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Photorefractive keratectomy for pediatric anisometropia: safety and impact on refractive error, visual acuity, and stereopsis
Photorefractive Keratectomy for Pediatric Anisometropia: Safety and Impact on Refractive Error, Visual Acuity, and Stereopsis EVELYN A. PAYSSE, MD, M. BOWES HAMILL, MD, MOHAMED A.W. HUSSEIN, MD, AND DOUGLAS D. KOCH, MD
● PURPOSE: To establish the safety and possible efficacy of excimer laser photorefractive keratectomy (PRK) for treatment of pediatric anisometropia. ● DESIGN: Interventional case series ● METHODS: This is a prospective, noncomparative interventional case series at an individual university practice of photorefractive keratectomy in 11 children aged 2 and 11 years with anisometropic amblyopia who were unable or unwilling to use contact lens, glasses, and occlusion therapy to treat the amblyopia. The eye with the higher refractive error was treated with PRK using a standard adult nomogram. The refractive treatment goal was to decrease the anisometropia to 3 diopters or less. Main outcome measures were cycloplegic refraction, refractive correction, degree of corneal haze, uncorrected and best spectacle-corrected visual acuity, and stereopsis over 12 months. ● RESULTS: All patients tolerated the procedure well. The mean refractive target reduction was ⴚ10.10 ⴞ 1.39 diopters for myopia and ⴙ4.75 ⴞ 0.50 diopters for hyperopia. The mean achieved refractive error reduction at 12 months for myopia was ⴚ10.56 ⴞ 3.00 diopters and for hyperopia was ⴙ4.08 ⴞ 0.8 diopters. Corneal haze at 12 months was minimal. Uncorrected visual acuity improved by 2 or more lines in 6 (75%) of the Biosketch and/or additional material at www.ajo.com Accepted for publication Jan 14, 2004. From the Cullen Eye Institute, Baylor College of Medicine, Department of Ophthalmology, Texas Children’s Hospital, Houston, Texas (E.A.P., M.B.H., M.A.W.H., D.D.K.); and Department of Pediatrics, Baylor College of Medicine, Texas Children’s Hospital, Houston, Texas (E.A.P.). This manuscript is based on a portion of a thesis that was prepared in partial fulfillment of the requirements for membership in the American Ophthalmological Society. This study supported in part by an unrestricted grant from Research to Prevent Blindness, Inc., New York, New York. This study was presented in part at the annual meeting of the American Association for Pediatric Ophthalmology and Strabismus in Seattle, Washington, March 2002. Inquiries to Evelyn A. Paysse, MD, Baylor College of Medicine, Texas Children’s Hospital, 6621 Fannin Street, CC 640.00, Houston, Texas 77030; fax: 713-796-8110; e-mail: [email protected]
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eight children able to perform psychophysical acuity tests. Best spectacle-corrected visual acuity improved by 2 lines in 3 (38%) of patients. Stereopsis improved in 3 (33%) of nine patients. ● CONCLUSIONS: Pediatric PRK can be safely performed for anisometropia. The refractive error response in children appears to be similar to that of adults with comparable refractive errors. Visual acuity and stereopsis improved despite several children being outside the standard age of visual plasticity. Photorefractive keratectomy may play a role in the management of anisometropia in selected pediatric patients. (Am J Ophthalmol 2004;138:70 –78. © 2004 by Elsevier Inc. All rights reserved.)
E
XCIMER LASER REFRACTIVE SURGERY HAS BEEN SUC-
cessfully used for treatment of myopia, hypermetropia, and astigmatism in adults.1–3 As advances in excimer laser surgery occur, new indications for refractive surgery are expected, including its use in children. One indication currently being investigated is its use in treating children with anisometropia associated with amblyopia. Amblyopia is the most frequent cause of visual impairment in children and young adults in the United States and Western Europe.4 –7 Anisometropia is a major cause of amblyopia. Traditional treatment options for anisometropic amblyopia include refractive correction with spectacles or contact lenses and occlusion or optical and pharmacologic penalization of the sound eye. Children with severe refractive anisometropia are commonly intolerant to spectacle correction because of resultant aniseikonia and diplopia caused by refractive correction. Contact lenses, the other traditional treatment of anisometropia, are often difficult to use in children. Few studies have been published regarding the effect of photorefractive keratectomy (PRK) and laser in situ keratomileusis (LASIK) in children.8 –16 Most of these reports have been done outside the United States and have typically included children older than 6 years, an age at which treatment of amblyopia is less successful.8 –10,12–15
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0002-9394/04/$30.00 doi:10.1016/j.ajo.2004.01.044
Excimer laser refractive surgery may indeed be a viable alternative treatment option for anisometropia, if found in the long-term to be safe and effective. The purpose of this study was to evaluate the results of excimer laser PRK for anisometropia in children with anisometropic amblyopia uncooperative with the conventional treatment using spectacles or contact lenses and occlusion therapy.
PATIENTS AND METHODS THIS STUDY WAS APPROVED BY THE INSTITUTIONAL RE-
view Board of Baylor College of Medicine. Eleven patients between 2 and 11 years of age were treated with PRK for severe anisometropia. All children included in this study were treatment failures of traditional treatment for anisometropia with glasses or contact lenses and occlusion therapy. Inclusion criteria were (1) anisomyopia of at least ⫺6 diopters or anisohyperopia of at least ⫹4 diopters, (2) poor compliance with spectacles or with contact lenses for the treatment of the anisometropia, or both, and (3) amblyopia of the eye with the highest refractive error. Children with an abnormality of the cornea, lens or central retina were excluded. One child had had lasertreated retinopathy of prematurity, but the posterior pole of both eyes was normal. Photorefractive keratectomy was chosen as the refractive procedure instead of LASIK because we felt PRK had a better risk profile with less risk of the serious postoperative complications seen with LASIK such as flap dislocation, flap striae, and late keratoectasia. Preoperatively, all children underwent a comprehensive ophthalmologic examination by a pediatric ophthalmologist (EAP). Data collected from this examination for the study included stereoacuity testing using the Titmus stereo fly test, uncorrected and best spectacle-corrected visual acuity, ocular motility, biomicroscopy, and cycloplegic refraction. Visual acuity testing was done with the most sophisticated visual target possible. The younger children were tested with fixation and following response and vertical prism test for fixation preference. Titmus stereo fly test was chosen to test stereoacuity because of its ease of use and reproducibility in young children. Psychophysical visual acuity testing was done as patient cooperation permitted. Pachymetry and keratometry were performed during the preoperative examination in cooperative patients, and under general anesthesia before the procedure in uncooperative patients. The general anesthesia induction was performed in a standard fashion. All children requiring general anesthesia had their procedure performed in a children’s hospital operating room as previously reported17 and as briefly reviewed below. To minimize the risk of adverse interactions of inhalational anesthetic agents with the performance of the excimer laser procedures, induction of general anesthesia for those children needing it was carried VOL. 138, NO. 1
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out in an induction room using halothane and nitrous oxide by mask inhalation. An intravenous line was placed after the child was asleep, and a laryngeal mask airway (LMA) was inserted. An adhesive, nonporous drape was placed over the LMA to further minimize escape of the inhalational anesthetic agents. The patient was then transported to the operating room. Before entering the operating room, the halothane was discontinued. In the operating room, the LMA was connected to a standard semi-closed circle system through which the patient received 70% nitrous oxide in oxygen. Nitrous oxide given through the closed circuit was administered throughout the remainder of the case. Photorefractive keratectomy was performed as follows. The excimer laser used for all procedures was the VISX Star S2 laser. The head was first fixated in the correct position such that the plane of the iris was perpendicular to the laser beam. A lid speculum was placed in the eye to be treated, and the laser aiming beam was centered on the entrance pupil. The eye was fixated using 0.5 Castroviejo forceps with attention to avoid pressure on the globe. A fixation ring was not needed, and an eye tracking system was not used. In myopic treatment, the epithelium was removed using laser scrape to 30-m to 35-m depth, depending on the age of the patient. The optical zone size was 6.5 mm for the myopic patients. After this was completed, any residual epithelium was removed using a spatula. For hyperopic treatments, the epithelium was removed manually. The optical zone size for hyperopic correction was 9.0 mm. The refractive goal in each patient was to decrease the anisometropia to 3 diopters or less with the maximum myopic treatment of ⫺11.50 diopters. By reducing the anisometropia to less than or equal to 3 diopters, the aniseikonia would be reduced to the point where fusion was possible, and amblyopia would be more amenable to treatment with occlusion or penalization. We limited our myopic treatment to no more than ⫺11.50 diopters, even though some of our patients had much higher levels of myopia because of the considerable risk of severe corneal haze with PRK for higher levels of myopia. The maximum hyperopic treatment was for spherical equivalent of ⫹5.25 diopters. During the PRK procedure, two observers placed themselves on either side of the patient to position their eyes in line with the patient’s eyes. The treating ophthalmologist ensured that the treatment remained centered, while the two observers ensured that the patient’s iris plane remained perpendicular to the laser beam. A 6.5-mm ablation was performed for myopic PRK, and a 9-mm ablation was performed for hyperopic PRK according to the reference treatment intended. After the procedure, topical atropine 1%, ketorolac 0.5% (Acular), and gentamicin were placed in the treated eye and a disposable contact lens (SureVue) was placed on the cornea. Collagen plugs were inserted into the upper and lower puncta, and a soft FOR
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OF
Poor Poor Poor Poor Poor Poor Poor Poor Poor Poor Poor 1⫹ 0.5⫹ 0 0.5⫹ 0 2⫹ 0.5⫹ 0.5⫹ 0 0.5⫹ 1⫹
OPHTHALMOLOGY
* ⫽ Follow up for 6 months BSCVA ⫽ Best spectacle-corrected visual acuity; F&F ⫽ Fix and follow; PD ⫽ Prism diopters; SE ⫽ spherical equivalent; UCVA ⫽ Uncorrected visual acuity.
