TITLE: Laser Refractive Surgery in Children: A Review of the Clinical Effectiveness and Guidelines

Transcription

1 TITLE: Laser Refractive Surgery in Children: A Review of the Clinical Effectiveness and Guidelines DATE: 11 March 2010 CONTEXT AND POLICY ISSUES: Amblyopia, commonly referred to as lazy, is a functional reduction in the visual acuity of an caused by disuse during the critical period of visual development. 1 It is one of the most common preventable causes of monocular vision loss in children with an estimated prevalence ranging from 1% to 4% in the United States. 2,3 Anisometropic develops when unequal refractive errors exist between the two s. 1,4 The difference in refraction, as well as the refractive error, causes the image to be out of focus on one retina, diminishing the development of the visual pathway in the amblyopic. 1 There are three types of refractive errors: myopia (nearsightedness), hyperopia (farsightedness), and astigmatism (when the optical system of the, particularly the cornea, is not perfectly spherical). Children with dense superficial opacities of the cornea as a result of post-infectious or post-traumatic scarring are also at risk for developing. 5 The critical period of visual development is thought to span from birth to approximately seven years of age. 6 It is believed that children with or amblyogenic factors should be treated early within this period to achieve optimal visual and functional outcomes. 1 Conventional treatments include spectacle correction, contact lenses, and occlusion therapy with patching or atropine penalization of the better-seeing. 1 However, some children may not respond to these treatments due to aniseikonia (when the image seen by one differs in size or shape from that seen by the other with the use of corrective spectacles), compliance issues, or both. 4 Compliance is worsened when children have concurrent neurobehavioural disorders such as autism, cerebral palsy, developmental delay, Down s syndrome, or other associated ocular disorders (e.g., corneal, retinal, and optic nerve problems). 7 The advent of laser refractive surgery has provided an alternative for the management of in children failing conventional therapy. Laser-assisted in situ keratomileusis (LASIK), photorefractive keratectomy (), and laser epithelial keratomileusis (LASEK) are three surgical techniques that have been studied for the management of in children with Disclaimer: The Health Technology Inquiry Service (HTIS) is an information service for those involved in planning and providing health care in Canada. HTIS responses are based on a limited literature search and are not comprehensive, systematic reviews. The intent is to provide a list of sources and a summary of the best evidence on the topic that CADTH could identify using all reasonable efforts within the time allowed. HTIS responses should be considered along with other types of information and health care considerations. The information included in this response is not intended to replace professional medical advice, nor should it be construed as a recommendation for or against the use of a particular health technology. Readers are also cautioned that a lack of good quality evidence does not necessarily mean a lack of effectiveness particularly in the case of new and emerging health technologies, for which little information can be found, but which may in future prove to be effective. While CADTH has taken care in the preparation of the report to ensure that its contents are accurate, complete and up to date, CADTH does not make any guarantee to that effect. CADTH is not liable for any loss or damages resulting from use of the information in the report. Copyright: This report contains CADTH copyright material. It may be copied and used for non-commercial purposes, provided that attribution is given to CADTH. Links: This report may contain links to other information available on the websites of third parties on the Internet. CADTH does not have control over the content of such sites. Use of third party sites is governed by the owners own terms and conditions.

