- Email: [email protected]
Amblyopia Therapy in Children Identified by Photoscreening
Amblyopia Therapy in Children Identified by Photoscreening Ronald G. Teed, MD,1 Christina M. Bui, MD,1 David G. Morrison, MD,1 Robert L. Estes, MD,1 Sean P. Donahue, MD, PhD1,2,3 Purpose: To determine the efficacy of amblyopia treatment in children identified through a community photoscreening program. Design: Case series. Participants: We included 125 children diagnosed with amblyopia after referral from a photoscreening program. Methods: Retrospective chart review of 125 amblyopic children identified by photoscreening and treated in a single academic pediatric ophthalmology group practice. Treatment regimens included spectacles, patching, and/or atropine penalization. Successful treatment was defined as ⱖ3 Snellen line equivalent improvement in visual acuity and/or 20/30 visual acuity in the amblyopic eye in literate children. Successful treatment in initially preliterate children was defined as 20/30 or better visual acuity in the amblyopic eye. Main Outcome Measures: Percentage of successfully treated amblyopic children. Results: Of 901 children evaluated after being referred from photoscreening, 551 had amblyopiogenic risk factors without amblyopia, 185 were diagnosed with amblyopia, and 165 were false positives. Of 185 children with amblyopia, 125 met inclusion criteria for analysis and 78% (97 of 125) were successfully treated. Conclusions: The success rate of amblyopia treatment in children identified through our photoscreening program is high. This study supports the role of photoscreening programs in the prevention of amblyopia-related vision loss. Such early screening may translate to true visual acuity improvement. Financial Disclosure(s): The authors have no proprietary or commercial interest in any of the materials discussed in this article. Ophthalmology 2010;117:159 –162 © 2010 by the American Academy of Ophthalmology.
Amblyopia is the leading cause of monocular vision impairment in young and middle-aged Americans,1 with an estimated prevalence of 2% to 5%.2 Untreated amblyopia results in poor vision for the lifetime of the child, increases the risk of injury to the sound eye, and may significantly reduce quality of life.3– 6 The treatment of amblyopia, including spectacle correction, full- or part-time occlusion of the sound eye, and atropine penalization of the sound eye is highly successful7–11 and cost effective.6 However, treatment must be delivered within the critical period of visual development. Amblyopia is unlikely to improve spontaneously.12 A major challenge in amblyopia prevention is the identification of at-risk children. Vision screening programs serve to detect amblyopia or its risk factors and refer identified children for treatment. However, of approximately 4 million preschool children in the United States, only approximately 20% are screened for amblyopia, and most are screened relatively late in the critical period.1,13 The past 2 decades have seen the development of nontraditional vision screening methods to increase the capture of at-risk children, including programs utilizing automated autorefractors, photorefractors, and photoscreeners. Offaxis photoscreeners, such as the Medical Technology, Incorporated (MTI) Photoscreener, are portable, inexpensive tools that can be implemented in a widespread vision screening program. Such screening programs are useful in © 2010 by the American Academy of Ophthalmology Published by Elsevier Inc.
identifying children with amblyopiogenic risk factors, including strabismus, anisometropia, astigmatism, and high refractive error.14 –17 The Lions Clubs of Tennessee have an established network of volunteer personnel that have been screening preschool children (ages 6 –72 months) in the community since September 1997. Trained staff interprets the images obtained from the Medical Technology, Incorporated Photoscreener, and a referral system of optometrists and ophthalmologists is in place to examine at-risk children. To date, ⬎200 000 children have been screened in Tennessee. The details of this program have been extensively described in the literature.14,18,19 It has been argued that identification of at-risk children before grade school may not be necessary or cost effective.20 The United States Preventative Services Task Force “recommends screening to detect amblyopia, strabismus, and defects in visual acuity in children younger than age 5 years”; however, it concedes that there is no direct evidence that preschool screening results in visual acuity improvement.21 It is the goal of this study to determine if at-risk children referred from a photoscreening program and subsequently diagnosed with amblyopia can be treated successfully.