Unable 0.59 Unable 0.57 0.38 Unable Unable Unable Unable 0.40 1.05 Ortho Ortho Ortho Ortho Ortho Ortho ET 16 X(T) 14 Ortho Ortho Ortho Unable Nil Unable 140 50 Nil Nil Nil Nil 400 60 F&F 20/100 20/50 20/100 20/25 20/100 20/1000 20/80 2/200 20/40 20/30 F&F 20/200 20/50 20/100 20/25 20/100 20/1000 20/100 2/200 20/40 20/50 ⫺5.00 D ⫺0.50 ⫺0.50 D ⫺7.00 D ⫹0.50 D ⫺4.75 D ⫺4.75 D ⫺1.75 D ⫺1.00 D 0.25 D 1.25 D ⫺11.5 D ⫺10.00 D ⫺10.00 D ⫺10.00 D ⫹4.25 D ⫺11.50 D ⫺10.00 D ⫺7.00 D ⫺10.50 D ⫹5.25 D ⫹4.75 D Ortho Ortho Ortho Ortho Ortho Ortho ET 25 ET 20 Ortho Ortho Ortho F&F 20/300 F&F 3/400 20/60 20/200 20/1000 20/250 5/400 20/300 20/200 3 8 2 6 10 4 7 4 4 11 8 1 2 3 4* 5 6 7 8 9 10 11
⫺15.75 D ⫺10.00 D ⫺13.75 D ⫺15.75 D ⫹4.25 D ⫺11.50 D ⫺21.00 D ⫺9.75 D ⫺11.75 D ⫹5.25 D ⫹4.75 D
BSCVA
Unable Nil Unable Nil 800 Nil Nil Nil Nil 400 400
Ocular Alignment (PD) UCVA
F&F 20/200 F&F 20/200 20/30 20/200 20/1000 20/200 5/400 20/40 20/50
Refraction (SE)
UCVA
BSCVA
Stereoacuity (Sec of Arc)
1-year Postoperative Data
Stereoacuity (Sec of Arc) Pt #
are shown for each patient in Table 1. The mean age of the children was 6.8 years (2–11 years). Nine children (82%) were male, and 10 of the treated eyes (91%) were right eyes. Eight children were treated for anisomyopia, and 3 for anisohyperopia. Nine children (82%) required general anesthesia. Ten (91%) of 11 patients were followed up at 12 months. Mean follow-up time was 11.9 months (6 – 12 months) (Table 2). No anesthetic complications occurred. All patients were discharged promptly, usually within 1 hour of the procedure.
Refraction (SE)
INDIVIDUAL PREOPERATIVE AND POSTOPERATIVE DATA
Age (Yrs)
RESULTS
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Intended Refractive Treatment (SE) Preoperative Data
TABLE 1. Preoperative and Postoperative Results of All Treated Patients
Ocular Alignment (PD)
Corneal Centration (mm)
Haze (0–4⫹)
Amblyopia Therapy Compliance
patch was placed over the eye until the patient was awake and coherent. The postoperative medical regimen included topical ofloxacin (Ocuflox) and loteprednol 0.5% (Lotemax) four times a day until the corneal epithelium healed. Topical ketorolac was prescribed up to four times a day as needed for moderate discomfort for the first 2 postoperative days. Hydrocodone oral elixir (Lortab) was available as needed for severe discomfort in the first week. Loteprednol was changed to fluorometholone 0.25% (FML forte) after 1 week. Patients used the fluorometholone four times a day for 1 month and then underwent a slow taper over the next 5 months. Patients were examined daily until corneal epithelial healing was complete, which occurred by 3 days in the myopic group and by 5 days in the hyperopic group.18 The contact lens was then removed. The patients were examined 1 month after the procedure and then every 3 months for 12 months. Refractive correction was prescribed as needed at the 1-month examination. Occlusion therapy was recommended up to 8 hours per day for the sound eye based on the child’s age and visual deficit. Compliance was assessed at each follow-up visit by asking the parent directly using a compliance scale developed by the Pediatric Eye Investigator Group for the Amblyopia Treatment Study.7 Data collected at each follow-up examination included stereoacuity, uncorrected and best spectaclecorrected visual acuity, ocular motility, degree of corneal haze, and cycloplegic refraction. Postoperative subepithelial corneal haze was graded on a scale of 0 to 4⫹ (0 ⫽ clear cornea; 1⫹ ⫽ trace haze, only detectable with tangential illumination, 2⫹ ⫽ mild, discrete haze visible with difficulty by focal illumination, 3⫹ ⫽ moderately dense opacity partially obscuring iris detail; 4⫹ ⫽ dense opacity obscuring details of intraocular structures). Postoperative corneal topography was performed as patient cooperation allowed at the 12-month visit. Centration was determined using tangential maps from the Humphery Atlas according to the method described by Lin and coauthors.19
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TABLE 2. Patient Characteristics/Refractive Results
Number of patients General anesthesia Mean age in years (range) Mean preoperative K readings ⫾ SD Mean preop corneal thickness ⫾ SD Mean preoperative SE ⫾ SD Maximum refractive SE treatment Mean target SE ⫾ SD Mean 12-month postoperative SE ⫾ SD Mean 12-month target SE reduction ⫾ SD Mean 12-month SE reduction ⫾ SD Mean SE regression ⫾ SD % within 1 D of target at 12 months % within 2 D of target at 12 months % reduction in refractive error
Myopia Group
Hyperopia Group
8 8 4 (3–8) 44.80 D ⫾ 1.54 D 521 ⫾ 43.4 ⫺13.7 ⫾ 3.77 D ⫺11.50 D ⫺3.5 ⫾ 3.75 D ⫺3.3 ⫾ 2.5 D 10.10 D ⫾ 1.39 D 10.56 ⫾ 3.00 D 2.50 ⫾ 2.23 D 50% 63% 76%
3 1 9 (8–12) 42.30 D ⫾ 1.06 D 536 ⫾ 4.24 ⫹4.75 ⫾ 0.50 D ⫹5.25 D plano ⫹1.00 ⫾ 0.5 D 4.75 D ⫾ 0.5 D 4.08 ⫾ 0.8 D 1.10 ⫾ 1.6 D 67% 100% 79%
K ⫽ keratometry; SD ⫽ standard deviation; SE ⫽ spherical equivalent.
● REFRACTIVE ERROR RESULTS-MYOPIA GROUP:
Table 2 shows demographics and complete refractive results. The mean preoperative spherical equivalent in the myopic group was ⫺13.70 ⫾ 3.77 diopters. The mean final target spherical equivalent was ⫺3.50 ⫾ 3.75 diopters. The mean 12-month postoperative myopic spherical equivalent was ⫺3.30 ⫾ 2.50 diopters. The mean target refractive error reduction was 10.10 ⫾ 1.39 diopters of myopia. The mean refractive error reduction at 12 months was 10.56 ⫾ 3.00 diopters of myopia (Table 2, Figure 1A). The mean spherical equivalent difference between the 12-month target and 12-month achieved refractive change after myopic PRK was 0.18 ⫾ 3.5 diopters of overresponse. No patient had an over-response that created hyperopia. Four myopic individuals (50%) were within 1 diopter of target refractive spherical equivalent and five (63%) were within 2 diopters (Figure 1A). There were two patients who were highly myopic preoperatively who achieved a greater degree of correction than targeted. One patient (patient 7) with a preoperative spherical equivalent refractive error of ⫺21.00 diopters had a refractive target reduction of 11.50 diopters and ended up with the final refractive reduction of 16.75 diopters and a 12-month spherical equivalent result of ⫺4.75 diopters. The other (patient 3), with a preoperative spherical equivalent refractive error of ⫺13.75 diopters had a refractive target reduction of 10.50 diopters and at 12 months ended up with the final refractive reduction of 13.25 diopters and a final spherical equivalent result of ⫺0.50 diopters. Refractive error stability over the follow-up period is outlined in Figure 2A. Our myopic group had mild to moderate refractive regression over the 12-month folVOL. 138, NO. 1
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low-up period, with a mean spherical equivalent regression of 2.50 ⫾ 2.23 diopters over the 12-month follow-up. ● REFRACTIVE ERROR RESULTS–HYPEROPIA GROUP:
The mean preoperative spherical equivalent in the hyperopic group was ⫹4.75 ⫾ 0.5 D. The mean final target spherical equivalent in this group was plano. The mean 12-month postoperative hyperopic spherical equivalent was ⫹1.00 ⫾ 0.5 diopter. The mean target refractive error reduction was 4.75 ⫾ 0.5 diopters. The mean refractive error reduction at 12 months was ⫹4.08 ⫾ 0.8 D diopters (Table 2, Figure 1B). The mean spherical equivalent difference between the 12-month target and 12-month achieved refractive change after hyperopic PRK was 0.96 diopters of under-response. Two hyperopes (67%) were within 1 diopter of target spherical equivalent, and all were within 2 diopters (Figure 1B). Refractive error stability over the follow-up period is outlined in Figure 2B. Our hyperopic group showed mild refractive regression as well with a mean spherical equivalent regression of 1.10 ⫾ 1.60 diopters over the 12-month follow-up interval. ● CORNEAL HAZE AND TOPOGRAPHY:
The mean corneal haze measurement 12 months after surgery was 0.50⫹ (0 to 2⫹) (Figure 3). All but one child with residual corneal haze were myopic. Only one patient had mild to moderate corneal haze (2⫹). This child had not been compliant with the postoperative treatment protocol. He did not return for follow-up after the 1-month examination until the 12-month examination and discontinued the fluorometholone drops 1 month after the
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FIGURE 2. (A) Refractive error stability over time (myopic subgroup). (B) Refractive error stability over time (hyperopic subgroup) SE ⴝ spherical equivalent.
