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Pediatric refractive surgery: Corneal and intraocular techniques and beyond
AAPOS Workshop Pediatric refractive surgery: Corneal and intraocular techniques and beyond Evelyn A. Paysse, MD,a Lawrence Tychsen, MD,b and Erin Stahl, MDc SUMMARY
Refractive surgery has now been used successfully to treat severe anisometropia and isoametropia associated with amblyopia in children who cannot wear standard spectacles or contact lenses. Extraocular techniques include photorefractive keratectomy, laserassisted subepithelial keratomileusis, and laser-assisted in situ keratomileusis. Intraocular techniques include refractive lensectomy and phakic intraocular lenses and are still being investigated in children for refractive errors outside the treatment dose capabilities of the excimer laser. This workshop discusses the various techniques, how and when to use each, and their risks and benefits. Newer techniques currently being used in adults that may someday be used in children are also introduced. ( J AAPOS 2012;16:291-297)
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xcimer laser surgery for high refractive error associated with amblyopia has been reported in the published literature with good visual acuity and refractive results and minimal complications for over 15 years.1-25 Intraocular refractive procedures have been reported for up to 7 years in the published literature, albeit in smaller numbers for higher refractive errors, also with good visual and refractive outcomes and few complications.26-32 Although refractive surgery has been shown to be effective for improving vision and reducing refractive error in children, it is important to remember that it is appropriate only in special circumstances for a few pediatric subpopulations. This workshop discusses appropriate populations to consider for refractive surgery, eligibility criteria, the “nuts and bolts” of setting up a pediatric refractive surgery center, extraocular and intraocular techniques for normalizing refractive error in children, and newer technology that may prove useful in children in the future. Conventional amblyopia therapy consists of the following steps: (1) clearing the ocular media if there is a visual obstruction such as a leukoma, visually significant cataract, or vitreous hemorrhage; (2) correcting significant refractive error with either spectacles or contact lenses; and (3) occlusion or pharmacologic and/or optical penalization of the fellow eye.33-35 These conventional therapies are successful in the majority of children with amblyopia. Author affiliations: aBaylor College of Medicine, Texas Children’s Hospital, Houston, Texas; b St. Louis Children’s Hospital, Washington University Medical Center, St. Louis, Missouri; c Children’s Mercy Hospital, University of Missouri–Kansas City, Kansas City, Missouri Submitted May 31, 2011. Revision accepted January 29, 2012. Correspondence: Evelyn A. Paysse, MD, Texas Children’s Hospital, 6701 Fannin St, MC 640.00, Houston, TX (email: [email protected]). Copyright Ó 2012 by the American Association for Pediatric Ophthalmology and Strabismus. 1091-8531/$36.00 doi:10.1016/j.jaapos.2012.01.012
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There are, however, several subsets of the pediatric population in which conventional therapies are often ineffective, as follows: Children with high-magnitude isoametropia who are spectacle noncompliant or intolerant. These children typically have neurobehavioral abnormalities related to genetic mutations, autism, cerebral palsy, or prematurity. Children with severe anisometropia who are noncompliant or intolerant of spectacle and contact lens wear. Children with high ametropia, either anisometropia or isoametropia, who have other special circumstances, such as craniofacial anomalies, ear deformities, or neck hypotonia that preclude the use of refractive correction. In the past, no other treatment options existed for these patients, resulting in varying levels of visual impairment and, with continued lack of treatment, degradation of functional vision (uncorrected visual acuity) up to 20/3400 (ie, counting fingers) in the affected eye(s),30 tantamount to functional blindness in bilateral cases. Children with high levels of uncorrected refractive error unnecessarily exist within a cocoon of visual isolation where visual stimuli are noxious and frightening. This often leads to or compounds antisocial behavior, lack of interest, and behavioral difficulties. Refractive surgery can normalize refractive error in these children. The resulting improvement in visual acuity in bilaterally affected children improves their developmental quotient and social skills16 (Paysse EA, Gonzalez-Diaz M, Wang D, Turcich MR, Hager J, Coats DK. Developmental improvement in children with neurobehavioral disorders following photorefractive keratectomy for bilateral high-refractive error. J AAPOS 2011;15:e6 [Abstract 022]). Untreated severe refractive error in young children can also result in severe amblyopia akin to deprivation amblyopia occurring with dense congenital cataract or leukoma. This form of amblyopia must be treated in the same way we
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approach other causes of vision deprivation: by offering a surgical procedure that treats the cause of the vision deprivation, namely, refractive surgery. Surgery can treat high refractive error and it appears to be safe at medium-term follow-up (10 years); it is thus an appropriate treatment for these conditions when standard therapy fails and the alternative will be certain functional blindness in the affected eye(s). Refractive surgery in the future may even be used to prevent refractive amblyopia.
Types of Refractive Surgery Used in Children To the lay public, refractive surgery is synonymous with LASIK (laser in situ keratomileusis) surgery. For the refractive surgeon, the surgical devices and techniques available for improving uncorrected vision are many, and new technology is being developed and investigated at a rapid pace. The refractive surgeon’s current armamentarium includes lasers, corneal inlays, microwave devices, biochemical manipulation, and intraocular lenses. Refractive surgery has been evolving since 1950, when Jose Barraquer developed an instrument to create a corneal flap to correct refractive error. Radial keratotomy, epikeratophakia, and hexagonal keratotomy followed— techniques that have been supplanted by the introduction of laser technology. Excimer laser was first proposed for the treatment of corneal refractive errors by Stephen Trokel in 1983. Laser technology evolved rapidly and photorefractive keratectomy (PRK) was first performed on humans in the mid-1980s by Theo Seiler. As a melding of PRK and Dr. Barraquer’s early thoughts on keratomileusis, LASIK was first performed in 1990 by Lucio Burrato and Ioannis Pallikaris. Today, extraocular laser procedures are performed by the excimer laser and include PRK and laser-assisted subepithelial keratectomy (LASEK), henceforth referred to as advanced surface ablation (ASA) and LASIK. ASA and LASIK have been approved to treat up to 12 D of myopia, 5 D of hyperopia, and 4 D of astigmatism. Extraocular procedures change the corneal power by flattening or steepening the corneal curvature. The intraocular procedures in use today are typically used to treat higher refractive errors that fall outside the treatment parameters for excimer laser or in cases where the cornea is too thin for the safe application of the excimer laser. Phakic intraocular lens (IOL) procedures add or reduce lens power. In the United States, phakic IOLs have been available since 2004 and are only FDA-approved for adults for myopia.36 An IOL is placed into either the anterior or the posterior chamber, with preservation of the natural crystalline lens. The anterior chamber lens available in the United States is the Verisyse lens (Abbott Medical Optics, Santa Ana, CA), the same lens as the Artisan phakic IOL marketed in Europe and Asia. This phakic IOL can be used to treat severe high myopia if the anterior chamber is deep enough to tolerate the lens (minimum 3.2 mm).
Volume 16 Number 3 / June 2012 Hyperopic phakic IOLs are available by special request and are distributed by Ophthtec (Boca Raton, FL, by special request); the same anterior chamber depth requirements hold. The posterior chamber lens that is available in the United States is the Visian ICL (Staar Surgical, Monrovia, CA). No minimum anterior chamber depth is required for this lens. The other procedure in use today that changes lens power is refractive lens exchange, also known as clear lens extraction. In this procedure, the noncataractous natural lens is removed with or without IOL placement as a refractive procedure. Currently, both excimer and intraocular refractive procedures are utilized off-label in children.