Methods This study was a retrospective case-series chart review analyzing the efficacy of amblyopia treatment of children identified by phoISSN 0161-6420/10/$–see front matter doi:10.1016/j.ophtha.2009.06.041
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Ophthalmology Volume 117, Number 1, January 2010 Table 1. Amblyopiogenic Risk Factors Used for Referral from Photoscreening Risk Factor
Parameter
Anisometropia Hypermetropia Myopia Astigmatism Astigmatism Manifest strabismus Media opacity Ptosis with MRD
⬎1.00 D ⬎3.50 D ⬎⫺3.00 D ⬎1.5 D at 90° or 180° ⬎1.0 D in oblique axis ⬎1 mm ⬍1 mm
D ⫽ diopters; MRD ⫽ marginal-reflex distance.
toscreening and treated at a single academic pediatric ophthalmology practice. The study was approved by the Vanderbilt University Medical Center institutional review board and was compliant with Health Insurance Portability and Accountability Act requirements. Photoscreening was conducted by a volunteer staff from Tennessee Lion’s Clubs using the Medical Technology, Incorporated Photoscreener, with interpretation of the photographs done by trained personnel at the Vanderbilt Ophthalmic Imaging Center using our standard, published grading criteria.18 Referred children were evaluated by local optometrists and ophthalmologists. The risk factors used for the diagnosis of an amblyopiogenic factor on gold standard follow-up examination have been reported previously22 (Table 1). From September 1997 to December 2006, a total of 901 children screened by this program were directly referred to and examined by 1 of the 4 Vanderbilt Eye Institute pediatric ophthalmologists. Formal examinations were conducted on these children to confirm the presence of amblyopia or an amblyopiogenic risk factor. Examination included age-appropriate visual acuity testing, sensorimotor examination with quantification of strabismus, cycloplegic refraction, and dilated fundus examination. Age-appropriate best-corrected visual acuity testing involved fixation preference determination and HOTV single-surround optotypes, when possible. Results from this gold standard examination were stored in a database, which we queried to identify those children who were treated at Vanderbilt. From a review of the patient clinic chart, we recorded age, gender, near and distance best-corrected visual acuity, cycloplegic refraction, and associated ophthalmic diagnoses, as well as presence, type, and depth of amblyopia. Distance visual acuity was used for analysis except when only near acuity was recorded. Amblyopia was defined as a 2-line or more difference in visual acuity between the 2 eyes without an underlying ophthalmic or neurologic cause. Mild amblyopia was defined as a 2- to 3-line difference, moderate amblyopia was a 4- to 5-line difference, and severe amblyopia was a 6-line or greater difference, as described previously.23 Preliterate children were tested for fixation preference, using the induced tropia test in nonstrabismic children. Mild amblyopia was defined as central, steady, unmaintained versus central, steady, maintained (CSUM vs CSM), moderate amblyopia as uncentral, steady, unmaintained versus central, steady, maintained (UCSUM vs CSM), and severe amblyopia as uncentral, unsteady, unmaintained versus central, steady, maintained (UCUSUM vs CSM).23 Children with fixation preference testing were only included in analyses of relative visual acuity change with treatment, and not in analyses of absolute visual acuity because there is no standard conversion to Snellen acuity. Amblyopia type was recorded as anisometropic, strabismic, or mixed. Anisometropia was defined as at least a 1.00-diopter dif-
160
ference in spherical or cylindrical refractive error. Strabismic amblyopia was defined as amblyopia in the presence of any tropia. Children diagnosed with amblyopia were treated with standard therapy, including spectacles, full- or part-time patching, and/or atropine penalization at the discretion of the treating ophthalmologist. Treatment completion was defined as the visit when the physician recommended discontinuation of patching and/or atropine penalization. Amblyopic children were excluded from analysis if there was associated developmental delay and/or organic eye disease. Subjects were also excluded if there were ⬍2 clinic visits or insufficient documentation of visual acuity. Successful treatment of amblyopia in literate children was defined using the criteria of ⱖ3 lines improvement and/or 20/30 or better vision in the amblyopic eye.7 In children who were initially preliterate, successful treatment was defined as 20/30 or better vision in the amblyopic eye. Statistical analyses were conducted using paired t tests and chi-square contingency tables, as appropriate.