FIGURE 1. (A) Refractive treatment goal compared with the 12-month results (myopic children). Note that the points above the line represent over-response from target and those below the line represent under-response from target. (B) Refractive treatment goal compared with the 12-month results (hyperopic children). Note that the points above the line represent overresponse from target and those below the line represent underresponse from target.
surgery. The remainder of the patients had only minimal or no haze. Corneal topography was performed on five patients, and the amounts of decentration are shown in Table 1. The full results have been published elsewhere.16 The mean decentration was 0.60 ⫾ 0.27 mm.
FIGURE 3. Corneal haze at 1 month and 12 month postoperatively. Patients without a bar in the graph at either visit had no haze at that visit.
● VISUAL ACUITY:
In the eight patients able to perform psychophysical acuity tests preoperatively and postoperatively, uncorrected visual acuity improved by 2 or more lines in six eyes (75%) with the maximum improvement of seven lines (Figure 4A and Table 3). In this same group, best spectacle-corrected visual acuity improved at 12 months by 2 or more lines in three eyes (38%) and remained within 1 line of the preoperative visual acuity in four eyes (50%). One patient with a preoperative logarithm of the minimal angle of resolution visual acuity of 1 (20/200) lost acuity to the level of logarithm of the minimal angle of resolution 1.3 (20/400). This is the child who discontinued the topical corticosteroids postopera-
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tively at 1 month and had the highest level of corneal haze at 12 months (Figure 4B). ● STEREOACUITY, OCULAR ALIGNMENT, AND AMBLYOPIA THERAPY COMPLIANCE: Stereopsis was testable in nine
children. Six had no measurable stereoacuity before or 12 months after the treatment using the Titmus fly test. Three patients realized an improvement in stereopsis. One improved from 800 seconds to 50 seconds of arc stereo, another improved from 400 seconds to 60 seconds of arc stereo, and the last patient improved from no measurable stereopsis to 140 seconds of arc stereo. Ocular alignment did not change OF
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TABLE 3. logMAR Equivalents Snellen
logMAR Equivalents
20/20 20/30 20/40 20/50 20/60 20/80 20/100 20/200 20/600 20/2000
0.0 0.2 0.3 0.4 0.5 0.6 0.7 1.0 1.5 2.0
logMAR ⫽ logarithm of the minimal angle of resolution.
FIGURE 4. (A) Comparison of preoperative and 12-month postoperative uncorrected (logMAR) visual acuity. As examples on the logMAR scale, 20/20 is equivalent to 0, and 20/200 is equivalent to 1.0. The closer the value is to zero, the better the visual acuity. Points below the line represent improved postoperative visual acuity and points above the line represent reduced postoperative visual acuity. (B) Comparison of preoperative and 12-month postoperative best spectacle-corrected logMAR visual acuity. Points below the line represent improved postoperative visual acuity, and points above the line represent reduced postoperative visual acuity.
postoperatively in any patient. Compliance with amblyopia occlusion therapy did not improve postoperatively.
DISCUSSION ANISOMETROPIA IS A MAJOR CAUSE OF AMBLYOPIA.4 –7
Compliance with treatment is often poor because the sound eye usually sees well without refractive correction. Refractive surgery in children may be a viable treatment option for children with significant anisometropia, especially when compliance issues arise. VOL. 138, NO. 1
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Both LASIK and PRK have been shown in several studies to be safe in children.8 –10,12–14,16 Most published studies have been done outside the United States and have predominantly included children aged 7 years and older.8 –10,12–14,16 Only one published report to date has included a number of children younger than 7 years of age.13 By 7 to 8 years of age, amblyopia is less likely to respond to therapy, because the period of visual cortical plasticity has passed. Ideally, amblyopia should be treated as early in life as possible. If refractive surgery is to play an active role in treatment of anisometropic amblyopia, it is likely that it too will need to be applied early in life. Our pilot study included 11 patients aged 2 to 11 years, with roughly 50% under 6 years of age. These are some of the youngest children reported to date that have undergone a refractive procedure. We chose to perform PRK instead of LASIK in our pilot study, because we felt it was the safer of the two procedures. We understand that potential advantages of LASIK over PRK in adults have been reported, such as faster recovery of vision, less discomfort, maintenance of an intact Bowman membrane, and, possibly, a more predictable outcome with higher levels of myopia.8 Laser in situ keratomileusis, however, has more serious potential longterm complications, such as corneal flap dislocation, flap striae, and late keratoectasia. After evaluating the risks and benefits of each procedure, we selected PRK as the refractive procedure for our children. The refractive goal in our study was to reduce the amount of anisometropia to less than or equal to 3 diopters. The aniseikonia would then be reduced to the point where fusion was possible and amblyopia may be more amenable to occlusion therapy. We chose not to treat the full amount of myopia in our patients with greater than ⫺11.50 diopters of spherical equivalent myopia, because PRK for these higher levels of myopia has been associated with significant corneal haze in adults. Interestingly and beneficially, two patients with extremely high FOR
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levels of myopia (spherical equivalent of ⫺21.00 diopters and ⫺13.75 diopters) had larger than expected responses to the PRK dose, bringing their final refractive errors to ⫺4.75 diopters and ⫺0.50 diopters, respectively. Both were within 3 diopters of each child’s fellow eye. Why this over-response occurred in our extremely high myopic individuals is not known. Williams noted this same result in adults with refractive errors greater than ⫺10.00 diopters.20 Astle and associates13 also noted this same result in his series of highly myopic children treated with PRK. Reduced scleral rigidity and a difference in corneal remodeling in the highly myopic eye may play a role in both adults and children with extremely high levels of myopia. With further study, if this outcome is found to be consistent in extremely high myopia, modification of the treatment nomograms would be indicated. In our myopic subgroup, 50% of the patients were within 1 diopter of the refractive target and 63% were within 2 diopters. The mean preoperative refractive error of ⫺13.70 diopters was reduced to a mean postoperative refractive error of ⫺3.30 diopters. These results are in agreement with those found in previous studies of PRK in myopic children, though our cohort included younger children than most.11–14 They also are in line with results reported from adults with similar levels of extremely high myopia treated with PRK.21–22 In our hyperopic group, 67% of the patients were within 1 diopter of the refractive target and all were within 2 diopters. The mean preoperative refractive error of ⫹4.75 diopters was reduced to a mean postoperative refractive error of ⫹1.00 diopter. These results are also is in agreement with the data from the only other published study that included pediatric hyperopic PRK.12 Our myopic group had moderate refractive regression over the 12-month follow-up period with a mean spherical equivalent regression of 2.50 diopters over the 12-month follow-up (Figure 2A). This result is in line with the refractive regression seen in high myopic adults treated with PRK.23–25 Other studies in children treated with PRK for myopia have shown a myopic shift (i.e, regression) ranging from 0.8 diopters to 1.7 diopters over a 1-year period.11,14 Our hyperopic group showed mild refractive regression as well with a mean spherical equivalent regression of 1.10 diopters over the 12-month follow-up interval. This regression again is in line with that found in adult hyperopic PRK.26 Four (36%) of our study patients had a minimal degree of residual corneal haze, and one child had mild to moderate corneal haze 1 year after surgery. All but one of these children were high myopic individuals. The child in our study with the mild to moderate haze (patient 5) was the patient who was noncompliant with the postoperative topical corticosteroid regimen. High degrees of corneal haze have also been reported in adults with high myopia treated with PRK.23 Only the child with the mild to moderate corneal haze lost 1 line of best spectacle-corrected visual acuity. All others (88%) had stable or improved visual acuity. 76