Procedures Photorefractive Keratectomy We prefer ASA to LASIK because it has a lower risk profile (Table 1). The main risk of ASA is corneal haze, which occurs infrequently if the proper postoperative regimen is followed. Our procedure for PRK from induction to anesthesia recovery is as follows: general anesthesia can be induced either in a separate induction room or in the same room as the laser. An intravenous line is placed after the child is asleep, and a laryngeal mask airway is inserted into the posterior pharynx. If the child was induced in a separate induction room, then he is transported to the adjacent operating room fully monitored. In the operating room, the laryngeal mask is connected to a standard semiclosed circle system through which the patient receives inhalational anesthesia per the anesthesiologist. Propofol may also be used if desired. Once the child is anesthetized, an examination under anesthesia is performed to reconfirm pachymetry, keratometry, axial length, and intraocular pressure. A slit-lamp examination and a nondilated fundus examination are also performed. The PRK is then performed as follows. The child’s head is first fixated in the desired position with a pneumatic pillow so that the orbital rim is orthogonal to the axis of the laser. The surgeon fixates the eye with forceps to position the plane of the iris perpendicular to the laser beam, taking care to avoid globe/corneal distortion. The laser aiming beam is centered on the entrance pupil. The central cornea is marked to 9 mm using a corneal marker, and the epithelium is removed manually or with an automated rotary brush. The desired refractive correction is programmed into the excimer laser machine. Autotracking is employed to negate minor head oscillations due to respiration, and the laser procedure is performed. Topical nonsteroidal anti-inflammatory drug and fourth-generation fluoroquinolone and fluorometholone 0.1% are placed in the treated eye and a disposable contact lens is placed on the cornea. A transparent shield is then taped over the operated eye(s). Goggles can be used instead. Immediate postoperative medications include topical moxifloxicin and fluorometholone (0.1%) four times daily in the treated eye(s). Topical ketorolac can be used up to four times a day as needed
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Table 1. Refractive surgery techniques Procedure
Features
ASA
Excimer surface ablation
LASIK
Excimer stromal ablation
PhIOL
Anterior chamber or posterior chamber phakic intraocular lens Procedure is identical to cataract surgery except the crystalline lens is not cataractous. The purpose is to insert a properly powered intraocular lens.
RLE
Refractive correction range Myopia: up to 12 D Hyperopia: up to 5 D Astigmatism: up to 4 D Same as ASA
Unlimited Unlimited
Risks Corneal haze, Regression of treatment effect, Keratectasia (extremely rare) Regression of treatment effect, epithelial ingrowth, keratectasia (more common than with ASA), flap problems (loss, striae, debris under flap, free flap, decentered flap), diffuse lamellar keratitis, dry eye Endophthalmitis, corneal endothelial cell loss, glaucoma, pigment dispersion, cataract Endophthalmitis, corneal endothelial cell loss, glaucoma, pigment dispersion, retinal detachment
ASA, advanced surface ablation; LASIK, laser-assisted in situ keratomileusis; PhIOL, phakic intraocular lens; RLE, refractive lens exchange.
for discomfort for the first two postoperative days. Oral vitamin C (500 mg) once a day is also prescribed.37 Oral acetaminophen, ibuprofen, or narcotic can also be used for postoperative discomfort. After 1 week, the bandage contact lens is removed and the child is maintained on fluorometholone (0.1%) four times a day for 6 months and the same dose of oral vitamin C for 1 year. The other medications are discontinued. The postoperative follow-up schedule at our institutions is at a minimum at 5-7 days, 1 month, 2-3 months, 6 months, 12 months, and then yearly thereafter. If amblyopia therapy is continued, follow-up may be more frequent as indicated. Safety of ASA versus LASIK Although LASIK has been shown to be effective in children to correct refractive error, ASA has several advantages. The main advantage of ASA over LASIK is that no corneal flap is created; thus, there is no risk of flap loss, epithelial in-growth, or flap striae, which may occur with LASIK. Also, because ASA is performed on the surface of the cornea, the posterior stromal bed remains thicker, with less risk of keratectasia, an important consideration because most children that need treatment with excimer laser procedures require a large treatment dose. Fortunately, there have been no reported cases to date of keratectasia following PRK in children. The main long-term risk of ASA is corneal haze. In our experience, severe corneal haze occurs rarely, typically only when the topical steroid (fluorometholone) was discontinued too early (usually before 5 months postoperatively); topical fluorometholone should be used for 6 months and occasionally longer. Topical mitomycin has been shown to reduce the risk of haze in adults.38 It is being considered in children. The risk of corneal haze can be further controlled by limiting ablation treatments to within the FDA-approved treatment parameters. The other important issue with excimer refractive procedures in general is refractive regression. Regression of treatment effect will occur over the first 6 to 12 months and then
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it usually stabilizes. There may be still some myopic shift over the years, but that may well be due to eye growth. Myopic regression also tends to be more severe with higher excimer treatment doses. Phakic IOL Procedure The implant30 we prefer and that is used most in several reports from other investigators 39-41 is the anterior chamber Artisan iris-enclaved IOL.42-44 As mentioned previously, the myopic Verisyse lens in the United States is the same lens as the Artisan lens marketed in Europe and Asia. Safe insertion and lower long-term risk for loss of corneal endothelial cells require an anterior chamber depth 3.2 mm or greater. A small iridotomy or iridectomy is performed during the procedure to reduce the chance of pupillary block. In cases of high isoametropia, we recommend that the eyes are implanted sequentially, with approximately 1 month elapsing before operation on the second eye.30 Because children’s eyes heal rapidly, a superior clear corneal incision can be employed that achieves the therapeutic effect of a relaxing limbal incision, as most astigmatism in children is with the rule. Preoperative astigmatism may be reduced by about 50%.28,30,45 Absorbable sutures [9-0 polyglactin 910 (Vicryl; Ethicon Inc., Cincinnati, OH)] are used to avoid reanesthetizing the child for suture removal. In some children, arm restraints may be needed for the first postoperative week to prevent eye rubbing. Posterior chamber phakic IOLs have also been implanted in children.26,46,47 Tychsen and colleagues30 provide a detailed description of pediatric phakic IOL implantation. Phakic Intraocular Lens Safety Phakic IOL implantation is not subject to significant refractive regression and may be considered the currently preferred method for surgical correction of pediatric myopia and hyperopia beyond the range of ASA.30,31 Another major advantage is reversibility. The anterior chamber depth required for an iris-enclaved IOL precludes the use
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of this lens in some children. Children who have high lenticular myopia after retinopathy of prematurity may also be unsuitable because they often have shallow chambers (arrested anterior segment growth48). The major concern with the use of any phakic IOL in a child is the longterm effect on the corneal endothelium. Experience to date indicates that endothelial cell loss is low, no greater than that reported in adult implantation.26,29,30,39-41,46,47,49 The data here, however, are meager and accurate endothelial cell counts are difficult to obtain in the children who may benefit most from implantation.30 It is important to note that any refractive surgical procedure, including ASA, phakic IOL, or refractive lens exchange, can be expected to cause some reduction of endothelial cell density. What we currently do not know and need to know is the comparative loss.30 Success with implantation of posterior chamber phakic IOLs in children has also been reported.46 Because these implants lie immediately adjacent to the iris pigment layer and lens, they pose greater risk for pigment dispersion and cataract formation in a pediatric eye.
Refractive Lens Exchange Procedure For children with ametropia exceeding approximately 20 D (the upper limit for phakic IOL power) or anterior chamber depth less than 3.2 mm, a refractive lens exchange procedure is required.28,45 Standard pediatric lensectomy, posterior capsulectomy, and anterior vitrectomy techniques are employed. If emmetropia is to be achieved, a foldable, acrylic IOL (monofocal or multifocal) is implanted, depending on axial length and lens power calculations. A primary capsulectomy/anterior vitrectomy is advisable due to the high rate posterior capsule fibrosis in children’s eyes when the capsule is preserved, just as in pediatric cataract extraction.28 We perform an examination under anesthesia a few months before the planned lensectomy. The peripheral retina is examined in detail by depression. Accurate, immersion axial length measurements are obtained. Tychsen and colleagues28 and Ali and colleagues45 may be consulted for detailed descriptions of refractive lens exchange.
