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Doi:10.1016/j.jaapos.2005.01.006

Correction of Large Amblyopiogenic
Refractive Errors in Children Using the
Excimer Laser
Lawrence Tychsen, MD, Eric Packwood, MD, and Gregg Berdy, MD
Purpose: We sought to determine whether laser subepithelial keratomileusis (LASEK) and photorefractive
keratectomy (PRK) are effective methods for correcting amblyopiogenic refractive errors in children. Methods:
Thirty-six eyes in 35 amblyopic children, who ranged in age from 4 to 16 years (mean, 8.4 years), received
treatment for large magnitude ametropia. Seventy-two percent (25/35) of the children had a neurobehavioral
disorder and/or were noncompliant with spectacle or contact lens wear. Myopia ranged from Ϫ3.25 to Ϫ24.25 D
(mean, Ϫ11.48 D); one patient had hyperopia of ϩ5.87 D. Correction was tailored to match the refractive error of
the nonamblyopic eye. VISX Star S2/S3 excimer lasers were used in manual or auto-tracking modes, and corneal
centration was achieved using brief, general anesthesia. Mean follow-up was 29.2 months (range, 4-42 months).
Results: Myopia correction averaged Ϫ8.95 Ϯ 2.89 D (range, Ϫ3.25 to Ϫ15.50). Eighty-nine percent (31 children)
were corrected to within Ϯ 1.00 D of goal refraction and the remaining 11% to within 2.0 D of the goal (most were
undercorrected). Acuity improved postoperatively in 97%; by 1 optotype line in 37% and by 2 or more in 60%. No
child lost acuity. Binocularity improved in 69% (24/35) and remained the same in 31%. Corneal haze measured
grade 0-1 in 78%, grade 2 in 14%, and grade 3-4 in 8%. Myopic regression exceeding Х 1.0 D/year (0.08 D/month)
occurred in 50% (18/36) of eyes treated. No substantial differences were observed in PRK- (n ϭ 18) versus LASEK-
(n ϭ 17) treated children. Conclusions: Laser refractive surgery is effective for correcting anisometropic myopia
in amblyopic children. Recurrence of myopia is common. Further study is indicated to determine long-term stability
and safety of the procedure in this population.
T he management of large magnitude ametropia in tropia also may produce a degree of cosmetic disfigure- children remains a challenge to pediatric ophthal- ment, subjecting school age children to social ridicule.
mologists. Nonsurgical measures for correcting Contact lens correction can circumvent these disadvan- ametropia are spectacles and contact lenses. Patients with tages but may not be tolerated or practical in many chil- unilateral ametropia generally are suitable for spectacle dren, particularly those with neurobehavioral disorders.
correction, but this method of correcting high degrees of Excimer laser correction of refractive errors has been anisometropia causes lens-induced aniseikonia and, in ec- shown to be effective and safe in but the use of centric gazes, disconjugate shifting of images caused by this method in children has been the subject of a limited prismatic effects induced by thick Both of these number of case In adults, the excimer laser factors produce binocular image decorrelation, impeding technique most widely used (laser-assisted in situ kerato- binocular fusion and the optimal correction of anisome- mileusis, or LASIK) entails the creation of a corneal stro- tropic Spectacle correction of high anisome- mal flap using a mechanical blade or blade-equivalent laserAfter the reshaping of the corneal stromato correct ametropia, the flap is repositioned and is held inplace by initially tenuous, natural biomechanical bonds.
From the Department of Ophthalmology and Visual Sciences, St. Louis Children’s Hospital, After LASIK flap repositioning, manipulation of the eye at Washington University School of Medicine, St. Louis, Missouri.
Presented at the American Association for Pediatric Ophthalmology and Strabismus 30th
must be avoided to reduce the risk of flap displacement, a Annual Meeting, Washington, DC, March 2004, and in part at The Association for Research in Vision & Ophthalmology Annual Meeting, Fort Lauderdale, Florida, May a LASIK flap also diminishes the magnitude of correction 2002.
Submitted March 9, 2004.
that may be achieved by laser ablation because a sufficient Revision accepted January 25, 2005. bed of nonablated stroma must remain to ensure long- Reprint requests: Lawrence Tychsen MD, St. Louis Children’s Hospital at Washington University School of Medicine, One Children’s Place, Suite 2S-89, St. Louis, MO 63110.
E-mail: tychsen@vision.wustl.edu.
The surface-ablation procedures photorefractive ker- Copyright 2005 by the American Association for Pediatric Ophthalmology and atectomy (PRK) and laser subepithelial keratomileusis (LASEK) circumvent these disadvantages because they 1091-8531/2005/$35.00 ϩ 0doi:10.1016/j.jaapos.2005.01.006 do not require creation of a stromal flap. PRK/LASEK 224
June 2005
Journal of AAPOS
Journal of AAPOSVolume 9 Number 3 June 2005 TABLE 1 Refractive goal, outcome, and regression in 35 PRK- or LASEK-treated children (36 eyes)
Init Postop
refraction
refraction
Final postop
regression†
surgery/sex
Preop refraction
technique*
(diopters)
(diopters)
refraction
*40 micron phototherapeutic keratomileusis (PTK)/photorefractive keratomileusis (PRK); Man: manual scrape.