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Alio reported that corneal haze was the main optical complication after pediatric PRK but that it decreased by 1 year.11 Approximately 30% of children treated with PRK in Alio’s study had mild corneal haze 1 year after surgery; 80% were high myopic patients. In the only study that included hyperopic PRK in children, corneal haze was not a problem.12 Corneal haze in children treated with PRK has been reported to diminish considerably after 1 year.11 Our patients fortunately did not experience significant corneal haze. Our low incidence of corneal haze may be attributable to the longer use of topical corticosteroids, or it could be attributable to improvements in excimer laser technology. In our cohort, we used the VISX Star S2 laser, a third-generation excimer laser. Older studies used first-generation broad-beam excimer lasers.11–12 Most patients enjoyed improved uncorrected visual acuity and best spectacle-corrected visual acuity. Only one patient lost best corrected visual acuity; all others either improved or maintained their acuity. We felt the loss in acuity in this patient was because of corneal haze resulting from noncompliance with the postoperative topical corticosteroid regimen. Our acuity results are in accordance with the published results in adult patients treated with PRK.24,26 –27 Conversely, our result are somewhat surprising because most of the children had profound long-standing amblyopia and 45% of them were 7 years old or older, typically beyond the sensitive period of visual development. We feel that if refractive surgery were performed at an earlier age, before severe amblyopia has occurred, long-term visual outcomes would probably be markedly better. As an example, our youngest patient, who preoperatively at age 2 years could only be visually tested preoperatively with fix and follow testing, had a bestcorrected visual acuity of 20/40 at the 12 months’ postoperative visit despite his continued lack of compliance with spectacle use and amblyopia therapy. Based on our experience with other patients with similar levels of anisometropia and poor compliance, his visual acuity would most likely have been significantly worse in this eye if refractive surgery had not been done. Stereoacuity improved in one third of our testable cohort. This was an unexpected and encouraging finding, as most of our patients were well beyond 2 years of age, the age at which most ophthalmologists feel stereopsis development is complete. All children in our study who required general anesthesia had their procedure in an operating room at our children’s hospital without an adverse complication.17 As long as the idiosyncrasies of the excimer laser are addressed, excimer laser procedures can be performed accurately, safely, and efficiently under general anesthesia. The 193-nm wavelength of the argon fluoride excimer laser lies within the absorption spectrum of many anesthetic gases, including nitrous oxide. If a volatile gas escapes, attenuation of the laser beam occurs and the laser increases voltage in an effort to maintain fluence until the laser stops firing and an error message appears. OF
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Because of these issues, we used an LMA and a specific induction procedure outside of the operating room and had no problems with the functioning of our laser. Centration is another potential problem with excimer laser procedures performed under general anesthesia. Centration in our study patients was adequate. Our centration results are within the acceptable range, achieved in most by using observers on either side of the eye to ensure that the iris plane was maintained perpendicular to the laser beam.17 The one exception was one hyperopic patient with a decentration of 1.05 mm. This child’s postoperative uncorrected visual acuity was 20/50 and her best spectaclecorrected visual acuity was 20/30 in this eye. Fixation devices such as the Arrowsmith fixation ring were considered but not used, because we found our protocol with the two observers to be reliable. Perhaps a fixation ring could better ensure centration when performing the larger hyperopic ablations, however, there were too few patients in this study to draw any definite conclusions. The VISX Star S2 laser we used did not have an eye tracking system. An eye tracking system would probably not be that useful under general anesthesia, as it only ensures centration on the pupil and does not guard against an oblique contact of the laser beam on the cornea. The observers ensured this perpendicular entry in our study patients. Our procedure, though effective, was cumbersome and labor intensive. If refractive procedures become more commonly performed under general anesthesia, a device that maintains the laser beam normal to the anterior corneal surface may be of use. In summary, our 12-month results demonstrate that PRK appears to be safe for the treatment of anisometropia in children. The refractive error response in children appears to be similar to that of adults with comparable refractive errors; therefore, nomogram modification may not be necessary. Consideration of the expected immediate over-response in patients with extreme degrees of refractive errors, however, might be needed. More experience is needed with larger patient numbers to be able to adequately address this question, especially in terms of the patients with profound myopia. Most importantly, PRK for anisometropic amblyopia can result in improved uncorrected visual acuity, best spectacle-corrected visual acuity, and stereopsis, even in older children who are typically thought to be visually mature. Long-term follow-up for all of these issues is indicated before PRK and other refractive procedures can be recommended for general use in the pediatric population. If long-term safety can be demonstrated, then PRK may play an important role in earlier treatment of anisometropia before severe amblyopia has developed.
REFERENCES 1. Kim JH, Hahn TW, Lee YC, Joo CK, Sah WJ. Photorefractive keratectomy in 202 myopic eyes: one year results. Refract Corneal Surg 1993;9(2 suppl):S11–S16.
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2. Nagy ZZ, Krueger RR, Suveges I. Photorefractive keratectomy for astigmatism with the Meditec MEL 60 laser. J Refract Surg 2001;17:441–453. 3. Griffith M, Jackson WB, Lafontaine MD, Mintsioulis G, Agapitos P, Hodge W. Evaluation of current techniques of corneal epithelial removal in hyperopic photorefractive keratectomy. J Cataract Refract Surg 1998;24:1070 –1078. 4. Greenwald MS, Parks M. Amblyopia: In: Tasman W, Jaeger EA, editors: Duane’s clinical ophthalmology. Chapter 10. Philadelphia: JB Lippincott, 1994:1. 5. Mittelman D. Amblyopia. Pediatr Clin North Am 2003;50: 189 –196. 6. LaRoche GR. Amblyopia: detection, prevention, and rehabilitation. Cur Opin Ophthalmol 2001;12:363–367. 7. Repka MX, Beck RW, Holmes JM, Birch EE, Chandler DL, Cotter SA, Hertle RW, Kraker RT, Moke PS, Quinn GE, Scheiman MM, Pediatric Eye Disease Investigator Group. A randomized trial of patching regimens for treatment of moderate amblyopia in children. Arch Ophthalmol 2003;121:603–611. 8. Rashad KM. Laser assisted in situ keratomileusis for myopic anisometropia in children. J Refract Surg 1999;15:429 –435. 9. Agarwal A, Agarwal A, Agarwal T, et al. Results of pediatric laser in situ keratomileusis. J Cataract Refract Surg 2000;26: 684 –689. 10. Nucci P, Drack AV. Refractive surgery for unilateral high myopia in children. J AAPOS 2001;5:348 –351. 11. Alio JL, Artola A, Claramonte P, Ayala MJ, Chinpont E. Photorefractive keratectomy for pediatric myopic anisometropia. J Cataract Refract Surg 1998;24:327–330. 12. Singh D. Photorefractive keratectomy in pediatric patients. J Cataract Refract Surg 1995;21:630 –632. 13. Astle WF, Huang PT, Ells AL, Cox RG, Deschenes MC, Vibert HM. Photorefractive keratectomy in children. J Cataract Refract Surg 2002;28:932–941. 14. Nano HD, Muzzin S, Irigary LF. Excimer laser photorefractive keratectomy in pediatric patients. J Cataract Refract Surg 1997;23:736 –739. 15. Rybintseva LV, Sheludchenko VM. Effectiveness of laser in situ keratomileusis with Nidek EC-5000 excimer laser for pediatric correction of spherical anisometropia. J Refract Surg 2001;17(suppl):S224 –S228. 16. Autrata R, Rehurek J. Clinical results of excimer laser photorefractive keratectomy for high myopic anisometropia in children: four-year follow-up. J Cataract Refract Surg 2003;29:694 –702. 17. Paysse EA, Hussein MAW, Koch DD, Wang L, Brady McCreery KM, Glass NL, Hamill MB. Successful Implementation of a Protocol for Photorefractive Keratectomy in Children requiring General Anesthesia. J Cataract Refract Surg 2003;29(9):1744 –1747. 18. Paysse EA, Hamill MB, Koch DD, Hussein MAW, Brady McCreery K, Coats DK. Epithelial Healing and Ocular Discomfort Following Photorefractive Keratectomy in Children. J Cataract Refract Surg 2003;29:478 –481. 19. Lin DT, Sutton HF, Berman M. Corneal topography following excimer photorefractive keratectomy for myopia. J Cataract Refract Surg 1993;19(suppl):149 –154. 20. Williams DK. Multizone photorefractive keratectomy for high and very high myopia: long-term results. J Cataract Refract Surg 1997;23:1034 –1041. 21. Shah S, Chatterjee A, Smith RJ. Predictability of spherical photorefractive keratectomy for myopia. Ophthalmology 1998;105:2178 –2184. 22. Heitzmann J, Binder PS, Kassar BS, Nordan LT. The FOR
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Summit PRK Study Group. Results of phase III excimer laser photorefractive keratectomy for myopia. Ophthalmology 1997;104:1535–1553. 26. Jackson WB, Casson E, Hodge WG, Mintsioulis G, Agapitos PJ. Laser vision correction for low hyperopia. An 18-month assessment of safety and efficacy. Ophthalmology 1998;105: 1727–1738. 27. Maguen E, Salz JJ, Nesburn AB, et al. Results of excimer laser photorefractive keratectomy for the correction of myopia. Ophthalmology 1994;101:1548 –1556.