2 anisometropia. 4 LASIK requires the creation of a corneal stromal flap while and LASEK are surface-ablation procedures. 7 The main goal of laser refractive surgery in children with anisometropia is to reduce the refractive difference between s (measured as the spherical equivalent [SE] refractive error [RE] in diopters [D]). 8 Other outcomes of interest include improvements in visual acuity and stereopsis (the ability to appreciate depth and judge distances). Post-operative occlusion therapy with patching or atropine penalization is still required for the reversal of and many children continue to wear spectacles if residual refractive error exists following surgery. 4 Phototherapeutic keratectomy (PTK) has been used in children with corneal opacities to increase corneal transparency and smooth the cornea surface to prevent the development of. 5 Laser refractive surgery has also been examined for the correction of high bilateral myopia in children who are not suitable for therapy with glasses or contact lenses due to neurobehavioral disorders (including idiopathic developmental delay/mental retardation, progressive childhood encephalopathies, cerebral palsy, autism, Down s syndrome, Angelman syndrome, and seizure disorders). 4,7 In such cases, laser refractive surgery in both s is used to correct the high refractive error. The major drawback of laser refractive surgery in children is refractive regression (return of the refractive error) following surgery. 4 This could be attributed to continued growth and changes in the cornea as it heals after surgery. 4 In addition, the aggressive healing response in children may cause corneal haze and a decrease in vision. 4 and LASEK have be associated with a slower recovery time and higher risk of post-operative pain, refractive regression, and corneal haze. 8 Potential long-term complications associated with LASIK include flap complications (including dislocation or loss causing a permanent decrease in vision), corneal thinning, halos, and glare. 8 This report reviews the evidence for the clinical effectiveness and safety of laser refractive surgery when used for the management of or to correct high bilateral myopia in children. The availability of evidence-based guidelines for the use of laser refractive surgery in children will also be discussed. RESEARCH QUESTIONS: 1. What is the clinical benefit and harm of laser refractive surgery for vision correction in children? 2. What are the guidelines for laser refractive surgery for vision correction in children? METHODS: A limited literature search was conducted on key health technology assessment resources, including PubMed, the Cochrane Library (Issue 1, 2010), University of York Centre for Reviews and Dissemination (CRD) databases, ECRI, EuroScan, international health technology agencies, and a focused Internet search. The search was limited to English language articles published between 2005 and February No filters were applied to limit the retrieval by study type. This search was supplemented by hand searching the bibliographies of selected papers. Laser Refractive Surgery in Children 2

3 SUMMARY OF FINDINGS: Eleven observational studies 5,9-18 evaluating laser refractive surgery in children were identified. No health technology assessments, systematic reviews, meta-analyses, randomized controlled trials, controlled clinical trials, or evidence-based guidelines were identified. Observational studies Anisometropia Nine observational studies 9-17 evaluating laser refractive surgery for the reduction of anisometropia in children not responding to conventional therapy were identified. Results of the observational studies are summarized in Table 1. Mean age ranged from 6.1 years to 10.3 years with the youngest patient being 10 months old. The mean follow-up duration ranged from 12 months to 5.15 years. Most studies used LASEK or and majority of the procedures were performed under general anesthesia. Results in all nine studies indicated that after surgery, the refractive difference between s was sufficient to reduce the risk of. All studies also noted improvements in visual acuity and stereopsis. One case-control study compared outcomes in children with receiving (n=11) with a retrospective cohort of children receiving conventional therapy (n=24). 16 Results showed that the mean final refractive error for both the myopic and hyperopic groups was statistically significantly better than that of the control group (p=0.007 and p< , respectively). However, improvements in visual acuity were only noted when children in the group were compared to noncompliant children in the control group. Improvements in visual acuity were not apparent when children in the group were compared with compliant children in the control group. Furthermore, compliance with occlusion therapy did not improve following in any of the patients. 16 Although compliance was not directly measured, another study reported that patients seemed more willing to wear glasses for correction of the residual refractive error following LASIK and aniseikonia was reduced in the majority of the children. 15 No other studies commented on compliance with therapy following laser refractive surgery. Many of the studies observed mild to moderate refractive regression during the follow-up period regardless of the procedure. 10,12,14-17 In one study, a repeat procedure was required in 43% of patients due to significant myopic regression during the two years following or LASEK. 12 The only post-operative complication reported in most studies was visually insignificant haze that later resolved. One study reported significant haze in 8% of s following LASEK or. 17 No relationship between the surgical technique used and the subsequent development of haze was found (ANOVA, p=0.363). However, the severity of haze correlated weakly but significantly with the amount of laser correction (r=0.157; p<0.0001) and younger age at surgery (r=0.115; p<0.001). The authors noted that receiving both topical corticosteroids and oral vitamin C for at least 6 months after surgery reduced regression and haze. 17 The same trial reported that 5.7% of children required oral analgesic for discomfort within 24 hours of the procedure. No other studies commented on post-operative discomfort or recovery. There were no reports of vision loss or other severe post-operative complications such as halos, glare, infection, or flap dislocation. Laser Refractive Surgery in Children 3