Results From September 1, 1997, to December 31, 2006, 901 children referred from photoscreening were evaluated by the pediatric ophthalmology service at the Vanderbilt Eye Institute. During this period, approximately 200 000 total children were screened and approximately 8000 were referred to various local optometrists and ophthalmologists. We studied only the children referred to the Vanderbilt Eye Institute. Of the 901 referred children examined at Vanderbilt Eye Institute, 736 either had an amblyopiogenic risk factor or were diagnosed with amblyopia (positive predictive value of these referrals ⫽ 82%). Using the criteria outlined in the Methods, 185 (21%) children were diagnosed with amblyopia. Sixty (32%) of these children did not meet the inclusion criteria. Therefore, a total of 125 children were included in the analyses (Table 2). The mean value ⫾ standard deviation (SD) age at presentation was 3.6⫾1.4 years, and 52% were female. The most common cause of amblyopia was anisometropia (63%), followed by mixed strabismus/anisometropia (32%) and strabismus (5%). Mild amblyopia was most common (48%), with both moderate amblyopia (19%) and severe amblyopia (33%) represented. There was no association between the type of amblyopia and depth of amblyopia (chi-square ⫽ 3.93; P ⫽ 0.690). The mean ⫾ SD follow-up period was 2.9⫾1.9 years, involving 7.9⫾4.5 clinic visits. Overall, 97 of the 125 (78%) children met criteria for successful treatment. Eighty-four of the 101 (83%) literate children were Table 2. Distribution of Referrals from Photoscreening Program n Total referrals from photoscreening False positives At risk Amblyopia Excluded Included Literate at entry Developed literacy
901 165 551 185 60 125 101 24
Of 901 children referred from our community photoscreening program, 736 either had an amblyopiogenic risk factor or were diagnosed with amblyopia (positive predictive value of 82%). Of the 185 children diagnosed with amblyopia, 125 were included in the analysis.
Teed et al 䡠 Amblyopia Therapy and Photoscreening
Figure 1. Graph depicting mean and standard error bars of logMAR visual acuity before and after amblyopia therapy in the affected and sound eye. logMAR, logarithm of minimal angle of resolution.
successfully treated. Of the 24 children who were initially preliterate, 13 (54%) demonstrated 20/30 or better visual acuity at the final examination. The mean ⫾ SD logarithm of minimal angle of resolution (logMAR) visual acuity at presentation in the amblyopic eye of children with quantifiable acuity was 0.63⫾0.30 and in the sound eye was 0.14⫾0.13 (t ⫽ 14.8; P⬍0.001). This approximates to a mean Snellen line difference of 4.4, with an average acuity of 20/84 and 20/28, respectively. Amblyopia therapy was efficacious in improving the vision of the amblyopic eye. After treatment, the mean ⫾ SD logMAR visual acuity in the amblyopic eye of all treated children was 0.25⫾0.24 and in the sound eye was 0.08⫾0.09 (t ⫽ 7.73; P⬍0.001). This approximates to a Snellen visual acuity of 20/36 in the amblyopic eye and 20/24 in the sound eye (Fig 1). There was significant improvement in the amblyopic eye with treatment (t ⫽ 10.6; P⬍0.001), with a mean improvement of 3.3 Snellen lines. The posttreatment visual acuity in the amblyopic eye of the initially literate children was logMAR 0.24⫾0.23 (Snellen approximate 20/35), and the posttreatment visual acuity in the amblyopic eye of the initially preliterate children was logMAR 0.29⫾0.24 (Snellen approximate 20/39). This was not significantly different (t ⫽ 1.09; P ⫽ 0.29). All depths of amblyopia responded to therapy; there was no association between depth of amblyopia and treatment success (chi-square ⫽ 3.21; P ⫽ 0.202). Similarly, there was no significant impact of amblyopia type on likelihood of treatment success (chi-square ⫽ 4.17; P ⫽ 0.250). There was no association between the sex of the child and treatment success (chi-square ⫽ 2.77; P ⫽ 0.100) or between the individual treating pediatric ophthalmologist and likelihood of treatment success (chi-square ⫽ 3.97; P ⫽ 0.273). However, there was a significant effect on the age of the child and likelihood of treatment success: the successfully treated children were more likely to be older at presentation (3.70 vs 3.07 years; t ⫽ 2.16; P ⫽ 0.033).