†D/mo: average diopters per month.
are used to correct high ametropia in The patients into 3 groups on the basis of the laser surgical techniques also have been used to correct ametropia in technique used: combined phototherapeutic keratectomy a small number of pediatric case The purpose (PTK) and PRK (patients 1-12), manual removal of epi- of this report is to communicate our experience using thelium and PRK (patients 13-18), or LASEK (patients PRK and LASEK to correct ametropia in a sizable 19-35). The mean age at surgery was 8.4 years; range 4-16 cohort of anisometropic children. A preliminary report years. One third (39%, 14/36) of eyes treated were in of a portion of these data was published in 2002 as an patients 7 years of age or younger at the time of laser correction, and 72% (26/36) were age 10 years of age oryounger. One child had follow-up for 3 months but did PATIENTS AND METHODS
not return for longer follow-up and is therefore not listed Clinical outcome data displayed in and were in the Tables of 35 children (36 eyes) reported in our collated from a prospective study of 36 consecutive eyes in results. One child had sequential correction of high myo- 35 ametropic children (17 boys, 18 girls). All surgery was pia in both eyes, and these results are reported (patient 22, performed at St. Louis Children’s Hospital between June age 5 years). Mean follow-up was 29.2 months (range, 4-42 TABLE 2 Visual acuity, binocular function, visuomotor findings, and neurobehavioral status of the 35 treated children (36 eyes)
Ocular and visuomotor
Neurobehavioral
Preop VA*
Postop VA
binoc†
status§
status¶
ET surg ϫ 2; MLNregressed ROP, disctilt ϩ drag retina OU aniso ϩ strab amb,cryo OS ROP, congptosis rep OS amb, neonatal vithemorr LE, inf sens ETsurg ϫ 3, MLN ϫ1; bilat Iris colob ϩmicrocornea; Inf retinalcolob OD Journal of AAPOSVolume 9 Number 3 June 2005 TABLE 2 Continued
Ocular and visuomotor
Neurobehavioral
Preop VA*
Postop VA
binoc†
status§
status¶
amb; cong cat surgage 2 mo; 2* IOL age5; inf ET surg ϫ 3;microcornea OS ϩ aniseikonicdiplopia w/spec,noncompliant *VA: visual acuity; Best corrected optotype (Snellen fraction) if tolerated spectacles, uncorrected otherwise; SSEP: spatial-sweep evoked potential.
†fus vrg: fusional vergence response to base-out prism; W4D: Worth four-dot test fusion; stereo-Titmus/Randot responses.
‡Haze at last f/u exam, except for retreated pt 14 (see text).
§ROP: retinopathy of prematurity; MLN: manifest latent nystagmus; ET: esotropia; XT: exotropia; IOL: intraocular lens¶DD: developmental delay; ADHD: attention deficit hyperactivity disorder; CP: cerebral palsy; PDD: pervasive developmental disorder; MR: mental retardation.
Each child had a minimum of 2 office examinations research and was approved by the Washington University performed preoperatively, as well as examination-under- anesthesia (EUA) at the laser procedure. The examinationsincluded age-appropriate testing of visual acuity in each Indications and Contraindications
eye, pupillary examination with measurement of diameter, Indications for laser correction included (1) anisometropia sensorimotor examination of eye alignment/eye move- greater than 4.00 D or bilateral ametropia greater than ment/binocular function, a minimum of 2 manual and, 5.00 D; (2) children noncompliant with spectacle wear or when feasible, automated cycloplegic refractions per- intolerant of or ill-suited for contact lens wear; (3) ambly- formed within 1 week, slit lamp biomicroscope evaluation opia in the candidate eye equivalent to 2-optotypte-lines of the anterior segment and assessment of tear film, indi- or worse; (4) absence of glaucoma, uveitis, recurrent con- rect ophthalmoscopy, and measurement of intraocular junctivitis, tear film insufficiency, endothelial dysfunction/ pressure with a Tonopen (Minter O&O, Norwell, MA).
corneal dystrophy, corneal scarring, keratitis, or systemic Automated photokeratoscopy mapping was performed be- inflammatory disease; (5) pachymetry exceeding 425 mi- fore and after the surgery in cooperative children. Addi- crons but less than 675 microns; and (5) good rapport with tional measurements obtained under anesthesia immedi- the child’s parent(s), who acknowledged the risks/alterna- ately before the laser procedure included pachymetry, tives and the importance of follow-up examinations.