4 Table 1: Studies of Laser Refractive Surgery in Children with Anisometropic Amblyopia Study, Year Astle et al., Design Retrospective (n=47; 72 s) Overall mean age: yrs (range: 10 mos to 17.5 only subgroup (n=10; 18 s) 8.53 yrs (range: 10 mos to 16.0 Procedure, Indication LASEK Bilateral hyperopia with or without hyperopic Pre-Operative Findings Overall (range: 0.00 to ) (range: to +7.75) Post-Operative Results at Last Follow-up Overall Mean SE RE(D): (range: to +2.00) (range: 0.00 to ) 15/18 (83%) s within 1D of fellow Adverse Effects and Complications 3 (6.4%) patients had ring haze outside the visual axis which cleared within 4 months. No reports of significant haze or vision loss. Follow-up: 1 yr 17/18 (94%) s within 2D of fellow Lin et al., Retrospective (n=24; 24 s) yrs (range: 5 to 14 Mean follow-up: mos (range: 18.5 to 74.2 mos) LASIK (n=19) (n=5) (range: to +3.00) (range: to +9.75) (range: to +1.25) (p<0.01 versus preop) 12/19 (63.2%) s within 1D of fellow 14/19 (73.7%) s within 2D of fellow 1 (4.2%) patient developed focal opacity along the edge of the corneal flap with no effect on vision. No ocular complications occurred (range: to +4.13) (p<0.01 versus preop) Laser Refractive Surgery in Children 4

5 Study, Year Design Procedure, Indication Pre-Operative Findings Post-Operative Results at Last Follow-up 3/5 (60%) s within 3D of fellow Adverse Effects and Complications Utine et al., Prospective (n=32; 32 s) yrs (4 to 15 Mean follow-up mos (range: 12 to 60 mos) LASIK Mean manifest SE refraction(d): Mean manifest SE refraction(d): (p<0.01 versus preop) 6/32 (18.8%) s within 0.5D of fellow 15/32 (46.9%) s within 1D of fellow No halos, glare, or intraoperative flap complications observed. Haze formation (severity not reported) in 10 (3.1%) patients. 23/32 (71.9%) s within 2D of fellow 31/32 (96.9%) s within 3D of fellow Astle et al., Retrospective (n=39; 56 s) 6.5 yrs (range: 1.0 to 17.4 Mean follow-up: 5.15 yrs (range: 3.5 to 7.8 (n=19; 29 s) or LASEK (n=20; 27 s) Bilateral myopia and myopic Overall (range: to +1.75) (range: to +1.75) LASEK (range: to +1.50) Overall (range: to +2.25) 25/56 (44.6%) s within 1D of fellow 37/56 (66.1%) s within 2D of fellow 43/56 (76.8%) s within 3D of fellow Trace corneal haze was observed in 6 (31.6%) treated and 3 (15%) LASEK treated patients. All cases resolved (range: to +2.25) Laser Refractive Surgery in Children 5