Discussion It is widely recognized that preschool photoscreening programs can appropriately identify children having amblyopiogenic risk factors,14 –18 and that vision screening can reduce amblyopia prevalence.24 Because these screening programs identify at-risk individuals during the time period when treatment is highly successful, one would expect that amblyopic children identified by photoscreening should respond well to therapy. Our study indeed confirms that such children can be successfully treated.
The 78% rate of successful treatment in our study is comparable with previous studies of amblyopia treatment. A potentially more relevant measure of amblyopia therapy is the percentage of children achieving very good visual acuity. In our study, 74% of children attained 20/40 vision in the amblyopic eye, 58% attained 20/30 vision, and 11% attained 20/20 vision. Our observed 3.3 Snellen lines of acuity improvement is similar to the magnitude of improvement seen in the 2-year follow-up data from the Amblyopia Treatment Study 1 (ATS1; 3.7 Snellen lines in the patching group and 3.6 Snellen lines in the atropine group).25 It must be recognized, however, that ATS1 was a study of moderate amblyopia (defined as 20/40 to 20/100 vision with ⱖ3 lines of intereye difference), whereas our study included all depths of amblyopia, and one third of our children had severe amblyopia of ⬎6 lines difference. Our satisfactory success rate for amblyopia therapy extended across all types and all depths of amblyopia. A more direct comparison with the 2-year follow-up data of the ATS1 trial is possible by looking at a select subgroup of our patients. We found 50 literate patients in our study with visual acuity in the amblyopic eye of 20/40 to 20/100 and at least a 3-line intereye difference, as required for inclusion in the ATS1 trial. Forty (80%) of these children were successfully treated. Eighty-six percent of these children attained 20/40 or better vision in the amblyopic eye, 64% attained 20/30 or better vision, and 14% attained 20/20 or better vision. This is comparable with the ATS1 2-year data, in which 88% had 20/40 or better vision, 73% had 20/32 or better vision, and 26% had 20/20 or better vision.25 Assessing the magnitude of amblyopia treatment response is difficult in preliterate children, because fixation preference is a qualitative measure and the validity of such testing may be suspect.26 Nonetheless, it is important to include such children in studies of amblyopia therapy, because early invention can be effective.27 As mentioned, their inclusion did not influence the analysis of the magnitude of acuity improvement, but could result in an underestimation of overall treatment success, as the only criterion for successful treatment was 20/30 or better visual acuity. In comparing our success rate with other studies of amblyopia, it must be stressed that our study group consists of referrals from a photoscreening program. It is our assumption that children with manifest strabismus will have previously been referred for evaluation. This results in an overrepresentation of anisometropia in our study group as compared with studies of amblyopia therapy (63% compared with 37% in the ATS1).7 Nonetheless, all types of amblyopia were successfully and equally treated. The limitations of our retrospective review include nonstandardized visual acuity measurements, variability in amblyopia treatment, and uncertainty in the diagnosis and treatment of amblyopia in preliterate children. These limitations, however, approximate real-world clinical management of amblyopia. The data presented herein suggest that photoscreening programs can identify at-risk children who can subsequently be successfully treated. These programs can be a useful adjunct in the prevention of amblyopia-related vision loss.