Refractive Lens Exchange Safety Refractive lens exchange is the only option for children with shallow anterior chambers who have refractive error beyond the range of effective ASA treatment.28,45 Removing the natural lens makes accommodation impossible. The major long-term risk of refractive lens exchange is retinal detachment, with an estimated prevalence in adults of 0.26% to 2.2%.50,51 If the axial length exceeds approximately 29 mm, a barrier diode laser therapy can be applied to reduce the risk.52,53 This retinal detachment risk must be weighed against the certainty of blur-induced blindness in the affected eyes if uncorrected.
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Improvements in Visual Acuity and Visual Function Is refractive surgery in children effective? Yes, with a qualification. The relevant measure of effectiveness in children who are completely noncompliant with spectacle or contact lens use is uncorrected visual acuity. Our work, and that of other investigators, shows substantial gains in uncorrected visual acuity using either ASA, LASIK, phakic IOLs, or refractive lens exchange. Impressive gains are also achieved in isoametropic children.1,3,18,28,30 More modest but consistent gains are achieved in the amblyopic eyes of anisometropic children.6,7,9,12-16,18,22,24,54,55 Improvements in best-corrected visual acuity have also been reported.36 The qualification is that one seldom achieves in children the precision commonplace in adult refractive surgery. The goal in pediatric surgery is to prevent blinding levels of refractive amblyopia. In children with isoametropia averaging 7.1 D (and visuomotor comorbidities), treated using ASA, the average gain in uncorrected visual acuity was 13-fold,18 from a mean 20/810 to a mean 20/60. In the subset of these children who would wear glasses during testing, the gain in best-corrected visual acuity was an average twofold. In children with ametropia averaging 15 D (and visuomotor comorbidities) treated by phakic IOL implantation, the average gain in uncorrected visual acuity was 60-fold, from a mean 20/3400 to a mean 20/57.30 The average gain in best-corrected visual acuity was twofold. Similar gains in uncorrected (100-fold) and best-corrected visual acuity have been reported in children with isoametropia, averaging 19 D, treated by refractive lens exchange.28 The majority of reports on pediatric refractive surgery reflect use of ASA to treat anisometropic amblyopia.3,7,8,11-19,22,56,57 There have also been quite a few studies using LASIK, and these also show reliable visual and refractive results.6,7,20,21,24,58 These case series show a reliable response: initial correction of large refractive error to 1.5 D of emmetropia in approximately 90% of treated eyes. The gains in uncorrected or best-corrected visual acuity range from modest to excellent (two to seven lines of improvement), with no reported losses of visual acuity. One half or more of the children treated have improved binocular fusion and stereopsis.12-15,22 Beyond the gains measured in office testing of acuity or binocularity, refractive surgery has also been shown to have positive effects on children’s day-to-day visual function (Paysse EA, et al. Developmental improvement in children with neurobehavioral disorders following photorefractive keratectomy.).30 Enhanced visual awareness, attentiveness, and social interactions have been reported in approximately 80% of children treated for high isoametropia. When measured using Likert-scale visual function questionnaires before and after refractive surgery, scores for eye contact, tracking, observing and reacting, judging depth and distance, and reading improved by an average 73% in isoametropic children and 58% in anisometropic
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Volume 16 Number 3 / June 2012 children (Ghasia FF, Wilson BS, Gordon MO, Brunstrom JE, Tychsen L. Validating a pediatric cerebral palsy visuomotor impairment questionnaire. IOVS 2007;48:ARVO E-Abstract 954).30,59 The developmental quotient, calculated as the mental age divided by the biological age multiplied by 100, has also been shown to improve following PRK in children with neurobehavioral disorders and severe isoametropia (Paysse EA, et al. Developmental improvement in children with neurobehavioral disorders following photorefractive keratectomy.).
Strategy for Pediatric Refractive Surgery The general strategy for children eligible for refractive surgery is as follows. Children with hyperopic isoametropia or anisometropia of 3-6 D or myopic isoametropia or anisometropia of 3-11 D are treated with ASA. Children with refractive errors beyond this range can be treated with a phakic IOL if the anterior chamber depth is 3.2 mm or greater. The remainder of the children can undergo refractive lens exchange. These procedures need to be performed in the majority of cases under general anesthesia.
Refractive Surgery Technologies on the Horizon Since 1990, excimer laser technology has gone through 20 years of maturation. Broad-beam lasers with abrupt transition zones have given way to variable and flyingspot lasers for precise tissue ablation with smooth blend zones. The speed of excimer lasers has increased from several minutes per treatment to as fast as 5-10 seconds. Eye tracking systems have been implemented that allow for exact laser treatments as saccades and gross eye movements can be followed during laser ablation,60 including patients with mild to moderate nystagmus. The original goal for refractive surgery was to move the adult patient with high refractive error being treated with thick glasses or contact lenses to a more functional optical system and a reduced need for this powerful spectacle or contact lens refractive correction. In modern laser refractive surgery, the postoperative goal is vision better than 20/20. To achieve this goal, there have been advances in the laser ablation treatment patterns. Attention has turned to reducing optical aberrations already present in the patient’s optical system and to preventing the creation of new aberrations. To achieve this, new anterior segment and wavefront diagnostic devices have been developed to map the cornea and the entire visual system.61 A further advancement in laser refractive surgery is the transition from manual microkeratomes to femtosecond lasers to make the corneal flap in LASIK surgery. This technology reduces the risks involved in LASIK surgery as flap creation is made safer and more accurate.62 New excimer laser platforms have minor changes in ergonomics, speed, and beam patterns but no significant technology differences. Diagnostic equipment development
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continues to progress and will likely lead to the next advances in laser refractive surgery. In the United States, lasers treatments are programmed to treat based on phoropter measurements or wavefront measurements. New diagnostic capabilities are emerging that can accurately map corneal, epithelial, lens, and whole eye contributions to the error of the optical system.63,64 With these new diagnostic capabilities, future laser ablation patterns can be targeted to correct the specific defects contributing to an individual patient’s refractive error. New technologies are emerging that address cornealand lens-based procedures to correct refractive error and presbyopia. One of the most versatile tools for new refractive procedures is the femtosecond laser. This laser, most commonly used to create LASIK flaps, can be used to cut corneal and intraocular tissues precisely. Proposed corneal procedures include the creation of intrastromal annular incisions to treat presbyopia,65 laser-assisted astigmatic keratotomy incisions for the treatment of astigmatism,66 penetrating cornea incisions for use in refractive lens surgery,67 and the creation of intrastromal pockets for the placement of corneal inlays.68 Lens-based femtosecond procedures include the creation of an anterior or posterior capsulotomy and disassembling the lens nucleus for easy removal by aspiration.69 The femtosecond laser will likely become an essential tool for the comprehensive refractive surgeon. Advances are also being made in other aspects of corneal refractive surgery. A novel technology is the use of microwaves in the peripheral cornea to flatten the central cornea temporarily to treat low myopia.70 This noninvasive procedure could be a safe, office-based treatment for children with low myopia. This treatment is currently being used internationally and will soon be investigated in the United States. As a complement to such temporary treatments, corneal collagen cross-linking may be indicated to “lock-in” the effect. In corneal cross-linking the cornea is saturated with a riboflavin solution and then exposed to ultraviolet light. This treatment increases the stiffness of the cornea by 300%71 and can also be used to stabilize ectatic corneal conditions such as keratoconus, infectious corneal melts, postrefractive ectasia, and pellucid marginal degeneration.71-73 For many patients, corneal refractive surgery is not the ideal procedure to correct their refractive error. In cases of thin corneas, previous surgery, overly steep or flat keratometry, or for refractive errors outside of the range of corneal surgery, lens-based surgery may be a preferred option. New advances in phakic IOLs include foldable lenses that could be inserted through a smaller incision and modification of materials and footplates to make the lenses more tolerable for the angle and corneal endothelium.74 Refractive lens exchange patients may have future options of using accommodative, light adjustable, or bag-filling lens models that allow for accommodation and eliminate the need for glasses to improve near vision.
