant sources of bias have not been totally eliminated, some of which are inherent in cohort studies of this stvle:
* * * * * *
Retrospective analysis Patient selection for treatment group Patients not randomized Observers not "blinded"
Incomplete data Accounting for loss to follow-up
The authors' presentation also masks several fascinating questions that may or not be significant: why is the percentage requesting monovision in PRK (5%) different from that in LASIK (31%)? WVhy was there such a high incidence of unilateral surgery in patients that were, presumably, hyperopic in both eyes 8 of 15 patients with HPRK and 18 of 22 patients with H-LASIK? Why was the incidence of pre-operative cylinder so much greater in the H-PRK patients (71%) than in those given H-LASIK (27o%)? The essential question, of course, is how should we be judging new devices and surgical interventions? For pharmaceuticals, we routinely rely on double-blind randomized controlled trials, but with surgery we have traditionally looked at case reports and reports on cohort
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series. Randomized clinical trials (RCT) were felt to be unethical, difficult to do (since vou could not "blind" the surgeon or the patient), subject to a significant learning curve that might influence any analysis of the data, lacking in standard protocols as techniques evolved and changed, and practically impossible to conduct because of the difficulty in recruiting patients. Is there any other way to approach this problem of how best to evaluate new surgeries? What about utilizing systematic overviews, using quantitative methods-the very definition of meta-analysis? Originally, meta-analysis was utilized to analyze a collection of published reports on randomized controlled trials which may have produced conflicting conclusions. More recently, these same statistical techniques have been applied to observational studies, such as the cohort study presented here by McCulley and group. The idea is that such systematic reviews can provide the best evidence for clinical decision making. Meta-analysis is powerful. It can increase statistical power for evaluating endpoints, resolve uncertainty Nwhen reports disagree, improve estimates of the effect of size, and answer questions that may not have been posed at the start of individual trials. WVe decided to attempt this approach to determine whether H-PRK or H-LASIK is better for treating hyperopia. \Ve failed, and here's why: The typical steps in a meta-analysis are the following: 1. Identification of relevant studies. WVe did computer searclhes to identify papers on H-PRK or H-LASIK that provided results on cohort studies in humans. 2. Quality assessment. This includes an evaluation of how the data are collected, evaluated, etc., and papers are often rated in a blinded fashion to determine includability. In our group, almost all papers found provided little information on how the study was done, the selection process used, accountability for all patients entered, and had many variables on surgical technique (laser used, parameters, microkeratome,
etc.). 3. Data extraction. WVe felt that there were 5 areas to evaluate to answer our clinical question: uncorrected visual acuity postoperatively; predictability as measured by residual refraction (+ 0.50 D, or ± 1.00 D); stability; adverse events (such as loss of best corrected visual acuity): patient assessment (glare, night vision, etc.). Almost all papers gave data on uncorrected visual acuity, but there the unanimity ended. 4. Statistical pooling. At this point in the ideal metaanalysis, the data collected would be pooled and
Excimiter Laser Treatmetnt of of Spherical Hyperopia
analyzed using any of several statistical methods. While we were willing to stretch the envelope a little by including incomplete data, poorly described methods, uncertain end points, large drop-out rates, and the like, these problems were overshadowed by the papers' fundamental flaw. The basic ingredient of all meta-analytic systematic reviews is that each paper must compare the same alternative treatments-drug A or drug B, or, in this case, H-PRK or H-LASIK. There must be a series of papers presenting withinstudy comparisons. The rationale for pooling results is that one is adding up within-study differences to determine whether differences are most likely due to the treatments rather than to anything else. So, as we now can all see, meta-analysis was not possible, given the typical cohort studies reported in the literature when discussing new medical devices and surgeries. The problem is not a new one. Chalmers, Buchwald and many others have noted that "the most universally acceptable and reliable means of assessing new patient therapies" is the RCT. With that in mind, some recommendations for medical device data reporting can be offered:
*
Uniform standards for collecting and reporting data, including defined key outcomes
*
Simultaneous cohort studies done prospectively by the same group of researchers. (Use of historical cohorts has been shown to bias results in favor the new treatment.)
*
Development of a national or international registry for collection of uniform data on patients undergoing treatment with alternative new devices or procedures-an interim source that would guide the development of appropriate RCTs.
*
Reconsideration of the use of RCT-still the best known way to define scientifically the worthiness of new treatments.