keratometry, corneal diameters, biomicroscopy with go-nioscopy, and A-scan ultrasonographic axial length mea- Outcome Measures
surement. The amount of desired correction was adjusted Principal outcome measures included postoperative best- (unless otherwise noted) to conform to the refractive error corrected and/or uncorrected visual acuity, postoperative refractive error, refractive regression, postoperative binoc- Written informed consent was obtained from the par- ularity, corneal haze, and complications. Binocularity was ent(s). The consent document itemized the rationale for graded as lowest-to-highest using the following 3-tiered and potential risks of pediatric excimer laser surgery, the scale: presence of a fusional vergence response to a 20 need for continuing amblyopia therapy, and the possible diopter base-out prism; fusion of the Worth (Lombart need for additional surgery. The protocol complied with Norfolk, VA), or Polaroid (Lombart Norfolk, VA) 4-dot the ARVO resolution on the use of human subjects in test; and stereoscopic sensitivity scored by the Titmus Stereotest (Titmus, Peterburg, VA). Postoperative corneal For PTK-mode removal of the epithelium, the micro- haze was graded on a scale of 0 to 4, with 0 representing no scope was adjusted and the aiming beam laser reticule was haze and grades 1-4 indicating increasing density of centered in the pupil, ablating the cornea over a diameter of 6.5 mm to a depth of 40 microns in a period of approx- Outcome measures were those obtained at the most imately 20 seconds. A Took knife (Storz Instruments, recent follow-up examination for refractive error, regres- Bausch & Lomb, Rochester, NY) was scraped across the sion, haze, and complications. Outcome measures for vi- ablation zone to verify absence of epithelium. For manual sual acuity and binocularity were the lowest value or grade removal, the Took knife alone was used. For LASEK, the recorded in the interval of 1 month after surgery to the trephine was removed and replaced with the 8.5-mm di- most recent follow-up examination. The postoperative ameter well, which was filled with 20% alcohol diluted in acuities reported were best-corrected if the child wore sterile water, ensuring that the central epithelium was refractive correction at home or in school, and uncor- submerged fully. The alcohol was removed using a Mero- rected if the child would not permit spectacle wear because cel sponge after 30 seconds, followed by irrigation of the of a neurobehavioral disorder or chronic noncompliance conjunctiva and cornea. The central 8 mm of epithelium with spectacle wear. These conservative conventions were was removed with the micro-hoe, scrolling the tissue in adopted to deliberately bias outcomes in the direction of rolled-carpet fashion from the 6-o’clock to 12-o’clock po- sition, where it remained hinged (treatment zone diameter avoided ascribing to laser correction any improvements was 1.0 mm larger for the hyperopic correction).
that could have resulted from on-going amblyopia therapy After de-epithelialization, the microscope was adjusted in children 10 years of age or younger, (2) incorporated to 16X and the aiming reticule again centered in the pupil.
any deficits that accrued because of progressive haze or A Merocel stick microsponge moistened with balanced salt refractive regression, and (3) provided the most realistic solution was brushed across the corneal stroma to dull the estimate of the visual gain achieved by laser correction for reflex. Manual or autotracking PRK was completed using regular/blend treatment zones of 6.0/8.0 mm over a courseof 60-90 seconds. After each 20-25 seconds of laser appli- Surgical Procedure
cation, the treatment was interrupted and a microsponge All surgeries were performed under general anesthesia employed to wipe and barely moisten the ablation zone. In using standard pediatric techniques. Induction was con- LASEK-treated children, the rolled carpet of epithelium ducted by mask inhalation of a volatile anesthetic mixture was unscrolled from the 12-o’clock position and smoothed (nitrous oxide/sevoflurane/oxygen) followed by insertion back over the stroma using a micro-spatula. Voltaren (No- of a laryngeal mask airway and conversion to total intra- vartis Ophthalmics, Inc., Duluth, GA), Ciloxan (Alcon venous anesthesia (TIVA, using propofol). Ketorolac Laboratories, Fort Worth, TX), TobraDex (Alcon Labo- tromethamine was administered intravenously to reduce ratories, Fort Worth, TX), and additional proparacaine eye drops were applied, followed by a plano bandage After the EUA, proparacaine drops were applied to the conjunctiva of the eye selected for treatment. The child’spupil was undilated. Manifest and cycloplegic refraction Postoperative Regimen and Medication Compliance
with sphere, cylinder, and axis as well as the amount of Printed instructions were discussed with and issued to the desired refractive treatment, keratometry readings and family at discharge, including discouragement of removal vertex distance were programmed into the Visx Star S2 or of the Fox shield or eye rubbing, and directions for instil- S3 (VISX USA, Inc., Santa Clara, CA) laser. The depth of lation of eye drops to keep the eye moistened and reduce TIVA was adjusted if necessary to eliminate any tendency the risk of tight lens syndrome, infection, or inflammation.
for globe rotation away from primary position in the orbit The parents also were instructed in the use of optional post- (ie, residual Bell’s reflex). The child’s head was reposi- operative pain medications to include oral Percocet (Endo tioned using a pneumatic beanbag so that the iris remained Pharmaceuticals, Chadds Ford, PA), or Tylenol with codeine level in all planes. Betadine prep was applied to the eyelids elixir (Ortho-McNeil Pharmaceuticals, Raritan, NJ) and oral and conjunctival cul-de-sac. The patient table was swiv- ketorolac. No anesthetic complications occurred in the eled and locked in position under the microscope. Tega- study group, and all of the children were discharged from derm (3M, St. Paul, MN) drapes were applied to the upper the same day surgery unit within 1 hour of the procedure.
and lower eyelids. A lid speculum was inserted. A circular No restrictions were placed on activities.