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As knowledge and use for each of these new technologies increase for the adult population, potential applications for the use in children will arise. Although it is often difficult to navigate the additional challenges of applying adult technology to children, these new technologies may have the potential to address unique needs of young patients and should not be ignored. In conclusion, surgery for children with high refractive error unresponsive to standard therapy appears to be effective at this medium-term follow-up. Interventional case series and case-control studies of excimer laser refractive surgery, phakic IOLs, and refractive lens exchange in children have demonstrated improvements in uncorrected and best-corrected visual acuity, and developmental and social functioning, in addition to reduced refractive error with few complications. The majority of children with either unilateral or bilateral refractive error do well with contact lenses or spectacles, but for the subset of children who do not, refractive surgery is a reasonable surgical alternative and the last option to prevent a lifetime of severe visual impairment. Randomized clinical trials would be helpful to confirm or disprove efficacy.
References 1. Astle WF, Huang PT, Ereifej I, Paszuk A. Laser-assisted subepithelial keratectomy for bilateral hyperopia and hyperopic anisometropic amblyopia in children: One-year outcomes. J Cataract Refract Surg 2010;36:260-67. 2. Paysse EA. Pediatric excimer refractive surgery. Int Ophthalmol Clin 2010;50:95-105. 3. Ali o JL, Artola A, Claramonte P, Ayala MJ, Chipont E. Photorefractive keratectomy for pediatric myopic anisometropia. J Cataract Refract Surg 1998;24:327-30. 4. Autrata R, Reh urek J, Holousova M. [Photorefractive keratectomy in high myopic anisometropia in children]. Cesk Slov Oftalmol 1999;55: 216-21. 5. Haw WW, Alcorn DM, Manche EE. Excimer laser refractive surgery in the pediatric population. J Pediatr Ophthalmol Strabismus 1999; 36:173-7; quiz 206-7. 6. Rashad KM. Laser in situ keratomileusis for myopic anisometropia in children. J Refract Surg 1999;15:429-35. 7. Nassaralla BR, Nassaralla JJ Jr. Laser in situ keratomileusis in children 8 to 15 years old. J Refract Surg 2001;17:519-24. 8. Astle WF, Huang PT, Ells AL, Cox RG, Deschenes MC, Vibert HM. Photorefractive keratectomy in children. J Cataract Refract Surg 2002;28:932-41. 9. 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. 10. Paysse EA, Hamill MB, Koch DD, Hussein MA, Brady McCreery KM, Coats DK. Epithelial healing and ocular discomfort after photorefractive keratectomy in children. J Cataract Refract Surg 2003;29:478-81. 11. Astle WF, Huang PT, Ingram AD, Farran RP. Laser-assisted subepithelial keratectomy in children. J Cataract Refract Surg 2004; 30:2529-35. 12. Autrata R, Rehurek J. Laser-assisted subepithelial keratectomy and photorefractive keratectomy versus conventional treatment of myopic anisometropic amblyopia in children. J Cataract Refract Surg 2004; 30:74-84. 13. Paysse EA. Photorefractive keratectomy for anisometropic amblyopia in children. Trans Am Ophthalmol Soc 2004;102:341-71.
Volume 16 Number 3 / June 2012 14. Paysse EA, Hamill MB, Hussein MA, Koch DD. Photorefractive keratectomy for pediatric anisometropia: Safety and impact on refractive error, visual acuity, and stereopsis. Am J Ophthalmol 2004;138:70-78. 15. Tychsen L, Packwood E, Berdy G. Correction of large amblyopiogenic refractive errors in children using the excimer laser. J AAPOS 2005;9:224-33. 16. Astle WF, Papp A, Huang PT, Ingram A. Refractive laser surgery in children with coexisting medical and ocular pathology. J Cataract Refract Surg 2006;32:103-8. 17. Paysse EA, Coats DK, Hussein MA, Hamill MB, Koch DD. Longterm outcomes of photorefractive keratectomy for anisometropic amblyopia in children. Ophthalmology 2006;113:169-76. 18. Tychsen L, Hoekel J. Refractive surgery for high bilateral myopia in children with neurobehavioral disorders: 2. Laser-assisted subepithelial keratectomy (LASEK). J AAPOS 2006;10:364-70. 19. Astle WF, Rahmat J, Ingram AD, Huang PT. Laser-assisted subepithelial keratectomy for anisometropic amblyopia in children: Outcomes at 1 year. J Cataract Refract Surg 2007;33:2028-34. 20. Wang H, Yin ZQ, Chen L, Ren Q. [Laser in situ keratomileusis for treatment of high hyperopic anisometropia in children]. Zhonghua Yan Ke Za Zhi 2007;43:112-17. 21. Yin ZQ, Wang H, Yu T, Ren Q, Chen L. Facilitation of amblyopia management by laser in situ keratomileusis in high anisometropic hyperopic and myopic children. J AAPOS 2007;11:571-6. 22. Astle WF, Fawcett SL, Huang PT, Alewenah O, Ingram A. Longterm outcomes of photorefractive keratectomy and laser-assisted subepithelial keratectomy in children. J Cataract Refract Surg 2008;34: 411-6. 23. Magli A, Iovine A, Gagliardi V, Fimiani F, Nucci P. Photorefractive keratectomy for myopic anisometropia: A retrospective study on 18 children. Eur J Ophthalmol 2008;18:716-22. 24. Lin XM, Yan XH, Wang Z, et al. Long-term efficacy of excimer laser in situ keratomileusis in the management of children with high anisometropic amblyopia. Chin Med J (Engl) 2009;122:813-17. 25. Tychsen L. Refractive surgery for special needs children. Arch Ophthalmol 2009;127:810-13. 26. Lesueur LC, Arne JL. Phakic intraocular lens to correct high myopic amblyopia in children. J Refract Surg 2002;18:519-23. 27. Pirouzian A, Ip KC. Anterior chamber phakic intraocular lens implantation in children to treat severe anisometropic myopia and amblyopia: 3-year clinical results. J Cataract Refract Surg 2010;36:1486-93. 28. Tychsen L, Packwood E, Hoekel J, Lueder G. Refractive surgery for high bilateral myopia in children with neurobehavioral disorders: 1. Clear lens extraction and refractive lens exchange. J AAPOS 2006; 10:357-63. 29. Tychsen L. Refractive surgery for children: Excimer laser, phakic intraocular lens, and clear lens extraction. Curr Opin Ophthalmol 2008; 19:342-8. 30. Tychsen L, Hoekel J, Ghasia F, Yoon-Huang G. Phakic intraocular lens correction of high ametropia in children with neurobehavioral disorders. J AAPOS 2008;12:282-9. 31. Ali o JL, Toffaha BT, Laria C, Pi~ nero DP. Phakic intraocular lens implantation for treatment of anisometropia and amblyopia in children: 5-year follow-up. J Refract Surg 2011;27:494-501. 32. Pirouzian A, Ip KC, O’Halloran HS. Phakic anterior chamber intraocular lens (Verisyse) implantation in children for treatment of severe ansiometropia myopia and amblyopia: Six-month pilot clincial trial and review of literature. Clin Ophthalmol 2009;3:367-71. 33. Kivlin JD, Flynn JT. Therapy of anisometropic amblyopia. J Pediatr Ophthalmol Strabismus 1981;18:47-56. 34. France TD, France LW. Optical penalization can improve vision after occlusion treatment. J AAPOS 1999;3:341-3. 35. Kaye SB, Chen SI, Price G, et al. Combined optical and atropine penalization for the treatment of strabismic and anisometropic amblyopia. J AAPOS 2002;6:289-93.