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References 15. 1. National Eye Institute. Visual Acuity Impairment Survey Pilot Study. Springfield, VA: National Technical Information Service; 1984:81– 4. NTIS no. PB84-156173. 2. Simons K. Preschool vision screening: rationale, methodology, and outcome. Surv Ophthalmol 1996;41:3–30. 3. Rahi J, Logan S, Timms C, et al. Risks, causes, and outcomes of visual impairment after loss of vision in the non-amblyopic eye: a population-based study. Lancet 2002;360:597– 602. 4. Tommila V, Tarkkanen A. Incidence of loss of vision in the healthy eye in amblyopia. Br J Ophthalmol 1981;65:575–7. 5. Chua B, Mitchell P. Consequences of amblyopia on education, occupation, and long term vision loss. Br J Ophthalmol 2004; 88:1119 –21. 6. Membreno JH, Brown MM, Brown GC, et al. A cost-utility analysis of therapy for amblyopia. Ophthalmology 2002;109: 2265–71. 7. Pediatric Eye Disease Investigator Group. A randomized trial of atropine vs patching for treatment of moderate amblyopia in children. Arch Ophthalmol 2002;120:268 –78. 8. Pediatric Eye Disease Investigator Group. A comparison of atropine and patching treatments for moderate amblyopia by patient age, cause of amblyopia, depth of amblyopia, and other factors. Ophthalmology 2003;110:1632–7. 9. Pediatric Eye Disease Investigator Group. A randomized trial of patching regimens for treatment of moderate amblyopia in children. Arch Ophthalmol 2003;121:603–11. 10. Pediatric Eye Disease Investigator Group. A randomized trial of prescribed patching regimens for treatment of severe amblyopia in children. Ophthalmology 2003;110:2075– 87. 11. Pediatric Eye Disease Investigator Group. A randomized trial of atropine regimens for treatment of moderate amblyopia in children. Ophthalmology 2004;111:2076 – 85. 12. Simons K, Preslan M. Natural history of amblyopia untreated owing to lack of compliance. Br J Ophthalmol 1999;83:582–7. 13. Schmidt PP. Screening for the vision problems of young children. In: Moore BD, ed. Eye Care for Infants and Young Children. Boston: Butterworth-Heinemann; 1997:175– 89. 14. Donahue SP, Johnson TM, Leonard-Martin TC. Screening for amblyogenic factors using a volunteer lay network and the MTI PhotoScreener: initial results from 15,000 preschool chil-
16. 17. 18. 19.
20. 21. 22. 23. 24. 25.
26.
27.
dren in a statewide effort. Ophthalmology 2000;107:1637– 44; discussion 1645– 6. Tong PY, Enke-Miyazaki E, Bassin RE, et al, National Children’s Eye Care Foundation Vision Screening Study Group. Screening for amblyopia in preverbal children with photoscreening photographs. Ophthalmology 1998;105:856 – 63. Ottar WL, Scott WE, Holgado SI. Photoscreening for amblyogenic factors. J Pediatr Ophthalmol Strabismus 1995;32:289 –95. Donahue SP, Johnson TM, Ottar WL, Scott WE. Sensitivity of photoscreening to detect high-magnitude amblyogenic factors. J AAPOS 2002;6:86 –91. Donahue SP, Johnson TM. Age-based refinement of referral criteria for photoscreening. Ophthalmology 2001;108:2309 – 14; discussion 2314 –5. Donahue SP, Baker JD, Scott WE, et al. Lions Club International Foundation Core Four Photoscreening: results from 17 programs and 400,000 preschool children. J AAPOS 2006;10: 44 – 8. Moseley MJ, Fielder AR. Preschool vision screening. Br J Ophthalmol 2003;87:931. U.S. Preventive Services Task Force. Screening for visual impairment in children younger than age 5 years: recommendation statement. Ann Fam Med 2004;2:263– 6. Salcido AA, Bradley J, Donahue SP. Predictive value of photoscreening and traditional screening of preschool children. J AAPOS 2005;9:114 –20. Donahue SP. Relationship between anisometropia, patient age, and the development of amblyopia. Am J Ophthalmol 2006;142:132– 40. Eibschitz-Tsimhoni M, Friedman T, Naor J, et al. Early screening for amblyogenic risk factors lowers the prevalence and severity of amblyopia. J AAPOS 2000;4:194 –9. Pediatric Eye Disease Investigator Group. Two-year follow-up of a 6-month randomized trial of atropine vs patching for treatment of moderate amblyopia in children. Arch Ophthalmol 2005;123:149 –57. Friedman DS, Katz J, Repka MX, et al. Lack of concordance between fixation preference and HOTV optotype visual acuity in preschool children: the Baltimore Pediatric Eye Disease Study. Ophthalmology 2008;115:1796 –9. Kirk VG, Clausen MM, Armitage M, Arnold RW. Preverbal photoscreening for amblyogenic factors and outcomes in amblyopia treatment: early objective screening and visual acuities. Arch Ophthalmol 2008;126:489 –92.