correction of high myopia using the excimer laser. Arch Ophthalmol 1993;111:1627–1634. 23. Tabbara KF, El-Sheikh HF, Sharara NA, Aabed B. Corneal haze among blue eyes and brown eyes after photorefractive keratectomy. Ophthalmology 1999;106:2210 –2215. 24. Kim JH, Kim MS, Hahn TW, Lee YC, Sah WJ, Park CK. Five years results of photorefractive keratectomy for myopia. J Cataract Refract Surg 1997;23:731–735. 25. Hersh PS, Stulting RD, Steinert RF, Waring GO 3rd, Thompson KP, O’Connell M, Doney K, Schein OD, The
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● PURPOSE: To establish the safety and possible efficacy of excimer laser photorefractive keratectomy (PRK) for treatment of pediatric anisometropia. ● DESIGN: Interventional case series ● METHODS: This is a prospective, noncomparative interventional case series at an individual university practice of photorefractive keratectomy in 11 children aged 2 and 11 years with anisometropic amblyopia who were unable or unwilling to use contact lens, glasses, and occlusion therapy to treat the amblyopia. The eye with the higher refractive error was treated with PRK using a standard adult nomogram. The refractive treatment goal was to decrease the anisometropia to 3 diopters or less. Main outcome measures were cycloplegic refraction, refractive correction, degree of corneal haze, uncorrected and best spectacle-corrected visual acuity, and stereopsis over 12 months. ● RESULTS: All patients tolerated the procedure well. The mean refractive target reduction was ⴚ10.10 ⴞ 1.39 diopters for myopia and ⴙ4.75 ⴞ 0.50 diopters for hyperopia. The mean achieved refractive error reduction at 12 months for myopia was ⴚ10.56 ⴞ 3.00 diopters and for hyperopia was ⴙ4.08 ⴞ 0.8 diopters. Corneal haze at 12 months was minimal. Uncorrected visual acuity improved by 2 or more lines in 6 (75%) of the Biosketch and/or additional material at www.ajo.com Accepted for publication Jan 14, 2004. From the Cullen Eye Institute, Baylor College of Medicine, Department of Ophthalmology, Texas Children’s Hospital, Houston, Texas (E.A.P., M.B.H., M.A.W.H., D.D.K.); and Department of Pediatrics, Baylor College of Medicine, Texas Children’s Hospital, Houston, Texas (E.A.P.). This manuscript is based on a portion of a thesis that was prepared in partial fulfillment of the requirements for membership in the American Ophthalmological Society. This study supported in part by an unrestricted grant from Research to Prevent Blindness, Inc., New York, New York. This study was presented in part at the annual meeting of the American Association for Pediatric Ophthalmology and Strabismus in Seattle, Washington, March 2002. Inquiries to Evelyn A. Paysse, MD, Baylor College of Medicine, Texas Children’s Hospital, 6621 Fannin Street, CC 640.00, Houston, Texas 77030; fax: 713-796-8110; e-mail: [email protected]
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eight children able to perform psychophysical acuity tests. Best spectacle-corrected visual acuity improved by 2 lines in 3 (38%) of patients. Stereopsis improved in 3 (33%) of nine patients. ● CONCLUSIONS: Pediatric PRK can be safely performed for anisometropia. The refractive error response in children appears to be similar to that of adults with comparable refractive errors. Visual acuity and stereopsis improved despite several children being outside the standard age of visual plasticity. Photorefractive keratectomy may play a role in the management of anisometropia in selected pediatric patients. (Am J Ophthalmol 2004;138:70 –78. © 2004 by Elsevier Inc. All rights reserved.)
E
XCIMER LASER REFRACTIVE SURGERY HAS BEEN SUC-
cessfully used for treatment of myopia, hypermetropia, and astigmatism in adults.1–3 As advances in excimer laser surgery occur, new indications for refractive surgery are expected, including its use in children. One indication currently being investigated is its use in treating children with anisometropia associated with amblyopia. Amblyopia is the most frequent cause of visual impairment in children and young adults in the United States and Western Europe.4 –7 Anisometropia is a major cause of amblyopia. Traditional treatment options for anisometropic amblyopia include refractive correction with spectacles or contact lenses and occlusion or optical and pharmacologic penalization of the sound eye. Children with severe refractive anisometropia are commonly intolerant to spectacle correction because of resultant aniseikonia and diplopia caused by refractive correction. Contact lenses, the other traditional treatment of anisometropia, are often difficult to use in children. Few studies have been published regarding the effect of photorefractive keratectomy (PRK) and laser in situ keratomileusis (LASIK) in children.8 –16 Most of these reports have been done outside the United States and have typically included children older than 6 years, an age at which treatment of amblyopia is less successful.8 –10,12–15
ELSEVIER INC. ALL
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0002-9394/04/$30.00 doi:10.1016/j.ajo.2004.01.044
Excimer laser refractive surgery may indeed be a viable alternative treatment option for anisometropia, if found in the long-term to be safe and effective. The purpose of this study was to evaluate the results of excimer laser PRK for anisometropia in children with anisometropic amblyopia uncooperative with the conventional treatment using spectacles or contact lenses and occlusion therapy.
PATIENTS AND METHODS THIS STUDY WAS APPROVED BY THE INSTITUTIONAL RE-
view Board of Baylor College of Medicine. Eleven patients between 2 and 11 years of age were treated with PRK for severe anisometropia. All children included in this study were treatment failures of traditional treatment for anisometropia with glasses or contact lenses and occlusion therapy. Inclusion criteria were (1) anisomyopia of at least ⫺6 diopters or anisohyperopia of at least ⫹4 diopters, (2) poor compliance with spectacles or with contact lenses for the treatment of the anisometropia, or both, and (3) amblyopia of the eye with the highest refractive error. Children with an abnormality of the cornea, lens or central retina were excluded. One child had had lasertreated retinopathy of prematurity, but the posterior pole of both eyes was normal. Photorefractive keratectomy was chosen as the refractive procedure instead of LASIK because we felt PRK had a better risk profile with less risk of the serious postoperative complications seen with LASIK such as flap dislocation, flap striae, and late keratoectasia. Preoperatively, all children underwent a comprehensive ophthalmologic examination by a pediatric ophthalmologist (EAP). Data collected from this examination for the study included stereoacuity testing using the Titmus stereo fly test, uncorrected and best spectacle-corrected visual acuity, ocular motility, biomicroscopy, and cycloplegic refraction. Visual acuity testing was done with the most sophisticated visual target possible. The younger children were tested with fixation and following response and vertical prism test for fixation preference. Titmus stereo fly test was chosen to test stereoacuity because of its ease of use and reproducibility in young children. Psychophysical visual acuity testing was done as patient cooperation permitted. Pachymetry and keratometry were performed during the preoperative examination in cooperative patients, and under general anesthesia before the procedure in uncooperative patients. The general anesthesia induction was performed in a standard fashion. All children requiring general anesthesia had their procedure performed in a children’s hospital operating room as previously reported17 and as briefly reviewed below. To minimize the risk of adverse interactions of inhalational anesthetic agents with the performance of the excimer laser procedures, induction of general anesthesia for those children needing it was carried VOL. 138, NO. 1
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out in an induction room using halothane and nitrous oxide by mask inhalation. An intravenous line was placed after the child was asleep, and a laryngeal mask airway (LMA) was inserted. An adhesive, nonporous drape was placed over the LMA to further minimize escape of the inhalational anesthetic agents. The patient was then transported to the operating room. Before entering the operating room, the halothane was discontinued. In the operating room, the LMA was connected to a standard semi-closed circle system through which the patient received 70% nitrous oxide in oxygen. Nitrous oxide given through the closed circuit was administered throughout the remainder of the case. Photorefractive keratectomy was performed as follows. The excimer laser used for all procedures was the VISX Star S2 laser. The head was first fixated in the correct position such that the plane of the iris was perpendicular to the laser beam. A lid speculum was placed in the eye to be treated, and the laser aiming beam was centered on the entrance pupil. The eye was fixated using 0.5 Castroviejo forceps with attention to avoid pressure on the globe. A fixation ring was not needed, and an eye tracking system was not used. In myopic treatment, the epithelium was removed using laser scrape to 30-m to 35-m depth, depending on the age of the patient. The optical zone size was 6.5 mm for the myopic patients. After this was completed, any residual epithelium was removed using a spatula. For hyperopic treatments, the epithelium was removed manually. The optical zone size for hyperopic correction was 9.0 mm. The refractive goal in each patient was to decrease the anisometropia to 3 diopters or less with the maximum myopic treatment of ⫺11.50 diopters. By reducing the anisometropia to less than or equal to 3 diopters, the aniseikonia would be reduced to the point where fusion was possible, and amblyopia would be more amenable to treatment with occlusion or penalization. We limited our myopic treatment to no more than ⫺11.50 diopters, even though some of our patients had much higher levels of myopia because of the considerable risk of severe corneal haze with PRK for higher levels of myopia. The maximum hyperopic treatment was for spherical equivalent of ⫹5.25 diopters. During the PRK procedure, two observers placed themselves on either side of the patient to position their eyes in line with the patient’s eyes. The treating ophthalmologist ensured that the treatment remained centered, while the two observers ensured that the patient’s iris plane remained perpendicular to the laser beam. A 6.5-mm ablation was performed for myopic PRK, and a 9-mm ablation was performed for hyperopic PRK according to the reference treatment intended. After the procedure, topical atropine 1%, ketorolac 0.5% (Acular), and gentamicin were placed in the treated eye and a disposable contact lens (SureVue) was placed on the cornea. Collagen plugs were inserted into the upper and lower puncta, and a soft FOR
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Poor Poor Poor Poor Poor Poor Poor Poor Poor Poor Poor 1⫹ 0.5⫹ 0 0.5⫹ 0 2⫹ 0.5⫹ 0.5⫹ 0 0.5⫹ 1⫹
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* ⫽ Follow up for 6 months BSCVA ⫽ Best spectacle-corrected visual acuity; F&F ⫽ Fix and follow; PD ⫽ Prism diopters; SE ⫽ spherical equivalent; UCVA ⫽ Uncorrected visual acuity.