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Volume 16 Number 3 / June 2012 36. Huang D, Schallhorn SC, Sugar A, et al. Phakic intraocular lens implantation for the correction of myopia: A report by the American Academy of Ophthalmology. Ophthalmology 2009;116:2244-58. 37. Stojanovic A, Ringvold A, Nitter T. Ascorbate prophylaxis for corneal haze after photorefractive keratectomy. Ref J Refract Surg 2003;19: 338-43. 38. Chen SH, Feng YF, Stojanovic A, Wang QM. Meta-analysis of clinical outcomes comparing surface ablation for correction of myopia with and without 0.02% Mitomycin C. J Refract Surg 2011;27: 530-41. 39. Assil KK, Sturm JM, Chang SH. Verisyse intraocular lens implantation in a child with anisometropic amblyopia: Four-year follow-up. J Cataract Refract Surg 2007;33:1985-6. 40. Chipont EM, Garcia-Hermosa P, Ali o JL. Reversal of myopic anisometropic amblyopia with phakic intraocular lens implantation. J Refract Surg 2001;17:460-62. 41. Saxena R, van Minderhout HM, Luyten GP. Anterior chamber iris-fixated phakic intraocular lens for anisometropic amblyopia. J Cataract Refract Surg 2003;29:835-8. 42. Budo C, Hessloehl JC, Izak M, et al. Multicenter study of the Artisan phakic intraocular lens. J Cataract Refract Surg 2000;26:1163-71. 43. Sanders DR, Brown DC, Martin RG, Shepherd J, Deitz MR, DeLuca M. Implantable contact lens for moderate to high myopia: Phase 1 FDA clinical study with 6 month follow-up. J Cataract Refract Surg 1998;24:607-11. 44. Alexander L, John M, Cobb L, Noblitt R, Barowsky RT. U.S. clinical investigation of the Artisan myopia lens for the correction of high myopia in phakic eyes. Report of the results of phases 1 and 2, and interim phase 3. Optometry 2000;71:630-42. 45. Ali A, Packwood E, Lueder G, Tychsen L. Unilateral lens extraction for high anisometropic myopia in children and adolescents. J AAPOS 2007;11:153-8. 46. BenEzra D, Cohen E, Karshai I. Phakic posterior chamber intraocular lens for the correction of anisometropia and treatment of amblyopia. Am J Ophthalmol 2000;130:292-6. 47. Lesueur LC, Arne JL. Phakic posterior chamber lens implantation in children with high myopia. J Cataract Refract Surg 1999;25:1571-5. 48. Kent D, Pennie F, Laws D, White S, Clark D. The influence of retinopathy of prematurity on ocular growth. Eye (Lond) 2000; 14(Pt 1):23-9. 49. Pirouzian A, Bansal P, O’Halloran H. Phakic IOL in children. Ophthalmology 2007;114:194-5. 50. Ravalico G, Michieli C, Vattovani O, Tognetto D. Retinal detachment after cataract extraction and refractive lens exchange in highly myopic patients. J Cataract Refract Surg 2003;29:39-44. 51. Neuhann IM, Neuhann TF, Heimann H, Schmickler S, Gerl RH, Foerster MH. Retinal detachment after phacoemulsification in high myopia: Analysis of 2356 cases. J Cataract Refract Surg 2008;34: 1644-57. 52. Arne JL. Phakic intraocular lens implantation versus clear lens extraction in highly myopic eyes of 30- to 50-year-old patients. J Cataract Refract Surg 2004;30:2092-6. 53. Lee KH, Lee JH. Long-term results of clear lens extraction for severe myopia. J Cataract Refract Surg 1996;22:1411-5. 54. Paysse EA. Refractive surgery in children: Is it ready for prime time? Am Orthopt J 2007;57:79-88. 55. O’Keefe M, Kirwan C. Pediatric refractive surgery. J Pediatr Ophthalmol Strabismus 2006;43:333-6.
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56. Nano HD Jr, Muzzin S, Irigaray F. Excimer laser photorefractive keratectomy in pediatric patients. J Cataract Refract Surg 1997;23: 736-9. 57. Singh D. Photorefractive keratectomy in pediatric patients. J Cataract Refract Surg 1995;21:630-32. 58. Rybintseva LV, Sheludchenko VM. Effectiveness of laser in situ keratomileusis with the Nidek EC-5000 excimer laser for pediatric correction of spherical anisometropia. J Refract Surg 2001;17:S224-8. 59. Ghasia F, Tychsen L. Utility values for surgical treatment of high refractive errors in children. J AAPOS 2007;11:89. 60. Lee YC. Active eye-tracking improves LASIK results. J Refract Surg 2007;23:581-5. 61. Jabbur NS, Kraft C, Visx Wavefront Study Group. Wavefront-guided laser in situ keratomileusis using the WaveScan system for correction of low to moderate myopia with astigmatism: 6-month results in 277 eyes. J Cataract Refract Surg 2005;31:1493-501. 62. Stonecipher K, Ignacio TS, Stonecipher M. Advances in refractive surgery: Microkeratome and femtosecond laser flap creation in relation to safety, efficacy, predictability, and biomechanical stability. Curr Opin Ophthalmol 2006;17:368-72. 63. Reinstein DZAT, Gobbe M, Silverman RH, Coleman DJ. Epithelial thickness in the normal cornea: Three-dimensional display with Artemis very high-frequency digital ultrasound. J Refract Surg 2008;24: 571-81. 64. Krueger RR, Rocha K. Introduction to wavefront-optimized, wavefront-guided, and topography-guided customized ablation: Fifth year in review. J Refract Surg 2008;24:S417-8. 65. Holzer MP, Mannsfeld A, Ehmer A, Auffarth GU. Early outcomes of INTRACOR femtosecond laser treatment for presbyopia. J Refract Surg 2009;25:855-61. 66. Abbey A, Ide T, Kymionis GD, Yoo SH. Femtosecond laser-assisted astigmatic keratotomy in naturally occurring high astigmatism. Br J Ophthalmol 2009;93:1566-9. 67. Masket S, Sarayba M, Ignacio T, Fram N. Femtosecond laser-assisted cataract incisions: Architectural stability and reproducibility. J Cataract Refract Surg 2010;36:1048-9. 68. Seyeddain O, Riha W, Hohensinn M, Nix G, Dexl AK, Grabner G. Refractive surgical correction of presbyopia with the AcuFocus small aperture corneal inlay: Two-year follow-up. J Refract Surg 2010;26: 707-15. 69. Nagy Z, Takacs A, Filkorn T, Sarayba M. Initial clinical evaluation of an intraocular femtosecond laser in cataract surgery. J Refract Surg 2009;25:1053-60. 70. Barsam A, Patmore A, Muller D, Marshall J. Keratorefractive effect of microwave keratoplasty on human corneas. J Cataract Refract Surg 2010;36:472-6. 71. Wollensak G, Spoerl E, Seiler T. Stress-strain measurements of human and porcine corneas after riboflavin-ultraviolet-A-induced cross-linking. J Cataract Refract Surg 2003;29:1780-85. 72. Iseli HP, Thiel MA, Hafezi F, Kampmeier J, Seiler T. Ultraviolet A/ riboflavin corneal cross-linking for infectious keratitis associated with corneal melts. Cornea 2008;27:590-94. 73. Spadea L. Corneal collagen cross-linking with riboflavin and UVA irradiation in pellucid marginal degeneration. J Refract Surg 2010; 26:375-7. 74. Kohnen T, Klaproth OK. Three-year stability of an angle-supported foldable hydrophobic acrylic phakic intraocular lens evaluated by Scheimpflug photography. J Cataract Refract Surg 2010;36:1120-26.