Merocel (Medtronic Xomed Surgical Products, Inc., Jack- Postoperative examinations were performed at 1 day sonville, FL) sponge soaked in 4% lidocaine was placed on and thereafter at 48-hour intervals until reepithelialization the center of the cornea for 30 seconds and removed. The was complete and there was no evidence of corneal fluo- 8.0 mm diameter trephine was centered on the pupil and rescein staining. If the bandage contact lens was still in applied with gentle downward force to score the corneal place it was removed. Follow-up examinations were per- formed at 1 month, 2-3 months, and then at 6-month Journal of AAPOSVolume 9 Number 3 June 2005 intervals, unless active amblyopia therapy warranted more ing exotropia by a ratio of 1.7:1. An additional 11 children frequent visits. Topical TobraDex and Voltaren drops (31%) had evidence of primary monofixation syndrome.
were used q.i.d. during the first week after surgery. There- Nine of the 35 (26%) displayed conspicuous manifest after, Vexol (Alcon Laboratories, Fort Worth, TX), FML latent nystagmus. Seven of 35 (20%) had a history of diode (Allergan, Inc., Irvine, CA), or prednisolone drops were to laser, cryotherapy-treated, or spontaneously regressed be substituted and used b.i.d. For the last 4 children stage 3 retinopathy of prematurity. Three children (9%) reported in and (patients 32-35), a standard had previous surgery for infantile cataract and intraocular chewable multivitamin containing 60 mg of vitamin C lens implantation in the amblyopic eye (2 of these eyes also (ascorbic acid, 100% of the daily recommended value) was had mild microcornea). One child (patient 27) had bilat- also prescribed each day for a minimum of 6 months in an eral iris colobomas with mild microcornea and a macula- sparing chorioretinal coloboma in the treated eye.
The topical medication compliance data reported was Twenty-five of the 35 children (72%) had a neurobe- estimated by having nonphysician members of the clinic havioral disorder, ranging from moderate to severe. Nine staff query parents, asking them to recall the name or of these children (36%) had a history of prematurity with bottle color of the drop used, any difficulties with drop birth at gestational age of 30 weeks or less. An additional administration, and the need for any refills at each fol- 5 children (14%) had no neurobehavioral disorder but low-up visit. The method was used to avoid embarrassing were chronically noncompliant with spectacle wear. The noncompliant parents/children while enhancing the remaining 5 children (14%) were normal, wore spectacles chances of eliciting candid responses.
for anisometropia exceeding 6.0 D, and either contact-lensfailures or unsuitable for contact lens wear because of Statistical Analysis
Correlation coefficients were calculated for variables that Initial Cornea Epithelium Healing
included: the amount of laser correction, regression rate,corneal haze, age at surgery, and compliance with topical Reepithelialization of the cornea was complete by an av- medication. Outcomes were compared between the three erage 3.6 Ϯ 1.4 days. No substantial difference was noted surgical technique groups by use of analysis of variance in the rate of corneal reepithelialization between groups of (ANOVA) for time to reepithelialization, corneal haze, children treated by PTK/PRK, manual scrape/PRK, or and regression rate. Comparison of improvement in acuity LASEK (analysis of variance [ANOVA], P ϭ 0.388). Two across age group was performed using ANOVA. Differ- of the 35 children (6%) required an oral analgesic for ences between means of unpaired subgroups were mea- discomfort within 24 hours after the procedure but not sured using the t-test. Significance was defined as P Ͻ thereafter. The other 94% (33/35 children) displayed no signs of substantial discomfort or change in behavior,other than photophobia, during the interval of reepitheli- alization. Twenty-six percent (9/35) of the children(mainly but not exclusively those with severe neurobehav- Ocular, Visuomotor, and Neurobehavioral Status
ioral disorders) dislodged the eye shield, manipulated the All of the 35 children reported in our results and listed in eye, and lost the bandage contact lens within 12 hours of the surgery. Lens loss appeared to have no noteworthy anisometropic amblyopia. Nine of these 34 children (26%) effect on the rate of corneal healing or discomfort.
had superimposed strabismic or pattern-deprivation am- blyopia. One child (3%, patient 22) had strabismic ambly- adherent epithelial flap during attempted LASEK and the opia and bilateral isometropic myopia. The preoperative procedure was converted to manual scrape. The mishap acuities reported in range from 20/40 (optotype did not impair corneal healing. Patient 35 had LASEK and fraction 0.5) to 1/200 (0.005) with a mean acuity of 0.23 normal postoperative healing, but experienced acute pain (20/87). Patient 27 had acuity measured only as “fix/fol- and photophobia in the operated eye 1 month after the low,” owing to profound developmental delay/mental re- procedure. He had a ϳ2 ϫ 2-mm region of loose epithe- tardation. All of the children had a history of attempted lium near the edge of the original flap, which was excised amblyopia therapy, including spectacle wear, occlusion under brief anesthesia and retreated with a bandage con- therapy, and/or atropine penalization before enrollment in tact lens. The cornea healed without scarring in 48 hours.
the protocol. Continuing amblyopia therapy was recom-mended in children 10 years of age or younger throughout Refractive Error and Laser Correction
the follow-up interval, but compliance with amblyopia lists the preoperative refraction, goal refraction, and initial postoperative refraction for each of the treated Twenty-one of the 35 children (60%) had strabismus children. Thirty-four of the 35 children were myopic, with (and a history of 1 or more strabismus surgeries), most the preoperative refractive error ranging from Ϫ3.25 to commonly infantile onset, with primary esotropia exceed- Ϫ24.25 D (spherical equivalent [SE], mean Ϫ11.48D).