Unable 0.59 Unable 0.57 0.38 Unable Unable Unable Unable 0.40 1.05 Ortho Ortho Ortho Ortho Ortho Ortho ET 16 X(T) 14 Ortho Ortho Ortho Unable Nil Unable 140 50 Nil Nil Nil Nil 400 60 F&F 20/100 20/50 20/100 20/25 20/100 20/1000 20/80 2/200 20/40 20/30 F&F 20/200 20/50 20/100 20/25 20/100 20/1000 20/100 2/200 20/40 20/50 ⫺5.00 D ⫺0.50 ⫺0.50 D ⫺7.00 D ⫹0.50 D ⫺4.75 D ⫺4.75 D ⫺1.75 D ⫺1.00 D 0.25 D 1.25 D ⫺11.5 D ⫺10.00 D ⫺10.00 D ⫺10.00 D ⫹4.25 D ⫺11.50 D ⫺10.00 D ⫺7.00 D ⫺10.50 D ⫹5.25 D ⫹4.75 D Ortho Ortho Ortho Ortho Ortho Ortho ET 25 ET 20 Ortho Ortho Ortho F&F 20/300 F&F 3/400 20/60 20/200 20/1000 20/250 5/400 20/300 20/200 3 8 2 6 10 4 7 4 4 11 8 1 2 3 4* 5 6 7 8 9 10 11
⫺15.75 D ⫺10.00 D ⫺13.75 D ⫺15.75 D ⫹4.25 D ⫺11.50 D ⫺21.00 D ⫺9.75 D ⫺11.75 D ⫹5.25 D ⫹4.75 D
BSCVA
Unable Nil Unable Nil 800 Nil Nil Nil Nil 400 400
Ocular Alignment (PD) UCVA
F&F 20/200 F&F 20/200 20/30 20/200 20/1000 20/200 5/400 20/40 20/50
Refraction (SE)
UCVA
BSCVA
Stereoacuity (Sec of Arc)
1-year Postoperative Data
Stereoacuity (Sec of Arc) Pt #
are shown for each patient in Table 1. The mean age of the children was 6.8 years (2–11 years). Nine children (82%) were male, and 10 of the treated eyes (91%) were right eyes. Eight children were treated for anisomyopia, and 3 for anisohyperopia. Nine children (82%) required general anesthesia. Ten (91%) of 11 patients were followed up at 12 months. Mean follow-up time was 11.9 months (6 – 12 months) (Table 2). No anesthetic complications occurred. All patients were discharged promptly, usually within 1 hour of the procedure.
Refraction (SE)
INDIVIDUAL PREOPERATIVE AND POSTOPERATIVE DATA
Age (Yrs)
RESULTS
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Intended Refractive Treatment (SE) Preoperative Data
TABLE 1. Preoperative and Postoperative Results of All Treated Patients
Ocular Alignment (PD)
Corneal Centration (mm)
Haze (0–4⫹)
Amblyopia Therapy Compliance
patch was placed over the eye until the patient was awake and coherent. The postoperative medical regimen included topical ofloxacin (Ocuflox) and loteprednol 0.5% (Lotemax) four times a day until the corneal epithelium healed. Topical ketorolac was prescribed up to four times a day as needed for moderate discomfort for the first 2 postoperative days. Hydrocodone oral elixir (Lortab) was available as needed for severe discomfort in the first week. Loteprednol was changed to fluorometholone 0.25% (FML forte) after 1 week. Patients used the fluorometholone four times a day for 1 month and then underwent a slow taper over the next 5 months. Patients were examined daily until corneal epithelial healing was complete, which occurred by 3 days in the myopic group and by 5 days in the hyperopic group.18 The contact lens was then removed. The patients were examined 1 month after the procedure and then every 3 months for 12 months. Refractive correction was prescribed as needed at the 1-month examination. Occlusion therapy was recommended up to 8 hours per day for the sound eye based on the child’s age and visual deficit. Compliance was assessed at each follow-up visit by asking the parent directly using a compliance scale developed by the Pediatric Eye Investigator Group for the Amblyopia Treatment Study.7 Data collected at each follow-up examination included stereoacuity, uncorrected and best spectaclecorrected visual acuity, ocular motility, degree of corneal haze, and cycloplegic refraction. Postoperative subepithelial corneal haze was graded on a scale of 0 to 4⫹ (0 ⫽ clear cornea; 1⫹ ⫽ trace haze, only detectable with tangential illumination, 2⫹ ⫽ mild, discrete haze visible with difficulty by focal illumination, 3⫹ ⫽ moderately dense opacity partially obscuring iris detail; 4⫹ ⫽ dense opacity obscuring details of intraocular structures). Postoperative corneal topography was performed as patient cooperation allowed at the 12-month visit. Centration was determined using tangential maps from the Humphery Atlas according to the method described by Lin and coauthors.19
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TABLE 2. Patient Characteristics/Refractive Results
Number of patients General anesthesia Mean age in years (range) Mean preoperative K readings ⫾ SD Mean preop corneal thickness ⫾ SD Mean preoperative SE ⫾ SD Maximum refractive SE treatment Mean target SE ⫾ SD Mean 12-month postoperative SE ⫾ SD Mean 12-month target SE reduction ⫾ SD Mean 12-month SE reduction ⫾ SD Mean SE regression ⫾ SD % within 1 D of target at 12 months % within 2 D of target at 12 months % reduction in refractive error
Myopia Group
Hyperopia Group
8 8 4 (3–8) 44.80 D ⫾ 1.54 D 521 ⫾ 43.4 ⫺13.7 ⫾ 3.77 D ⫺11.50 D ⫺3.5 ⫾ 3.75 D ⫺3.3 ⫾ 2.5 D 10.10 D ⫾ 1.39 D 10.56 ⫾ 3.00 D 2.50 ⫾ 2.23 D 50% 63% 76%
3 1 9 (8–12) 42.30 D ⫾ 1.06 D 536 ⫾ 4.24 ⫹4.75 ⫾ 0.50 D ⫹5.25 D plano ⫹1.00 ⫾ 0.5 D 4.75 D ⫾ 0.5 D 4.08 ⫾ 0.8 D 1.10 ⫾ 1.6 D 67% 100% 79%
K ⫽ keratometry; SD ⫽ standard deviation; SE ⫽ spherical equivalent.
● REFRACTIVE ERROR RESULTS-MYOPIA GROUP:
Table 2 shows demographics and complete refractive results. The mean preoperative spherical equivalent in the myopic group was ⫺13.70 ⫾ 3.77 diopters. The mean final target spherical equivalent was ⫺3.50 ⫾ 3.75 diopters. The mean 12-month postoperative myopic spherical equivalent was ⫺3.30 ⫾ 2.50 diopters. The mean target refractive error reduction was 10.10 ⫾ 1.39 diopters of myopia. The mean refractive error reduction at 12 months was 10.56 ⫾ 3.00 diopters of myopia (Table 2, Figure 1A). The mean spherical equivalent difference between the 12-month target and 12-month achieved refractive change after myopic PRK was 0.18 ⫾ 3.5 diopters of overresponse. No patient had an over-response that created hyperopia. Four myopic individuals (50%) were within 1 diopter of target refractive spherical equivalent and five (63%) were within 2 diopters (Figure 1A). There were two patients who were highly myopic preoperatively who achieved a greater degree of correction than targeted. One patient (patient 7) with a preoperative spherical equivalent refractive error of ⫺21.00 diopters had a refractive target reduction of 11.50 diopters and ended up with the final refractive reduction of 16.75 diopters and a 12-month spherical equivalent result of ⫺4.75 diopters. The other (patient 3), with a preoperative spherical equivalent refractive error of ⫺13.75 diopters had a refractive target reduction of 10.50 diopters and at 12 months ended up with the final refractive reduction of 13.25 diopters and a final spherical equivalent result of ⫺0.50 diopters. Refractive error stability over the follow-up period is outlined in Figure 2A. Our myopic group had mild to moderate refractive regression over the 12-month folVOL. 138, NO. 1
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low-up period, with a mean spherical equivalent regression of 2.50 ⫾ 2.23 diopters over the 12-month follow-up. ● REFRACTIVE ERROR RESULTS–HYPEROPIA GROUP:
The mean preoperative spherical equivalent in the hyperopic group was ⫹4.75 ⫾ 0.5 D. The mean final target spherical equivalent in this group was plano. The mean 12-month postoperative hyperopic spherical equivalent was ⫹1.00 ⫾ 0.5 diopter. The mean target refractive error reduction was 4.75 ⫾ 0.5 diopters. The mean refractive error reduction at 12 months was ⫹4.08 ⫾ 0.8 D diopters (Table 2, Figure 1B). The mean spherical equivalent difference between the 12-month target and 12-month achieved refractive change after hyperopic PRK was 0.96 diopters of under-response. Two hyperopes (67%) were within 1 diopter of target spherical equivalent, and all were within 2 diopters (Figure 1B). Refractive error stability over the follow-up period is outlined in Figure 2B. Our hyperopic group showed mild refractive regression as well with a mean spherical equivalent regression of 1.10 ⫾ 1.60 diopters over the 12-month follow-up interval. ● CORNEAL HAZE AND TOPOGRAPHY:
The mean corneal haze measurement 12 months after surgery was 0.50⫹ (0 to 2⫹) (Figure 3). All but one child with residual corneal haze were myopic. Only one patient had mild to moderate corneal haze (2⫹). This child had not been compliant with the postoperative treatment protocol. He did not return for follow-up after the 1-month examination until the 12-month examination and discontinued the fluorometholone drops 1 month after the
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FIGURE 2. (A) Refractive error stability over time (myopic subgroup). (B) Refractive error stability over time (hyperopic subgroup) SE ⴝ spherical equivalent.