Refractive surgery has now been used successfully to treat severe anisometropia and isoametropia associated with amblyopia in children who cannot wear standard spectacles or contact lenses. Extraocular techniques include photorefractive keratectomy, laserassisted subepithelial keratomileusis, and laser-assisted in situ keratomileusis. Intraocular techniques include refractive lensectomy and phakic intraocular lenses and are still being investigated in children for refractive errors outside the treatment dose capabilities of the excimer laser. This workshop discusses the various techniques, how and when to use each, and their risks and benefits. Newer techniques currently being used in adults that may someday be used in children are also introduced. ( J AAPOS 2012;16:291-297)
E
xcimer laser surgery for high refractive error associated with amblyopia has been reported in the published literature with good visual acuity and refractive results and minimal complications for over 15 years.1-25 Intraocular refractive procedures have been reported for up to 7 years in the published literature, albeit in smaller numbers for higher refractive errors, also with good visual and refractive outcomes and few complications.26-32 Although refractive surgery has been shown to be effective for improving vision and reducing refractive error in children, it is important to remember that it is appropriate only in special circumstances for a few pediatric subpopulations. This workshop discusses appropriate populations to consider for refractive surgery, eligibility criteria, the “nuts and bolts” of setting up a pediatric refractive surgery center, extraocular and intraocular techniques for normalizing refractive error in children, and newer technology that may prove useful in children in the future. Conventional amblyopia therapy consists of the following steps: (1) clearing the ocular media if there is a visual obstruction such as a leukoma, visually significant cataract, or vitreous hemorrhage; (2) correcting significant refractive error with either spectacles or contact lenses; and (3) occlusion or pharmacologic and/or optical penalization of the fellow eye.33-35 These conventional therapies are successful in the majority of children with amblyopia. Author affiliations: aBaylor College of Medicine, Texas Children’s Hospital, Houston, Texas; b St. Louis Children’s Hospital, Washington University Medical Center, St. Louis, Missouri; c Children’s Mercy Hospital, University of Missouri–Kansas City, Kansas City, Missouri Submitted May 31, 2011. Revision accepted January 29, 2012. Correspondence: Evelyn A. Paysse, MD, Texas Children’s Hospital, 6701 Fannin St, MC 640.00, Houston, TX (email: [email protected]). Copyright Ó 2012 by the American Association for Pediatric Ophthalmology and Strabismus. 1091-8531/$36.00 doi:10.1016/j.jaapos.2012.01.012
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There are, however, several subsets of the pediatric population in which conventional therapies are often ineffective, as follows: Children with high-magnitude isoametropia who are spectacle noncompliant or intolerant. These children typically have neurobehavioral abnormalities related to genetic mutations, autism, cerebral palsy, or prematurity. Children with severe anisometropia who are noncompliant or intolerant of spectacle and contact lens wear. Children with high ametropia, either anisometropia or isoametropia, who have other special circumstances, such as craniofacial anomalies, ear deformities, or neck hypotonia that preclude the use of refractive correction. In the past, no other treatment options existed for these patients, resulting in varying levels of visual impairment and, with continued lack of treatment, degradation of functional vision (uncorrected visual acuity) up to 20/3400 (ie, counting fingers) in the affected eye(s),30 tantamount to functional blindness in bilateral cases. Children with high levels of uncorrected refractive error unnecessarily exist within a cocoon of visual isolation where visual stimuli are noxious and frightening. This often leads to or compounds antisocial behavior, lack of interest, and behavioral difficulties. Refractive surgery can normalize refractive error in these children. The resulting improvement in visual acuity in bilaterally affected children improves their developmental quotient and social skills16 (Paysse EA, Gonzalez-Diaz M, Wang D, Turcich MR, Hager J, Coats DK. Developmental improvement in children with neurobehavioral disorders following photorefractive keratectomy for bilateral high-refractive error. J AAPOS 2011;15:e6 [Abstract 022]). Untreated severe refractive error in young children can also result in severe amblyopia akin to deprivation amblyopia occurring with dense congenital cataract or leukoma. This form of amblyopia must be treated in the same way we
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approach other causes of vision deprivation: by offering a surgical procedure that treats the cause of the vision deprivation, namely, refractive surgery. Surgery can treat high refractive error and it appears to be safe at medium-term follow-up (10 years); it is thus an appropriate treatment for these conditions when standard therapy fails and the alternative will be certain functional blindness in the affected eye(s). Refractive surgery in the future may even be used to prevent refractive amblyopia.
Types of Refractive Surgery Used in Children To the lay public, refractive surgery is synonymous with LASIK (laser in situ keratomileusis) surgery. For the refractive surgeon, the surgical devices and techniques available for improving uncorrected vision are many, and new technology is being developed and investigated at a rapid pace. The refractive surgeon’s current armamentarium includes lasers, corneal inlays, microwave devices, biochemical manipulation, and intraocular lenses. Refractive surgery has been evolving since 1950, when Jose Barraquer developed an instrument to create a corneal flap to correct refractive error. Radial keratotomy, epikeratophakia, and hexagonal keratotomy followed— techniques that have been supplanted by the introduction of laser technology. Excimer laser was first proposed for the treatment of corneal refractive errors by Stephen Trokel in 1983. Laser technology evolved rapidly and photorefractive keratectomy (PRK) was first performed on humans in the mid-1980s by Theo Seiler. As a melding of PRK and Dr. Barraquer’s early thoughts on keratomileusis, LASIK was first performed in 1990 by Lucio Burrato and Ioannis Pallikaris. Today, extraocular laser procedures are performed by the excimer laser and include PRK and laser-assisted subepithelial keratectomy (LASEK), henceforth referred to as advanced surface ablation (ASA) and LASIK. ASA and LASIK have been approved to treat up to 12 D of myopia, 5 D of hyperopia, and 4 D of astigmatism. Extraocular procedures change the corneal power by flattening or steepening the corneal curvature. The intraocular procedures in use today are typically used to treat higher refractive errors that fall outside the treatment parameters for excimer laser or in cases where the cornea is too thin for the safe application of the excimer laser. Phakic intraocular lens (IOL) procedures add or reduce lens power. In the United States, phakic IOLs have been available since 2004 and are only FDA-approved for adults for myopia.36 An IOL is placed into either the anterior or the posterior chamber, with preservation of the natural crystalline lens. The anterior chamber lens available in the United States is the Verisyse lens (Abbott Medical Optics, Santa Ana, CA), the same lens as the Artisan phakic IOL marketed in Europe and Asia. This phakic IOL can be used to treat severe high myopia if the anterior chamber is deep enough to tolerate the lens (minimum 3.2 mm).
Volume 16 Number 3 / June 2012 Hyperopic phakic IOLs are available by special request and are distributed by Ophthtec (Boca Raton, FL, by special request); the same anterior chamber depth requirements hold. The posterior chamber lens that is available in the United States is the Visian ICL (Staar Surgical, Monrovia, CA). No minimum anterior chamber depth is required for this lens. The other procedure in use today that changes lens power is refractive lens exchange, also known as clear lens extraction. In this procedure, the noncataractous natural lens is removed with or without IOL placement as a refractive procedure. Currently, both excimer and intraocular refractive procedures are utilized off-label in children.
Procedures Photorefractive Keratectomy We prefer ASA to LASIK because it has a lower risk profile (Table 1). The main risk of ASA is corneal haze, which occurs infrequently if the proper postoperative regimen is followed. Our procedure for PRK from induction to anesthesia recovery is as follows: general anesthesia can be induced either in a separate induction room or in the same room as the laser. An intravenous line is placed after the child is asleep, and a laryngeal mask airway is inserted into the posterior pharynx. If the child was induced in a separate induction room, then he is transported to the adjacent operating room fully monitored. In the operating room, the laryngeal mask is connected to a standard semiclosed circle system through which the patient receives inhalational anesthesia per the anesthesiologist. Propofol may also be used if desired. Once the child is anesthetized, an examination under anesthesia is performed to reconfirm pachymetry, keratometry, axial length, and intraocular pressure. A slit-lamp examination and a nondilated fundus examination are also performed. The PRK is then performed as follows. The child’s head is first fixated in the desired position with a pneumatic pillow so that the orbital rim is orthogonal to the axis of the laser. The surgeon fixates the eye with forceps to position the plane of the iris perpendicular to the laser beam, taking care to avoid globe/corneal distortion. The laser aiming beam is centered on the entrance pupil. The central cornea is marked to 9 mm using a corneal marker, and the epithelium is removed manually or with an automated rotary brush. The desired refractive correction is programmed into the excimer laser machine. Autotracking is employed to negate minor head oscillations due to respiration, and the laser procedure is performed. Topical nonsteroidal anti-inflammatory drug and fourth-generation fluoroquinolone and fluorometholone 0.1% are placed in the treated eye and a disposable contact lens is placed on the cornea. A transparent shield is then taped over the operated eye(s). Goggles can be used instead. Immediate postoperative medications include topical moxifloxicin and fluorometholone (0.1%) four times daily in the treated eye(s). Topical ketorolac can be used up to four times a day as needed
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Table 1. Refractive surgery techniques Procedure
Features
ASA
Excimer surface ablation
LASIK
Excimer stromal ablation
PhIOL
Anterior chamber or posterior chamber phakic intraocular lens Procedure is identical to cataract surgery except the crystalline lens is not cataractous. The purpose is to insert a properly powered intraocular lens.