6 Study, Year Design Procedure, Indication Pre-Operative Findings Post-Operative Results at Last Follow-up LASEK (range: to +1.50) Adverse Effects and Complications Magli et al., Retrospective (n=18; 18 s) 10.1 yrs (range: 7 to 17 Mean follow-up: 39 mos (range 18 to 65 mos) Mean SE RE(D): (range: to ) Mean SE RE(D): (range: to 0.00) (p<0.001 versus preop) No intraoperative complications or infections developed. 3 (16.7%) patients developed trace corneal haze that resolved 6 months after the procedure. Astle et al., Retrospective (n=53; 53 s) 8.4 yrs (range: 10 mos to 16 Follow-up: 1 year LASEK (n=31) (n=3) Astigmatic (n=19) Mean interocular SE RE (D): 9.48 (range: 3.50 to 23.00) Mean interocular SE RE (D): 5.50 (range: 4.75 to 7.00) Astigmatic Mean interocular SE RE (D): 3.13 (range: 1.75 to 5.50) Mean interocular SE RE (D): 2.43 (range: 0.00 to 8.00) Mean interocular SE RE (D): 2.33 (range: 0.75 to 4.37) Astigmatic Mean interocular SE RE (D): 0.74 (range: 0.00 to 3.50) Overall 54% of all s within 1D of fellow No vision loss reported. Haze NR 68% of all s within 2D of fellow 80% of all s within 3D of fellow Laser Refractive Surgery in Children 6

7 Study, Year Design Yin et al., Prospective (n=74; 74 s) yrs (range: 6 to 14 Follow-up: 3 yrs Procedure, Indication LASIK (n=32) (n=42) Pre-Operative Findings (range: to ) (range: to +7.75) Post-Operative Results at Last Follow-up (p<0.01 versus preop) (p<0.01 versus preop) Adverse Effects and Complications Trace haze in 6 (8.1%) patients resolved 6 months after surgery. Paysee et al., Case-control (retrospectively derived cohort) (n=35; 35 s) 6.1 yrs (range: 2 to 11 Mean follow-up: mos versus Conventional Therapy ( n=8; control n=9) ( n=3; control n=15) Mean SE RE(D): Mean SE RE(D): /8 (25%) s within 1D of fellow 5/8 (62.5%) s within 2D of fellow Conventional (p= versus ) Trace haze in 6 (54.5%) patients at last post-operative visit. No clinically significant corneal haze observed at 3- year follow-up /3 (33.3%) s within 1D of fellow 2/3 (66.7%) s within 2D of fellow Conventional Laser Refractive Surgery in Children 7

8 Study, Year Design Procedure, Indication Pre-Operative Findings Post-Operative Results at Last Follow-up (p< versus ) Adverse Effects and Complications Tychsen et al., Prospective (n=35; 36 s) 8.4 yrs (range: 4 to 16 Mean follow-up: 29.2 mos (range: 4 to 42 mos) LASEK (n=18) or (n=17) 25/35 (71.4%) children had a neurobehavioural disorder (range: to ) -3.0 (range: to +4.00) 31/35 (88.6%) children corrected within 1D of goal refraction 4/35 (11.4%) children corrected within 2D of goal refraction No substantial differences were observed in versus LASEKtreated children D=diopters; LASEK=laser epithelial keratomileusis; LASIK=laser-assisted in situ keratomileusis; mos=months; NR=not reported; =photorefractive keratectomy; RE=refractive error; SE=spherical equivalent; yrs=years Corneal Opacities 2 (5.7%) children required oral analgesic for discomfort within 24 hours after the procedure but not thereafter. Trace haze in 28 (78%) s Mild haze in 5 (14%) s Moderate to dense opacity haze in 3 (8%) s. No reports of vision loss Kollias et al. reported the efficacy of PTK for decreasing the risk of in a small series of five children (five s) aged 6 to 8 years with severe corneal scarring. 5 PTK was performed under general anesthesia and refractive and visual outcomes were evaluated. Following surgery, corneal opacities were successfully removed and smoothing of the surface was achieved in all children. Post-operative pain and discomfort were well tolerated by all patients and symptoms such as fatigue, conjunctiva irritation, and photophobia improved. After a mean follow-up of months (range 10 to 41 months) visual acuity improved in four s and correction of refractive error after treatment was possible. Refractive regression was observed in three out of five s. No signs of infection or haze were noted. High Bilateral Myopia with Neurobehavioural Disorders Tychsen et al. evaluated the efficacy of LASEK in a prospective case series of nine children (18 s) with high bilateral myopia and neurobehavioural disorders who were noncompliant with glasses and not candidates for correction with contact lenses. 18 The mean age was 10.2 years (range 3 to 16 years). Preoperative SE ranged from D to 11.5 D. Correction was achieved by bilateral LASEK performed under general anesthesia. After a mean follow-up of 17 months (range 6 to 36 months), post-operative SE ranged from -4.0 D to +2.5 D. Sixteen of 18 s Laser Refractive Surgery in Children 8