So, we have broken ground today. WVe hope the authors' paper is the first contribution in a trend toward better methodology for evaluating new surgical and device procedures in ophthalmology. DR MALCOLM L. MAZOWN'. I congratulate the authors on an excellent paper. As a strabismologist I am concerned about the possible development of intractable diplopia. In the past many patients with amblyopia who had suppression were operated on for their anisometropia by
radial keratotomy. Subsequently their angle of deviation changed, their suppression disappeared, and they developed intractable diplopia. Therefore I ask people who are doing refractive surgery to evaluate their patients before surgery to see if this is a possibility, one that they should attempt to avoid because we may not be able to eliminate their diplopia. DR INVAN R. SCHWTAB. I commend the authors for a careful evaluation of a procedure that is becoming very popular. One question is are we creating a public health problem? In a group whose average age is 55, a group in whom glare becomes a problem, contrast sensitivity decreases, and lens opacities may soon develop, are we creating a problem when they drive an automobile, particularly at night. Should we change our standards for driving an automobile? A second problem relates to glaucoma. We cannot satisfactorily evaluate the intraocular pressure with current devices when the cornea changes shape and thickness. The intraocular pressure is often underestimated with the tonopen. Furthermore now that the patients have good vision, they are less apt to return for routine evaluations. Are we going to create more problems with glaucoma in this group of treated patients? DR GEORGE L. SPAETH. First I have a question about the process of randomization. It is difficult to perform surgical studies that require randomization and keep them ethical, but it can be done and is often necessary. It has been done successfully for many studies in the treatment of glaucoma. My first question then is why not randomize the patients? How can one get meaningful data without randomization? My second question has to do with the development of cataracts induced by the use of postoperative steroids. Becker in the past and we, more recently, have shown that normal volunteers who were given steroid provocative tests with dexamethasone 4 times a day sometimes developed cataracts with significant reduction in vision. Was this problem looked for? DR VERINDER S. NIRANKARI. I have a different view regarding the possible problem mentioned regarding driving an automobile. Many of these patients cannot tolerate contact lenses. With strong glasses their vision is often not ideal. They may see better after refractive surgery. Were any of these patients preselected for PRK because of flat corneas, shallow anterior chambers, or corneal problems such as map-dot dystrophy? If so, did this make any difference in the outcome? We do know that hyperopic refractive surgery is associated with more regression than surgery for patients with myopia. Was this a consideration in selecting patients for LASIK? It is easier to enhance a patient who has had a LASIK flap than one who has had a PRK.
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El-Agha et al DR DAVID J. SCHANZLIN. I congratulate Dr McCulley for membrane dystrophy or problems with obtaining suction; this outstanding work and a good comparison between that wasn't the case. These were consecutive trials doing these 2 techniques. I do share some concerns about the PRK when LASIK wasn't available; when LASIK became public health issues these procedures may produce over available, consecutive LASIK patients. the coming years. Therefore I believe that it is important Dr Mazow, we do an extensive history and exam, to stratify the data into different degrees of correction. I including EOM and visual function. We certainly take a would like to ask Dr McCulley if he noticed any differ- history, and we examine the patient extensively. If there is ence in his results between those patients who had less any issue that gives us concern, in my book and in our and those who had greater than 3 diopters of hyperopia? practice, that patient becomes a non-candidate. This is a The laser times are long for those with over 3 diopters of cosmetic procedure, so if there are any issues that hyperopia; there may be more regression with time in increase risk, then those patients become noncandidates, these patients. The results, when stratified, may look and if they go down the street and find someone else to do quite different. The energy delivered to eyes with proit, then fine. I am not going to participate in doing anylonged laser times may generate a new population of thing that has increased risk to harm them. patients with cataracts. Although the energy of the laser Dr Swab, I'm not certain about the public health is absorbed at the surface, the acoustic wave that is generproblem. I think that one thing you did not mention is the ated follows the same general path as light does and there- availability of donor corneas in the future, and I am confore comes to focus close to the posterior capsule of the cerned about that as a corneal surgeon. We are going to lens. It is in my impression that patients who undergo have to be able to exclude these patients as donors. We high hyperopic correction seem to have a higher inci- certainly do an extensive dilated lens evaluation initially, dence of cataracts developing a few months following the and to respond to one of the other comments by Dr LASIK surgery. I believe we need to gather more data Schanzlin, we do dilated exams up to the year exam, to about this. Thank you. ensure that initially there are no lens changes, and we look again at a year, and have seen no suggestion of laser DR