RLE
Refractive correction range Myopia: up to 12 D Hyperopia: up to 5 D Astigmatism: up to 4 D Same as ASA
Unlimited Unlimited
Risks Corneal haze, Regression of treatment effect, Keratectasia (extremely rare) Regression of treatment effect, epithelial ingrowth, keratectasia (more common than with ASA), flap problems (loss, striae, debris under flap, free flap, decentered flap), diffuse lamellar keratitis, dry eye Endophthalmitis, corneal endothelial cell loss, glaucoma, pigment dispersion, cataract Endophthalmitis, corneal endothelial cell loss, glaucoma, pigment dispersion, retinal detachment
ASA, advanced surface ablation; LASIK, laser-assisted in situ keratomileusis; PhIOL, phakic intraocular lens; RLE, refractive lens exchange.
for discomfort for the first two postoperative days. Oral vitamin C (500 mg) once a day is also prescribed.37 Oral acetaminophen, ibuprofen, or narcotic can also be used for postoperative discomfort. After 1 week, the bandage contact lens is removed and the child is maintained on fluorometholone (0.1%) four times a day for 6 months and the same dose of oral vitamin C for 1 year. The other medications are discontinued. The postoperative follow-up schedule at our institutions is at a minimum at 5-7 days, 1 month, 2-3 months, 6 months, 12 months, and then yearly thereafter. If amblyopia therapy is continued, follow-up may be more frequent as indicated. Safety of ASA versus LASIK Although LASIK has been shown to be effective in children to correct refractive error, ASA has several advantages. The main advantage of ASA over LASIK is that no corneal flap is created; thus, there is no risk of flap loss, epithelial in-growth, or flap striae, which may occur with LASIK. Also, because ASA is performed on the surface of the cornea, the posterior stromal bed remains thicker, with less risk of keratectasia, an important consideration because most children that need treatment with excimer laser procedures require a large treatment dose. Fortunately, there have been no reported cases to date of keratectasia following PRK in children. The main long-term risk of ASA is corneal haze. In our experience, severe corneal haze occurs rarely, typically only when the topical steroid (fluorometholone) was discontinued too early (usually before 5 months postoperatively); topical fluorometholone should be used for 6 months and occasionally longer. Topical mitomycin has been shown to reduce the risk of haze in adults.38 It is being considered in children. The risk of corneal haze can be further controlled by limiting ablation treatments to within the FDA-approved treatment parameters. The other important issue with excimer refractive procedures in general is refractive regression. Regression of treatment effect will occur over the first 6 to 12 months and then
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it usually stabilizes. There may be still some myopic shift over the years, but that may well be due to eye growth. Myopic regression also tends to be more severe with higher excimer treatment doses. Phakic IOL Procedure The implant30 we prefer and that is used most in several reports from other investigators 39-41 is the anterior chamber Artisan iris-enclaved IOL.42-44 As mentioned previously, the myopic Verisyse lens in the United States is the same lens as the Artisan lens marketed in Europe and Asia. Safe insertion and lower long-term risk for loss of corneal endothelial cells require an anterior chamber depth 3.2 mm or greater. A small iridotomy or iridectomy is performed during the procedure to reduce the chance of pupillary block. In cases of high isoametropia, we recommend that the eyes are implanted sequentially, with approximately 1 month elapsing before operation on the second eye.30 Because children’s eyes heal rapidly, a superior clear corneal incision can be employed that achieves the therapeutic effect of a relaxing limbal incision, as most astigmatism in children is with the rule. Preoperative astigmatism may be reduced by about 50%.28,30,45 Absorbable sutures [9-0 polyglactin 910 (Vicryl; Ethicon Inc., Cincinnati, OH)] are used to avoid reanesthetizing the child for suture removal. In some children, arm restraints may be needed for the first postoperative week to prevent eye rubbing. Posterior chamber phakic IOLs have also been implanted in children.26,46,47 Tychsen and colleagues30 provide a detailed description of pediatric phakic IOL implantation. Phakic Intraocular Lens Safety Phakic IOL implantation is not subject to significant refractive regression and may be considered the currently preferred method for surgical correction of pediatric myopia and hyperopia beyond the range of ASA.30,31 Another major advantage is reversibility. The anterior chamber depth required for an iris-enclaved IOL precludes the use
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of this lens in some children. Children who have high lenticular myopia after retinopathy of prematurity may also be unsuitable because they often have shallow chambers (arrested anterior segment growth48). The major concern with the use of any phakic IOL in a child is the longterm effect on the corneal endothelium. Experience to date indicates that endothelial cell loss is low, no greater than that reported in adult implantation.26,29,30,39-41,46,47,49 The data here, however, are meager and accurate endothelial cell counts are difficult to obtain in the children who may benefit most from implantation.30 It is important to note that any refractive surgical procedure, including ASA, phakic IOL, or refractive lens exchange, can be expected to cause some reduction of endothelial cell density. What we currently do not know and need to know is the comparative loss.30 Success with implantation of posterior chamber phakic IOLs in children has also been reported.46 Because these implants lie immediately adjacent to the iris pigment layer and lens, they pose greater risk for pigment dispersion and cataract formation in a pediatric eye.
Refractive Lens Exchange Procedure For children with ametropia exceeding approximately 20 D (the upper limit for phakic IOL power) or anterior chamber depth less than 3.2 mm, a refractive lens exchange procedure is required.28,45 Standard pediatric lensectomy, posterior capsulectomy, and anterior vitrectomy techniques are employed. If emmetropia is to be achieved, a foldable, acrylic IOL (monofocal or multifocal) is implanted, depending on axial length and lens power calculations. A primary capsulectomy/anterior vitrectomy is advisable due to the high rate posterior capsule fibrosis in children’s eyes when the capsule is preserved, just as in pediatric cataract extraction.28 We perform an examination under anesthesia a few months before the planned lensectomy. The peripheral retina is examined in detail by depression. Accurate, immersion axial length measurements are obtained. Tychsen and colleagues28 and Ali and colleagues45 may be consulted for detailed descriptions of refractive lens exchange.
Refractive Lens Exchange Safety Refractive lens exchange is the only option for children with shallow anterior chambers who have refractive error beyond the range of effective ASA treatment.28,45 Removing the natural lens makes accommodation impossible. The major long-term risk of refractive lens exchange is retinal detachment, with an estimated prevalence in adults of 0.26% to 2.2%.50,51 If the axial length exceeds approximately 29 mm, a barrier diode laser therapy can be applied to reduce the risk.52,53 This retinal detachment risk must be weighed against the certainty of blur-induced blindness in the affected eyes if uncorrected.