Thirty-two of the 35 children (91%) also had astigmatism, To reduce the chance of developing haze, topical cor- ranging from 0.50 to 5.50 D (mean, 1.93 D). Treatment ticosteroid drops were prescribed for use twice a day for was tailored to match the spherical refractive error of the the first 6 months after surgery, but compliance after the nonamblyopic eye and eliminate all astigmatism (in patient first month was, on the whole, poor. Mean duration of 22, who had bilateral high isometropic myopia, treatment drop compliance was 1.06 Ϯ 1.08 months. Special efforts in both eyes was targeted to plano). In 20/35 children were made to achieve substantially longer intervals of good (72%), the fellow eye was emmetropic or mildly hyperopic compliance (average 7.0 Ϯ 2.0 months) with topical med- and thus the goal refraction was plano to ϩ 1.00 D. In the ication and oral Vitamin C in the last four children (pa- other 15/35 (28%), the fellow eye was mild-to-moderately tients 32-35) listed in and Haze in this corti- myopic and the goal refraction ranged from – 0.50 to costeroid-plus-vitamin C group was significantly milder – 8.00 D. One child (patient 26) had anisometropic hyper- than that in the remaining LASEK group (unpaired t-test, opia of ϩ5.87 D, with a goal refraction of ϩ1.00 D.
P ϭ 0.034), and 3 of the 4 experienced no myopic regres- Myopic spherical correction (laser treatment achieved) averaged 8.95 Ϯ 2.89 D (range, Ϫ3.25 to Ϫ15.50). Eighty- Three children had corneal haze exceeding 2ϩ (patients nine percent of children (31/35) were corrected to within 6, 14, and 25). Despite the haze (and myopic regression), 1.00D of spherical goal refraction. The remaining 11% (4/35) were corrected to within 2.0 D of the goal (3 of 4 the 3 children achieved minor improvement in visual acu- undercorrected). Correction of astigmatism averaged 1.86 ity. One had PTK, 1 had manual scrape, and 1 had LASEK Ϯ 1.34D, and the initial cylindric correction achieved was removal of the epithelium. Patients 6 and 25 had –10D SE within 1.0D of plano in all 32 astigmatic children.
and – 8.25D SE laser correction, and the families did notinstill eye drops after the first week. Patient 14 had – 6.25 Visual Acuity Outcomes and Ablation Center
D SE laser correction and received TobraDex for 1 Decentration
month, followed by prednisolone 0.125% for 1 year (he Acuity improved postoperatively in 34/35 children (97%) was also treated during the 32-month follow-up interval treated, but the gains were minor (the equivalent of 1 with courses of oral prednisone for asthma). The com- optotype line) in 13 of these 34 children (38%). Improve- bined topical and oral corticosteroid treatment did not ment of 2 optotype lines or more was achieved in 62% prevent the development of 3-4ϩ haze. Thirteen months (21/34). Impressive gains in acuity (Ն 3 optotype lines) after PRK, he was taken back to the operating room for were achieved in patients 2, 5, 12, 19, 22, 24, 29, 31, and scraping of the stromal surface and application of 0.02% 35 (9/35 or 26%). One child (patient 7) had no change in mitomycin The haze cleared to 1-2ϩ and during a acuity; no child lost visual acuity.
3-month period myopic regression reversed by ϩ 1.50D.
Mean gain in acuity (optotype fraction) for the study group was 0.20 Ϯ 0.16. Gains in acuity were comparable Myopic Regression
for children younger than 7 years of age (mean improve- Myopic shift during the follow-up interval is reported in ment 0.18 Ϯ 0.19), for children age 7-10 years ( 0.21 Ϯ as regression rate, expressed as SE diopters per 0.15), and for children older than 10 years of age (0.18 Ϯ month. Twenty-four of the 35 children treated (69%) 0.14; ANOVA; P ϭ 0.421). None of the children com- exhibited some evidence of regression. The average rate of plained of glare, haloes, or other subjective visual distur- regression was – 0.088 Ϯ 0.22 D/month, or –1.06 D/year.