JAMES P. MCCULLEY. Thank you very much for your induced lens changes. Dave does have a philosophical comments. For me this is always the most fun part of the point of view, that we should address, and that is that the meeting, i.e., hearing the comments and critiques, and Excimer Laser procedure is a permanent procedure; then having the opportunity to respond. Dr Asbell was whereas, his insertable rings are not. I would love to have absolutely right. This was not a randomized trial. The first hyperopic inserts, and I look forward to the day when we patients were done as a part of the FDA PRK trial. have those, as they have the potential to be reversible and Otherwise, to be perfectly honest with you, we would not nonpermanent. Contributing to decreased contrast sensihave been able to recruit PRK patients; the patients would tivity with the procedure may indeed be real. The FDA have opted for the alternative of LASIK. I don't think there Ophthalmic Device Panel had its biggest concern about will be a randomized trial. I agree with you that a randomdecreased contrast sensitivity and driving in the older ized trial with masked observers is the best way to go, but population when we evaluated the multi-focal intraocular I don't think that will happen. I don't think the public lens, and indeed there are some changes that can be would accept it, and with the relative advantage of LASIK measured and they can raise some concerns about driving over PRK in hyperopia being even greater than it is in under dim conditions or in fog. Keratorefractive surgery myopia, I really doubt that it would be possible to do. could indeed have an additive effect in that patient popuRelative to meta analysis, after hearing a lot about it a lation. The intraocular pressure issue can be dealt with. few years ago and being ignorant about it at the time, I We have published a paper looking at PRK and the acculooked it up in the dictionary, and I have used it in the racy of intraocular pressure measurement. Dr Schanzlin interim. In actual fact in my view meta analysis is a statisdid a similar study in LASIK. Central Goldmann tonotical tool to apply when it is not possible to do or have metric measurements are low after either procedure. access to the ideal data, so it is a backup approach in my However, with pneumotonometry, central measurements view, not a strong primary tool. It is something we can match peripheral Goldmann measurements. So one apply when we don't have the ideal or we are not able to either needs to be aware that the Goldmann is going to accomplish the ideal. measure lower and either find peripheral uninvolved In our study, there were some issues that came up cornea on which to use the Goldmann or use pneuthat were not absolutely consistent. That's what happens motonometry. The issue about creating another public when one evaluates consecutive patients, i.e., we excludhealth problem because these patients may not come back ed no one. I can answer then the question about exclusion in for exams will not be a problem because, unfortunateof patients from LASIK to PRK because of anterior ly, they will still be presbyopic, so they will be coming back
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Excimer Laser Treatment ofof Spherical Hyperopia
in for examinations. And I think we clearly have to educate our patients that we are correcting their refractive error, (and this may be even more important with the myopes) we are not anatomically correcting their eyes; they still are at the same risk for the associated problems with myopia, with hyperopia, and with aging. And it is our responsibility to educate the patients to this fact. Dr Spaeth had a comment about the randomization. I agree with the ideal. From a practical standpoint, I don't think that is going to happen, at least with hyperopic PRK/LASIK. This trial was in hyperopia, the first where PRK and LASIK were compared, and we controlled as much as could be controlled. Randomization would be almost impossible at this time for the reasons stated above. George, I share your concern about the longer use of steroids. I am not aware of any data about 1 week of topical steroids leading to cataractogenesis, but if there are any good randomized control trials that demonstrate that, I sure would like to know about them, or even anecdotal presentations of that. The short duration of the required topical medications postop LASIK is one of the major advantages to LASIK over PRK.
I think with LASIK, there appears to be less regression than with PRK, both from our study and from the trials submitted to the FDA. Indeed it is easier to retreat after LASIK simply by lifting the flap than it is after PRK. One fact we need to keep is mind in assessing refractive stability is that roughly between the ages of late 30's and early 60's, there is a hyperopic refractive shift in the normal population. So the drift is toward hyperopia over time, unless there are significant nuclear sclerotic changes, which causes a problem in looking at stability of both myopic and hyperopic refractive procedures because the normal tendency is to drift toward hyperopia. Dr Schanzlin, I agree with you that there needs to be stratification. Just as in myopia, where the lower degrees of myopia get better results than the higher degrees of myopia, the same is true in hyperopia. Our study simply was not large enough for us to stratify. The 2 study populations were similar, so that bias would be removed, but if we were looking at +1's and +2's as opposed to +5's and +6's, there would indeed be a difference in outcome. I believe that covers all the issues raised. I really very much appreciate the opportunity to present, and I especially appreciate the comments made from the audience.
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