FIGURE 1. (A) Refractive treatment goal compared with the 12-month results (myopic children). Note that the points above the line represent over-response from target and those below the line represent under-response from target. (B) Refractive treatment goal compared with the 12-month results (hyperopic children). Note that the points above the line represent overresponse from target and those below the line represent underresponse from target.
surgery. The remainder of the patients had only minimal or no haze. Corneal topography was performed on five patients, and the amounts of decentration are shown in Table 1. The full results have been published elsewhere.16 The mean decentration was 0.60 ⫾ 0.27 mm.
FIGURE 3. Corneal haze at 1 month and 12 month postoperatively. Patients without a bar in the graph at either visit had no haze at that visit.
● VISUAL ACUITY:
In the eight patients able to perform psychophysical acuity tests preoperatively and postoperatively, uncorrected visual acuity improved by 2 or more lines in six eyes (75%) with the maximum improvement of seven lines (Figure 4A and Table 3). In this same group, best spectacle-corrected visual acuity improved at 12 months by 2 or more lines in three eyes (38%) and remained within 1 line of the preoperative visual acuity in four eyes (50%). One patient with a preoperative logarithm of the minimal angle of resolution visual acuity of 1 (20/200) lost acuity to the level of logarithm of the minimal angle of resolution 1.3 (20/400). This is the child who discontinued the topical corticosteroids postopera-
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tively at 1 month and had the highest level of corneal haze at 12 months (Figure 4B). ● STEREOACUITY, OCULAR ALIGNMENT, AND AMBLYOPIA THERAPY COMPLIANCE: Stereopsis was testable in nine
children. Six had no measurable stereoacuity before or 12 months after the treatment using the Titmus fly test. Three patients realized an improvement in stereopsis. One improved from 800 seconds to 50 seconds of arc stereo, another improved from 400 seconds to 60 seconds of arc stereo, and the last patient improved from no measurable stereopsis to 140 seconds of arc stereo. Ocular alignment did not change OF
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TABLE 3. logMAR Equivalents Snellen
logMAR Equivalents
20/20 20/30 20/40 20/50 20/60 20/80 20/100 20/200 20/600 20/2000
0.0 0.2 0.3 0.4 0.5 0.6 0.7 1.0 1.5 2.0
logMAR ⫽ logarithm of the minimal angle of resolution.
FIGURE 4. (A) Comparison of preoperative and 12-month postoperative uncorrected (logMAR) visual acuity. As examples on the logMAR scale, 20/20 is equivalent to 0, and 20/200 is equivalent to 1.0. The closer the value is to zero, the better the visual acuity. Points below the line represent improved postoperative visual acuity and points above the line represent reduced postoperative visual acuity. (B) Comparison of preoperative and 12-month postoperative best spectacle-corrected logMAR visual acuity. Points below the line represent improved postoperative visual acuity, and points above the line represent reduced postoperative visual acuity.
postoperatively in any patient. Compliance with amblyopia occlusion therapy did not improve postoperatively.
DISCUSSION ANISOMETROPIA IS A MAJOR CAUSE OF AMBLYOPIA.4 –7
Compliance with treatment is often poor because the sound eye usually sees well without refractive correction. Refractive surgery in children may be a viable treatment option for children with significant anisometropia, especially when compliance issues arise. VOL. 138, NO. 1
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Both LASIK and PRK have been shown in several studies to be safe in children.8 –10,12–14,16 Most published studies have been done outside the United States and have predominantly included children aged 7 years and older.8 –10,12–14,16 Only one published report to date has included a number of children younger than 7 years of age.13 By 7 to 8 years of age, amblyopia is less likely to respond to therapy, because the period of visual cortical plasticity has passed. Ideally, amblyopia should be treated as early in life as possible. If refractive surgery is to play an active role in treatment of anisometropic amblyopia, it is likely that it too will need to be applied early in life. Our pilot study included 11 patients aged 2 to 11 years, with roughly 50% under 6 years of age. These are some of the youngest children reported to date that have undergone a refractive procedure. We chose to perform PRK instead of LASIK in our pilot study, because we felt it was the safer of the two procedures. We understand that potential advantages of LASIK over PRK in adults have been reported, such as faster recovery of vision, less discomfort, maintenance of an intact Bowman membrane, and, possibly, a more predictable outcome with higher levels of myopia.8 Laser in situ keratomileusis, however, has more serious potential longterm complications, such as corneal flap dislocation, flap striae, and late keratoectasia. After evaluating the risks and benefits of each procedure, we selected PRK as the refractive procedure for our children. The refractive goal in our study was to reduce the amount of anisometropia to less than or equal to 3 diopters. The aniseikonia would then be reduced to the point where fusion was possible and amblyopia may be more amenable to occlusion therapy. We chose not to treat the full amount of myopia in our patients with greater than ⫺11.50 diopters of spherical equivalent myopia, because PRK for these higher levels of myopia has been associated with significant corneal haze in adults. Interestingly and beneficially, two patients with extremely high FOR
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levels of myopia (spherical equivalent of ⫺21.00 diopters and ⫺13.75 diopters) had larger than expected responses to the PRK dose, bringing their final refractive errors to ⫺4.75 diopters and ⫺0.50 diopters, respectively. Both were within 3 diopters of each child’s fellow eye. Why this over-response occurred in our extremely high myopic individuals is not known. Williams noted this same result in adults with refractive errors greater than ⫺10.00 diopters.20 Astle and associates13 also noted this same result in his series of highly myopic children treated with PRK. Reduced scleral rigidity and a difference in corneal remodeling in the highly myopic eye may play a role in both adults and children with extremely high levels of myopia. With further study, if this outcome is found to be consistent in extremely high myopia, modification of the treatment nomograms would be indicated. In our myopic subgroup, 50% of the patients were within 1 diopter of the refractive target and 63% were within 2 diopters. The mean preoperative refractive error of ⫺13.70 diopters was reduced to a mean postoperative refractive error of ⫺3.30 diopters. These results are in agreement with those found in previous studies of PRK in myopic children, though our cohort included younger children than most.11–14 They also are in line with results reported from adults with similar levels of extremely high myopia treated with PRK.21–22 In our hyperopic group, 67% of the patients were within 1 diopter of the refractive target and all were within 2 diopters. The mean preoperative refractive error of ⫹4.75 diopters was reduced to a mean postoperative refractive error of ⫹1.00 diopter. These results are also is in agreement with the data from the only other published study that included pediatric hyperopic PRK.12 Our myopic group had moderate refractive regression over the 12-month follow-up period with a mean spherical equivalent regression of 2.50 diopters over the 12-month follow-up (Figure 2A). This result is in line with the refractive regression seen in high myopic adults treated with PRK.23–25 Other studies in children treated with PRK for myopia have shown a myopic shift (i.e, regression) ranging from 0.8 diopters to 1.7 diopters over a 1-year period.11,14 Our hyperopic group showed mild refractive regression as well with a mean spherical equivalent regression of 1.10 diopters over the 12-month follow-up interval. This regression again is in line with that found in adult hyperopic PRK.26 Four (36%) of our study patients had a minimal degree of residual corneal haze, and one child had mild to moderate corneal haze 1 year after surgery. All but one of these children were high myopic individuals. The child in our study with the mild to moderate haze (patient 5) was the patient who was noncompliant with the postoperative topical corticosteroid regimen. High degrees of corneal haze have also been reported in adults with high myopia treated with PRK.23 Only the child with the mild to moderate corneal haze lost 1 line of best spectacle-corrected visual acuity. All others (88%) had stable or improved visual acuity. 76