Five children were able to cooperate reliably to com- Myopic regression exceeding Х 1.0 D/year (0.08 pare awake pre- versus postoperative topographic corneal D/month) occurred in 50% (18/36) of eyes treated. Re- maps. The average decentration of the ablation center in gression rates were comparable in children treated by this group was 0.67 mm (range, 0.41– 0.98). No systematic PTK/PRK (Ϫ0.110 Ϯ 0.29 D/month), manual scrape/ trend was evident relating decentration to surgical tech- PRK (Ϫ0.074 Ϯ 0.08 D/month), and LASEK (Ϫ0.079 Ϯ nique used or visual acuity outcome.
0.21 D/month; ANOVA, P ϭ 0.818). The rate of myopicregression correlated with severity of haze (r ϭ 0.356, P Ͻ Corneal Haze
0.001) and younger age at surgery (r ϭ 0.395, P Ͻ 0.0001).
Corneal haze observed during the follow-up interval As noted above, long-term compliance with drops and ranged from zero to 4ϩ, with a mean score of 0.77 Ϯ 0.87 oral vitamin C was associated with less myopic regression.
for the 36 eyes. Corneal haze measured grade 0-1 in 78%, However, the use of topical corticosteroids did not prevent grade 2 in 14%, and grade 3-4 in 8%. No systematic significant regression in all cases. Patient 14 received top- relationship between the surgical technique used and the ical (and intermittently oral) corticosteroids but experi- subsequent occurrence of haze was found (ANOVA, P ϭ enced substantial regression (with significant haze). Pa- 0.363). The severity of haze correlated weakly but signif- tient 32 was compliant with both drops and vitamin C for icantly with the amount of laser correction (r ϭ 0.157; P Ͻ a duration of six months, but also experienced substantial 0.0001) and younger age at surgery (r ϭ 0.115; P Ͻ 0.001).
Journal of AAPOSVolume 9 Number 3 June 2005 TABLE 3 Representative pediatric excimer laser surgery studies for correction of anisometropic myopia
Nucci ؉ Drack
Astle et al.
Autrata ؉ Rehurek
O’Keefe ؉ Nolan
Current study
UK: United Kingdom; US: United States; yr: year; mo: month; PRK: photorefractive keratectomy; LASIK: laser-assisted in situ keratomileusis; LASEK: laser subepithelialkeratomileusis.
*Prevalence in cohort.
†Gain optotype fraction.
‡Medication compliance measured for each child.
Improvement in Binocular Fusion
ble rate of complication is particularly noteworthy in light Binocular fusion improved postoperatively in of the fact that many of the children treated in our study 24/35 children (69%). Mild gains were measured in 19/24 were highly uncooperative owing to neurobehavioral dis- (79%) of these cases, defined as an improvement in one orders. It is prudent to note that less serious complications grade of binocularity, eg from presence of fusional ver- may only appear after prolonged follow-up, and the aver- gence to fusion of the four-dot test. Major gains in bin- age follow-up of the children in this series was two-and- ocularity (defined as improvement of 2 grades) were mea- sured in 5/24 (21%). No child had a deterioration of The major drawback to excimer laser correction in binocularity as a result of laser correction. Patients 5, 18, children is the high prevalence of return of ametropia.
and 29 (33%, 3/9 with nystagmus) had manifest latent Regression occurred in 69% of the children treated, with nystagmus damp to latent nystagmus as a benefit of the an average return of myopia at the rate of ϳ1 D/year.
Regression also was apparent in the hyperopic child at arate ϳ0.5 D/year. Keratocyte-mediated regrowth of the DISCUSSION
photoablated stroma and epithelial hyperplasia appear to The purpose of this study was to review outcomes in a sizable series of children treated by a pediatric ophthal- ment of haze is attributed to high numbers of wound mologist using PRK or LASEK, with the goal of answer- healing keratocytes. Topical corticosteroids reduce regres- ing 2 major questions. Is excimer laser surgery, an effective sion and corneal haze in adult excimer laser way to correct high ametropia in children who, for one The use of systemic ascorbate (vitamin C) may also inhibit reason or another, are not suitable candidates for correc- stromal collagenase, reducing both stromal haze and re- tion by other means? The answer to this question, based on the current study and earlier is yes, when study who received both topical corticosteroid and sys- effectiveness is measured as improvement in acuity or temic ascorbate for at least 6 months after surgery showed ability to achieve a nearly emmetropic refraction. Visual no regression and negligible haze. Further study in a larger acuity improved in 97% of the children in this study group of children will be required to confirm the promis- (substantially in 62%), and we were able to correct the ing results obtained in this subgroup.
ametropia to within 2.0 D of the target refraction in alleyes. The second, equally important, question we posed Comparison With Other Pediatric Excimer Laser
was whether correction using the excimer laser was safe.