9 (88.9%) were corrected to within 1 D of the goal refraction and visual acuity improved in all nine children. Eight (88.9%) children appeared to have enhanced visual awareness, attentiveness and social interactions. regression averaged 0.8 D per year during the follow-up period. Mild corneal haze was observed in 6 (35%) s but none of the children complained of glare, halos, or other subjective visual disturbances after surgery. Limitations No randomized controlled trials have been published on the use of refractive laser surgery in children. Several observational trials were identified but most had sample sizes of less than 50 and follow-up durations ranging from one to eight years. Observational studies are subject to selection bias and studies in a larger number of patients over a longer period of time are needed for the detection of rare complications. There is no clear evidence to support which laser surgery technique (LASEK, LASIK, or /PTK) is optimal to use for different indications in children in terms of clinical effectiveness, post-operative discomfort, and complications. As a result, there are no evidence-based guidelines for the use of laser refractive surgery in children. Most trials did not measure if compliance with occlusion therapy improved following surgery and did not control for prior or ongoing traditional therapy. It is therefore not yet possible to ascertain whether refractive surgery improves treatment outcomes. CONCLUSIONS AND IMPLICATIONS FOR DECISION OR POLICY MAKING: Results from observational trials indicate that laser refractive surgery with LASIK,, and LASEK is effective in reducing anisometropia and improving visual acuity and stereopsis in children resistant to conventional therapy. One case-control study suggested that laser refractive surgery is effective for improving visual acuity only when compared to children who are noncompliant with conventional therapy. The same study showed that surgical reduction of anisometropia did not appear to facilitate post-operative management with occlusion therapy. One study showed that PTK is effective in reducing the risk of in children with corneal opacities. Most studies reported visually insignificant corneal haze in a minority of patients that later resolved. Refractive regression during the follow-up period was common and one study reported the requirement for repeat surgery. Results from one study indicated that bilateral LASEK is effective for improving functional vision in neurobehaviorally-impaired children who have high myopia and are noncompliant with glasses. However, post-operative myopic regression was common. In summary, although results are promising, evidence is limited for the use of laser refractive surgery in children and no evidence-based guidelines were identified. Several clinical effectiveness, safety, and logistic issues need to be addressed. Large long-term controlled trials are needed to support the low complication rate observed in published observational trials. More research is needed to compare the risks and benefits of the different laser surgery techniques in the pediatric population. The long-term requirement for repeat surgery due to refractive regression needs to be examined. Although promising results were achieved for a wide age range of patients, the earliest age to use laser refractive surgery for optimal management has not yet been established. Some authors recommend treating children during the neuroplastic years (before the age of 7 years), when the possibility of reversing the Laser Refractive Surgery in Children 9

10 is greatest. 1,4 However, uncertainty remains concerning the age at which treatment of or its risk factors is most effective. 6 Issues surrounding refractive instability (due to ocular growth after treatment) and a more aggressive immune response in younger children may favor older age at treatment. 1,4 The need for general anesthesia also presents several issues. Inhalational anesthetic agents can affect the function of the laser. 4 The inability of the patient to keep the s centered during surgery may affect the accuracy of the results. 4 Finally, many outpatient surgery centers where laser treatments are performed do not fulfill the requirements necessary for general anesthesia administration. 4,8 Until further information is available, the use of laser refractive surgery in children should take into account the limited experience of these procedures in this population and the benefits versus the risks for the specific patient case. PREPARED BY: Health Technology Inquiry Service htis@cadth.ca Tel: Laser Refractive Surgery in Children 10