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Alio reported that corneal haze was the main optical complication after pediatric PRK but that it decreased by 1 year.11 Approximately 30% of children treated with PRK in Alio’s study had mild corneal haze 1 year after surgery; 80% were high myopic patients. In the only study that included hyperopic PRK in children, corneal haze was not a problem.12 Corneal haze in children treated with PRK has been reported to diminish considerably after 1 year.11 Our patients fortunately did not experience significant corneal haze. Our low incidence of corneal haze may be attributable to the longer use of topical corticosteroids, or it could be attributable to improvements in excimer laser technology. In our cohort, we used the VISX Star S2 laser, a third-generation excimer laser. Older studies used first-generation broad-beam excimer lasers.11–12 Most patients enjoyed improved uncorrected visual acuity and best spectacle-corrected visual acuity. Only one patient lost best corrected visual acuity; all others either improved or maintained their acuity. We felt the loss in acuity in this patient was because of corneal haze resulting from noncompliance with the postoperative topical corticosteroid regimen. Our acuity results are in accordance with the published results in adult patients treated with PRK.24,26 –27 Conversely, our result are somewhat surprising because most of the children had profound long-standing amblyopia and 45% of them were 7 years old or older, typically beyond the sensitive period of visual development. We feel that if refractive surgery were performed at an earlier age, before severe amblyopia has occurred, long-term visual outcomes would probably be markedly better. As an example, our youngest patient, who preoperatively at age 2 years could only be visually tested preoperatively with fix and follow testing, had a bestcorrected visual acuity of 20/40 at the 12 months’ postoperative visit despite his continued lack of compliance with spectacle use and amblyopia therapy. Based on our experience with other patients with similar levels of anisometropia and poor compliance, his visual acuity would most likely have been significantly worse in this eye if refractive surgery had not been done. Stereoacuity improved in one third of our testable cohort. This was an unexpected and encouraging finding, as most of our patients were well beyond 2 years of age, the age at which most ophthalmologists feel stereopsis development is complete. All children in our study who required general anesthesia had their procedure in an operating room at our children’s hospital without an adverse complication.17 As long as the idiosyncrasies of the excimer laser are addressed, excimer laser procedures can be performed accurately, safely, and efficiently under general anesthesia. The 193-nm wavelength of the argon fluoride excimer laser lies within the absorption spectrum of many anesthetic gases, including nitrous oxide. If a volatile gas escapes, attenuation of the laser beam occurs and the laser increases voltage in an effort to maintain fluence until the laser stops firing and an error message appears. OF
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Because of these issues, we used an LMA and a specific induction procedure outside of the operating room and had no problems with the functioning of our laser. Centration is another potential problem with excimer laser procedures performed under general anesthesia. Centration in our study patients was adequate. Our centration results are within the acceptable range, achieved in most by using observers on either side of the eye to ensure that the iris plane was maintained perpendicular to the laser beam.17 The one exception was one hyperopic patient with a decentration of 1.05 mm. This child’s postoperative uncorrected visual acuity was 20/50 and her best spectaclecorrected visual acuity was 20/30 in this eye. Fixation devices such as the Arrowsmith fixation ring were considered but not used, because we found our protocol with the two observers to be reliable. Perhaps a fixation ring could better ensure centration when performing the larger hyperopic ablations, however, there were too few patients in this study to draw any definite conclusions. The VISX Star S2 laser we used did not have an eye tracking system. An eye tracking system would probably not be that useful under general anesthesia, as it only ensures centration on the pupil and does not guard against an oblique contact of the laser beam on the cornea. The observers ensured this perpendicular entry in our study patients. Our procedure, though effective, was cumbersome and labor intensive. If refractive procedures become more commonly performed under general anesthesia, a device that maintains the laser beam normal to the anterior corneal surface may be of use. In summary, our 12-month results demonstrate that PRK appears to be safe for the treatment of anisometropia in children. The refractive error response in children appears to be similar to that of adults with comparable refractive errors; therefore, nomogram modification may not be necessary. Consideration of the expected immediate over-response in patients with extreme degrees of refractive errors, however, might be needed. More experience is needed with larger patient numbers to be able to adequately address this question, especially in terms of the patients with profound myopia. Most importantly, PRK for anisometropic amblyopia can result in improved uncorrected visual acuity, best spectacle-corrected visual acuity, and stereopsis, even in older children who are typically thought to be visually mature. Long-term follow-up for all of these issues is indicated before PRK and other refractive procedures can be recommended for general use in the pediatric population. If long-term safety can be demonstrated, then PRK may play an important role in earlier treatment of anisometropia before severe amblyopia has developed.
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2. Nagy ZZ, Krueger RR, Suveges I. Photorefractive keratectomy for astigmatism with the Meditec MEL 60 laser. J Refract Surg 2001;17:441–453. 3. Griffith M, Jackson WB, Lafontaine MD, Mintsioulis G, Agapitos P, Hodge W. Evaluation of current techniques of corneal epithelial removal in hyperopic photorefractive keratectomy. J Cataract Refract Surg 1998;24:1070 –1078. 4. Greenwald MS, Parks M. Amblyopia: In: Tasman W, Jaeger EA, editors: Duane’s clinical ophthalmology. Chapter 10. Philadelphia: JB Lippincott, 1994:1. 5. Mittelman D. Amblyopia. Pediatr Clin North Am 2003;50: 189 –196. 6. LaRoche GR. Amblyopia: detection, prevention, and rehabilitation. Cur Opin Ophthalmol 2001;12:363–367. 7. Repka MX, Beck RW, Holmes JM, Birch EE, Chandler DL, Cotter SA, Hertle RW, Kraker RT, Moke PS, Quinn GE, Scheiman MM, Pediatric Eye Disease Investigator Group. A randomized trial of patching regimens for treatment of moderate amblyopia in children. Arch Ophthalmol 2003;121:603–611. 8. Rashad KM. Laser assisted in situ keratomileusis for myopic anisometropia in children. J Refract Surg 1999;15:429 –435. 9. Agarwal A, Agarwal A, Agarwal T, et al. Results of pediatric laser in situ keratomileusis. J Cataract Refract Surg 2000;26: 684 –689. 10. Nucci P, Drack AV. Refractive surgery for unilateral high myopia in children. J AAPOS 2001;5:348 –351. 11. Alio JL, Artola A, Claramonte P, Ayala MJ, Chinpont E. Photorefractive keratectomy for pediatric myopic anisometropia. J Cataract Refract Surg 1998;24:327–330. 12. Singh D. Photorefractive keratectomy in pediatric patients. J Cataract Refract Surg 1995;21:630 –632. 13. Astle WF, Huang PT, Ells AL, Cox RG, Deschenes MC, Vibert HM. Photorefractive keratectomy in children. J Cataract Refract Surg 2002;28:932–941. 14. Nano HD, Muzzin S, Irigary LF. Excimer laser photorefractive keratectomy in pediatric patients. J Cataract Refract Surg 1997;23:736 –739. 15. Rybintseva LV, Sheludchenko VM. Effectiveness of laser in situ keratomileusis with Nidek EC-5000 excimer laser for pediatric correction of spherical anisometropia. J Refract Surg 2001;17(suppl):S224 –S228. 16. Autrata R, Rehurek J. Clinical results of excimer laser photorefractive keratectomy for high myopic anisometropia in children: four-year follow-up. J Cataract Refract Surg 2003;29:694 –702. 17. Paysse EA, Hussein MAW, Koch DD, Wang L, Brady McCreery KM, Glass NL, Hamill MB. Successful Implementation of a Protocol for Photorefractive Keratectomy in Children requiring General Anesthesia. J Cataract Refract Surg 2003;29(9):1744 –1747. 18. Paysse EA, Hamill MB, Koch DD, Hussein MAW, Brady McCreery K, Coats DK. Epithelial Healing and Ocular Discomfort Following Photorefractive Keratectomy in Children. J Cataract Refract Surg 2003;29:478 –481. 19. Lin DT, Sutton HF, Berman M. Corneal topography following excimer photorefractive keratectomy for myopia. J Cataract Refract Surg 1993;19(suppl):149 –154. 20. Williams DK. Multizone photorefractive keratectomy for high and very high myopia: long-term results. J Cataract Refract Surg 1997;23:1034 –1041. 21. Shah S, Chatterjee A, Smith RJ. Predictability of spherical photorefractive keratectomy for myopia. Ophthalmology 1998;105:2178 –2184. 22. Heitzmann J, Binder PS, Kassar BS, Nordan LT. The FOR
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correction of high myopia using the excimer laser. Arch Ophthalmol 1993;111:1627–1634. 23. Tabbara KF, El-Sheikh HF, Sharara NA, Aabed B. Corneal haze among blue eyes and brown eyes after photorefractive keratectomy. Ophthalmology 1999;106:2210 –2215. 24. Kim JH, Kim MS, Hahn TW, Lee YC, Sah WJ, Park CK. Five years results of photorefractive keratectomy for myopia. J Cataract Refract Surg 1997;23:731–735. 25. Hersh PS, Stulting RD, Steinert RF, Waring GO 3rd, Thompson KP, O’Connell M, Doney K, Schein OD, The
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