The answer to this question also is yes, when safety is Although few studies have described longer-term out- gauged as a low prevalence of loss of vision and a low comes of excimer laser surgery in children, the results of prevalence of sight-threatening complications. No chil- these studies are comparable with those reported dren in our series lost vision, and none of the children summarizes the results of recent reports for com- suffered a devastating corneal complication. The negligi- parison with our findings (the list is representative but not exhaustive). Three of the 5 studies were prospective: Astle gains in “functional vision,” which included balance, awareness of the environment, and coordination. A total of other 2 were retrospective. Autrate and Rehurek reported 64% of the children in the Astle et al study benefited from a cohort of children in 2003 and 2004, and, therefore, the a functional vision improvement, with the most impressive data of the more recent report are The previ- improvements in children with neurobehavioral disorders.
ous studies listed in the Table have taken place at sites We conclude that PRK and LASEK are effective and safe techniques for improving vision in children with my- Surgery was performed under brief general anesthesia opic anisometropia or high bilateral myopia. Appropriate in all studies involving younger children and/or those with cautions should be taken when recommending this form of neurobehavioral disorders. Follow-up ranged from 1 to refractive correction. The main beneficiaries may prove to 2.4 years, and the prevalence of sight-threatening or other be the hard cases, that is, children with severe neurobe- major complications in all of the studies was zero. Simi- havioral disorders. The benefit of the surgery will be larly, the prevalence of haze exceeding 2ϩ was uniformly considerably enhanced if effective methods can be found low. The 4 studies performed outside the United States noted healing of the corneal surface within days aftersurgery but did not quantify healing rate or level of dis- References
comfort. Paysse et reported detailed information on 1. Romano PE, About aniseikonia and refractive surgery. Binocul Vis time to healing of the epithelium and level of discomfort after PRK. The level of discomfort was low in her study, 2. Rubin ML. Optics for clinicians. Gainesville (FL): TRIAD Scientific and time-to-complete healing (mean 3.5 days) was similar 3. Tychsen L. Binocular vision. In: Hart WM, editor. Adler’s physiol- to that which we report (mean 3.6 days). Paysse et also ogy of the eye: clinical applications. St. Louis (MO): CV Mosby, have reported data on average error of ablation centration in pediatric PRK, which was minor, and equivalent to that 4. Krueger RR, Talamo JH, McDonald MB, Varnell RJ, Wagoner MD, McDonnell PJ. Clinical analysis of excimer laser photorefractive With the exception of Nucci and each of the keratectomy using a multiple zone technique for severe myopia. Am JOphthalmol 1995;119:263-74 studies treated amblyopic children younger than 9 years of 5. Kim JH, Kim MS, Hahn TW, Lee YC, Sah WJ, Park CK. Five year age. The average magnitude of anisometropic correction results of photorefractive keratectomy for myopia. J Cataract Refract was large and comparable across studies, ranging from 6 to 9 D. Gains in acuity were noted in each study. Minimal 6. Hersh PS, Stulting RD Steinert RF, et al. Results of phase III excimer laser photorefractive keratectomy for myopia. The Summit gain was reported by Nucci and Drack, which they note PRK Study Group. Ophthalmology 1997;104:1535-53.
was likely explained by correction at an age beyond which 7. Lee YC, Hu FR, Wang IJ. Quality of vision after laser in situ amblyopia is reversible. The amount of myopic correction keratomileusis: influence of dioptric correction and pupil size on (ϳ9 D), and the mean gain in acuity (0.20) reported in the visual function. J Cataract Refract Surg 2003;29:769-77.
Canadian study of Astle et al. are remarkably similar to 8. Nucci P, Drack AV. Refractive surgery for unilateral high myopia in children. J Am Assoc Pediatr Ophthalmol Strabismus 2001;5:348-51.
those we measured. The largest average gain in acuity is 9. Astle WF, Huang PT, Ells AL, Cox RG, Deschenes MC, Vibert that reported from the Czech Republic by Autrata and HM. Photorefractive keratectomy in children. J Cataract Refract Rehurek: 0.55 or twice that claimed in the 2 North Amer- ican investigations. The reasons for the discrepancy are 10. Autrata R, Rehurek J. Laser-assisted subepithelial keratectomy and not entirely clear but could potentially be explained if photorefractive keratectomy versus conventional treatment of myo-pic anisometropic amblyopia in children. J Cataract Refract Surg adherence to spectacle wear and occlusion therapy were markedly better in the Czech study. (The study did not 11. O’Keefe M, Nolan L. LASIK surgery in children. Br J Ophthalmol report compliance data but does appear to have excluded children with neurobehavioral disorders.) 12. Melki SA, Talamo JH, Demetriades AM, et al. Late traumatic dis- Rates of myopic regression were generally similar location of laser in situ keratomileusis corneal flaps. Ophthalmology2000;107:2136-9.
across the 3 largest (ours included), ranging 13. Patel CK, Hanson R, McDonald B, Cox N. Late dislocation of a from 1.06 to 1.7 D/year. Given the importance of corti- LASIK flap caused by a fingernail. Arch Ophthalmol 2002;119:447- costeroids in reducing regression and haze in adult pa- 448; correction 1565 and 2002;120:180.
we were surprised that no other study recorded 14. Heickell AG, Vesaluoma MH, Tervo TMT, Vannas A, Krootila K.
compliance data for administration of drops (each of the Late traumatic dislocation of laser in situ keratomileusis flaps. JCataract Refract Surg 2004;30:253-6.
five studies used fluorometholone as the drop of choice).