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Improvements in Visual Acuity and Visual Function Is refractive surgery in children effective? Yes, with a qualification. The relevant measure of effectiveness in children who are completely noncompliant with spectacle or contact lens use is uncorrected visual acuity. Our work, and that of other investigators, shows substantial gains in uncorrected visual acuity using either ASA, LASIK, phakic IOLs, or refractive lens exchange. Impressive gains are also achieved in isoametropic children.1,3,18,28,30 More modest but consistent gains are achieved in the amblyopic eyes of anisometropic children.6,7,9,12-16,18,22,24,54,55 Improvements in best-corrected visual acuity have also been reported.36 The qualification is that one seldom achieves in children the precision commonplace in adult refractive surgery. The goal in pediatric surgery is to prevent blinding levels of refractive amblyopia. In children with isoametropia averaging 7.1 D (and visuomotor comorbidities), treated using ASA, the average gain in uncorrected visual acuity was 13-fold,18 from a mean 20/810 to a mean 20/60. In the subset of these children who would wear glasses during testing, the gain in best-corrected visual acuity was an average twofold. In children with ametropia averaging 15 D (and visuomotor comorbidities) treated by phakic IOL implantation, the average gain in uncorrected visual acuity was 60-fold, from a mean 20/3400 to a mean 20/57.30 The average gain in best-corrected visual acuity was twofold. Similar gains in uncorrected (100-fold) and best-corrected visual acuity have been reported in children with isoametropia, averaging 19 D, treated by refractive lens exchange.28 The majority of reports on pediatric refractive surgery reflect use of ASA to treat anisometropic amblyopia.3,7,8,11-19,22,56,57 There have also been quite a few studies using LASIK, and these also show reliable visual and refractive results.6,7,20,21,24,58 These case series show a reliable response: initial correction of large refractive error to 1.5 D of emmetropia in approximately 90% of treated eyes. The gains in uncorrected or best-corrected visual acuity range from modest to excellent (two to seven lines of improvement), with no reported losses of visual acuity. One half or more of the children treated have improved binocular fusion and stereopsis.12-15,22 Beyond the gains measured in office testing of acuity or binocularity, refractive surgery has also been shown to have positive effects on children’s day-to-day visual function (Paysse EA, et al. Developmental improvement in children with neurobehavioral disorders following photorefractive keratectomy.).30 Enhanced visual awareness, attentiveness, and social interactions have been reported in approximately 80% of children treated for high isoametropia. When measured using Likert-scale visual function questionnaires before and after refractive surgery, scores for eye contact, tracking, observing and reacting, judging depth and distance, and reading improved by an average 73% in isoametropic children and 58% in anisometropic
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Volume 16 Number 3 / June 2012 children (Ghasia FF, Wilson BS, Gordon MO, Brunstrom JE, Tychsen L. Validating a pediatric cerebral palsy visuomotor impairment questionnaire. IOVS 2007;48:ARVO E-Abstract 954).30,59 The developmental quotient, calculated as the mental age divided by the biological age multiplied by 100, has also been shown to improve following PRK in children with neurobehavioral disorders and severe isoametropia (Paysse EA, et al. Developmental improvement in children with neurobehavioral disorders following photorefractive keratectomy.).
Strategy for Pediatric Refractive Surgery The general strategy for children eligible for refractive surgery is as follows. Children with hyperopic isoametropia or anisometropia of 3-6 D or myopic isoametropia or anisometropia of 3-11 D are treated with ASA. Children with refractive errors beyond this range can be treated with a phakic IOL if the anterior chamber depth is 3.2 mm or greater. The remainder of the children can undergo refractive lens exchange. These procedures need to be performed in the majority of cases under general anesthesia.
Refractive Surgery Technologies on the Horizon Since 1990, excimer laser technology has gone through 20 years of maturation. Broad-beam lasers with abrupt transition zones have given way to variable and flyingspot lasers for precise tissue ablation with smooth blend zones. The speed of excimer lasers has increased from several minutes per treatment to as fast as 5-10 seconds. Eye tracking systems have been implemented that allow for exact laser treatments as saccades and gross eye movements can be followed during laser ablation,60 including patients with mild to moderate nystagmus. The original goal for refractive surgery was to move the adult patient with high refractive error being treated with thick glasses or contact lenses to a more functional optical system and a reduced need for this powerful spectacle or contact lens refractive correction. In modern laser refractive surgery, the postoperative goal is vision better than 20/20. To achieve this goal, there have been advances in the laser ablation treatment patterns. Attention has turned to reducing optical aberrations already present in the patient’s optical system and to preventing the creation of new aberrations. To achieve this, new anterior segment and wavefront diagnostic devices have been developed to map the cornea and the entire visual system.61 A further advancement in laser refractive surgery is the transition from manual microkeratomes to femtosecond lasers to make the corneal flap in LASIK surgery. This technology reduces the risks involved in LASIK surgery as flap creation is made safer and more accurate.62 New excimer laser platforms have minor changes in ergonomics, speed, and beam patterns but no significant technology differences. Diagnostic equipment development
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continues to progress and will likely lead to the next advances in laser refractive surgery. In the United States, lasers treatments are programmed to treat based on phoropter measurements or wavefront measurements. New diagnostic capabilities are emerging that can accurately map corneal, epithelial, lens, and whole eye contributions to the error of the optical system.63,64 With these new diagnostic capabilities, future laser ablation patterns can be targeted to correct the specific defects contributing to an individual patient’s refractive error. New technologies are emerging that address cornealand lens-based procedures to correct refractive error and presbyopia. One of the most versatile tools for new refractive procedures is the femtosecond laser. This laser, most commonly used to create LASIK flaps, can be used to cut corneal and intraocular tissues precisely. Proposed corneal procedures include the creation of intrastromal annular incisions to treat presbyopia,65 laser-assisted astigmatic keratotomy incisions for the treatment of astigmatism,66 penetrating cornea incisions for use in refractive lens surgery,67 and the creation of intrastromal pockets for the placement of corneal inlays.68 Lens-based femtosecond procedures include the creation of an anterior or posterior capsulotomy and disassembling the lens nucleus for easy removal by aspiration.69 The femtosecond laser will likely become an essential tool for the comprehensive refractive surgeon. Advances are also being made in other aspects of corneal refractive surgery. A novel technology is the use of microwaves in the peripheral cornea to flatten the central cornea temporarily to treat low myopia.70 This noninvasive procedure could be a safe, office-based treatment for children with low myopia. This treatment is currently being used internationally and will soon be investigated in the United States. As a complement to such temporary treatments, corneal collagen cross-linking may be indicated to “lock-in” the effect. In corneal cross-linking the cornea is saturated with a riboflavin solution and then exposed to ultraviolet light. This treatment increases the stiffness of the cornea by 300%71 and can also be used to stabilize ectatic corneal conditions such as keratoconus, infectious corneal melts, postrefractive ectasia, and pellucid marginal degeneration.71-73 For many patients, corneal refractive surgery is not the ideal procedure to correct their refractive error. In cases of thin corneas, previous surgery, overly steep or flat keratometry, or for refractive errors outside of the range of corneal surgery, lens-based surgery may be a preferred option. New advances in phakic IOLs include foldable lenses that could be inserted through a smaller incision and modification of materials and footplates to make the lenses more tolerable for the angle and corneal endothelium.74 Refractive lens exchange patients may have future options of using accommodative, light adjustable, or bag-filling lens models that allow for accommodation and eliminate the need for glasses to improve near vision.
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As knowledge and use for each of these new technologies increase for the adult population, potential applications for the use in children will arise. Although it is often difficult to navigate the additional challenges of applying adult technology to children, these new technologies may have the potential to address unique needs of young patients and should not be ignored. In conclusion, surgery for children with high refractive error unresponsive to standard therapy appears to be effective at this medium-term follow-up. Interventional case series and case-control studies of excimer laser refractive surgery, phakic IOLs, and refractive lens exchange in children have demonstrated improvements in uncorrected and best-corrected visual acuity, and developmental and social functioning, in addition to reduced refractive error with few complications. The majority of children with either unilateral or bilateral refractive error do well with contact lenses or spectacles, but for the subset of children who do not, refractive surgery is a reasonable surgical alternative and the last option to prevent a lifetime of severe visual impairment. Randomized clinical trials would be helpful to confirm or disprove efficacy.
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