11 REFERENCES: 1. Doshi NR, Rodriguez ML. Amblyopia. Am Fam Physician Feb 1;75(3): U.S.Preventive Services Task Force. Screening for visual impairment in children younger than age 5 years: update of the evidence from randomized controlled trials, [Internet]. Rockville (MD): Agency for Healthcare Research and Quality; 2004 May. [cited 2010 Mar 5]. Available from: 3. National Eye Institute [Internet]. Bethesda (MD): U.S. National Institutes of Health; Amblyopia; 2010 [cited 2010 Mar 5]. Available from: 4. Daoud YJ, Hutchinson A, Wallace DK, Song J, Kim T. Refractive surgery in children: treatment options, outcomes, and controversies. Am J Ophthalmol Apr;147(4): Kollias AN, Spitzlberger GM, Thurau S, Grüterich M, Lackerbauer CA. Phototherapeutic keratectomy in children. Journal of Refractive Surgery Sep;23(7): Schmucker C, Kleijnen J, Grosselfinger R, Riemsma R, Antes G, Lange S, et al. Effectiveness of early in comparison to late(r) treatment in children with or its risk factors: a systematic review. Ophthalmic Epidemiol Jan;17(1): Tychsen L. Refractive surgery for children: excimer laser, phakic intraocular lens, and clear lens extraction. Curr Opin Ophthalmol Jul;19(4): O'Keefe M, Kirwan C. Pediatric refractive surgery. J Pediatr Ophthalmol Strabismus Nov;43(6): Astle WF, Huang PT, Ereifej I, Paszuk A. Laser-assisted subepithelial keratectomy for bilateral hyperopia and hyperopic in children One-year outcomes. J Cataract Refract Surg Feb;36(2): Lin XM, Yan XH, Wang Z, Yang B, Chen QW, Su JA, et al. Long-term efficacy of excimer laser in situ keratomileusis in the management of children with high. Chin Med J (Engl) [Internet] Apr 5 [cited 2010 Feb 18];122(7): Available from: Utine CA, Cakir H, Egemenoglu A, Perente I. LASIK in children with hyperopic. Journal of Refractive Surgery May;24(5): Astle WF, Fawcett SL, Huang PT, Alewenah O, Ingram A. Long-term outcomes of photorefractive keratectomy and laser-assisted subepithelial keratectomy in children. J Cataract Refract Surg Mar;34(3): Magli A, Iovine A, Gagliardi V, Fimiani F, Nucci P. Photorefractive keratectomy for myopic anisometropia: a retrospective study on 18 children. Eur J Ophthalmol Sep;18(5): Laser Refractive Surgery in Children 11

12 14. Astle WF, Rahmat J, Ingram AD, Huang PT. Laser-assisted subepithelial keratectomy for in children: outcomes at 1 year. J Cataract Refract Surg Dec;33(12): Yin ZQ, Wang H, Yu T, Ren Q, Chen L. Facilitation of management by laser in situ keratomileusis in high hyperopic and myopic children. J AAPOS Dec;11(6): Paysse EA, Coats DK, Hussein MA, Hamill MB, Koch DD. Long-term outcomes of photorefractive keratectomy for in children. Ophthalmology Feb;113(2): Tychsen L, Packwood E, Berdy G. Correction of large amblyopiogenic refractive errors in children using the excimer laser. J AAPOS Jun;9(3): Tychsen L, Hoekel J. Refractive surgery for high bilateral myopia in children with neurobehavioral disorders: 2. Laser-assisted subepithelial keratectomy (LASEK). J AAPOS Aug;10(4): Laser Refractive Surgery in Children 12