15. Lee JB, Seong JG, Lee JH, Seo KY, Kee YG, Kim EK. Comparison Systemic ascorbate was not used in the previous pediatric of laser epithelial keratomileusis and photorefractive keratectomy for low to moderate myopia. J Cataract Refract Surg 2001;27:565-70.
Postoperative improvement in binocular function was 16. Claringbold II TV. Laser-assisted subepithelial keratectomy for the correction of myopia. J Cataract Refract Surg 2002;28:17-22.
reported by Autrata and Rehurek, with gains exceeding 17. Stojanovic A, Ringvold A, Nitter T. Ascorbate prophylaxis for cor- neal haze after photorefractive keratectomy. J Refract Surg 2003;19: binocular fusion per se but did survey parents to assess Journal of AAPOSVolume 9 Number 3 June 2005 18. Probst LE. The problem with pupils. J Cataract Refract Surg 2004; 0.1% acetate after photorefractive keratectomy. Eur J Ophthalmol 19. Vigo L, Scandola E, Carones F. Scraping and mitomycin C to treat 26. Vetrugno M, Maino A, Quaranta GM, Cardia L. The effect of early haze and regression after photorefractive keratectomy for myopia. J steroid treatment after PRK on clinical and refractive outcomes. Acta 20. Carones F, Vigo L, Scandola E, Vacchini L. Evaluation of the prophy- 27. Kasetsuwan N, Wu FM, Hsieh F, Sanchez D, McDonnell PJ. Effect lactic use of mitomycin-C to inhibit haze formation after photorefrac- of topical ascorbic acid on free radical tissue damage and inflamma- tive keratectomy. J Cataract Refract Surg 2002;28:2088-95.
tory cell influx in the cornea after excimer laser corneal surgery. Arch 21. Marshall J, Trokel SL, Rothery S, Krueger RR. Long-term healing of the central cornea after photorefractive keratectomy suing an 28. Corbett MC, O’Brart DPS, Patmore AL, Marshall J. Effect of excimer laser. Ophthalmology 1988;95:1411-21.
collagenase inhibitors on corneal haze after PRK. Exp Eye Res.
22. Moller-Pedersen T, Cavanagh HD, Petroll WM, Jester JV. Stromal wound healing explains refractive instability and haze development after 29. Autrata R, Rehurek J. Clinical results of excimer laser photorefrac- photorefractive keratectomy. Ophthalmology. 2000;107:1235-45.
23. Goggin M, Foley-Nolan A, Algawi K, O’Keefe M. Regression after tive keratectomy for high myopic anisometropia in children: four- photorefractive keratectomy for myopia. J Cataract Refract Surg year follow-up. J Cataract Refract Surg 2003;29:694-702.
30. Paysse EA, Hamill B, Koch DD, Hussein MAW, McCreery KMB, 24. Phillips AF, Hayashi S, Seitz B, Wee WR, McDonnell PJ. Effect of Coats DK. Epithelial healing and ocular discomfort after photore- diclofenac, ketorolac, and fluorometholone on arachidonic acid me- fractive keratectomy in children. J Cataract Refract Surg 2003;29: tabolites following excimer laser corneal surgery. Arch Ophthalmol 31. Paysse EA, Hussein MAW, Koch DD, et al. Successful implemen- 25. Vetrugno M, Quaranta GM, Maino A, Cardia L. A randomized, tation of a protocol for photorefractive keratectomy in children comparative study of fluorometholone 0.2% and fluorometholone requiring anesthesia. J Cataract Refract Surg 2003;29:1744-7.
An Eye on the Arts – The Arts on the Eye
It was one of those rare times when a bomb could have exploded beside me and I wouldn’t have noticed. I was absorbed in Jim, watching his expressions, listening to hiswords, enjoying the moment. I sat opposite him at a table next to the wall; a candle betweenus, its flame reflected in his eyes.
He noticed my eyes too. “You looked beautiful,” he told me recently, “but obviously I He said he wanted to reach over and touch my face near that scar, a sign of comfort or empathy, but he resisted. That would come later. “You were a person who might have died,a person who even if you had lived had no business sitting beside me having dinner, feedingyourself. So I knew right away you were a survivor.” He smiled. “There’s a sense of fragilityabout you, but scratch below the surface a little bit and you’ll find somebody who won’t betrifled with. I knew right away you were a person who wouldn’t break accidentally. You’dbeen through stuff I doubt I could have made it through. And though I still wanted to touchyou and comfort you, I sensed you were stronger than me.
“The first thing I felt from you was your heart, your warmth,” Jim explained. “Maybe that’s what makes you so strong. Your ability to give your heart to others.” —Trisha Meili (from I Am The Central Park Jogger, Simon & Schuster)

Source: http://www.aiorao.it/forum/Public/Data/Hans/200841723634_Refractive%20surgery%20-%20children.pdf

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ESTRADIOL ------------------------------------------------------------------------------------------------------------------------------------------------------ HAZARD SUMMARY WORKPLACE EXPOSURE LIMITS Estradiol can affect you when breathed in and by passing No occupational exposure limits have been established for Estradiol . This does not mean that this substance is not Contact

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