Footnotes and Financial Disclosures Originally received: January 13, 2009. Final revision: June 19, 2009. Accepted: June 19, 2009. Available online: November 5, 2009.
Presented as paper 075 at: the American Academy of Ophthalmology Annual Meeting, November 11, 2008, Atlanta, Georgia. Manuscript no. 2009-55.
1
Department of Ophthalmology, Vanderbilt University School of Medicine, Nashville, Tennessee. 2
Department of Neurology, Vanderbilt University School of Medicine, Nashville, Tennessee. 3
Department Pediatrics, Vanderbilt University School of Medicine, Nashville, Tennessee.
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Financial Disclosure(s): The authors have no proprietary or commercial interest in any of the materials discussed in this article. Correspondence: Ronald G. Teed, MD, Storm Eye Institute, Medical University of South Carolina, 167 Ashley Avenue, Charleston, SC 29425. E-mail: teed@ musc.edu.
Amblyopia is the leading cause of monocular vision impairment in young and middle-aged Americans,1 with an estimated prevalence of 2% to 5%.2 Untreated amblyopia results in poor vision for the lifetime of the child, increases the risk of injury to the sound eye, and may significantly reduce quality of life.3– 6 The treatment of amblyopia, including spectacle correction, full- or part-time occlusion of the sound eye, and atropine penalization of the sound eye is highly successful7–11 and cost effective.6 However, treatment must be delivered within the critical period of visual development. Amblyopia is unlikely to improve spontaneously.12 A major challenge in amblyopia prevention is the identification of at-risk children. Vision screening programs serve to detect amblyopia or its risk factors and refer identified children for treatment. However, of approximately 4 million preschool children in the United States, only approximately 20% are screened for amblyopia, and most are screened relatively late in the critical period.1,13 The past 2 decades have seen the development of nontraditional vision screening methods to increase the capture of at-risk children, including programs utilizing automated autorefractors, photorefractors, and photoscreeners. Offaxis photoscreeners, such as the Medical Technology, Incorporated (MTI) Photoscreener, are portable, inexpensive tools that can be implemented in a widespread vision screening program. Such screening programs are useful in © 2010 by the American Academy of Ophthalmology Published by Elsevier Inc.
identifying children with amblyopiogenic risk factors, including strabismus, anisometropia, astigmatism, and high refractive error.14 –17 The Lions Clubs of Tennessee have an established network of volunteer personnel that have been screening preschool children (ages 6 –72 months) in the community since September 1997. Trained staff interprets the images obtained from the Medical Technology, Incorporated Photoscreener, and a referral system of optometrists and ophthalmologists is in place to examine at-risk children. To date, ⬎200 000 children have been screened in Tennessee. The details of this program have been extensively described in the literature.14,18,19 It has been argued that identification of at-risk children before grade school may not be necessary or cost effective.20 The United States Preventative Services Task Force “recommends screening to detect amblyopia, strabismus, and defects in visual acuity in children younger than age 5 years”; however, it concedes that there is no direct evidence that preschool screening results in visual acuity improvement.21 It is the goal of this study to determine if at-risk children referred from a photoscreening program and subsequently diagnosed with amblyopia can be treated successfully.
Methods This study was a retrospective case-series chart review analyzing the efficacy of amblyopia treatment of children identified by phoISSN 0161-6420/10/$–see front matter doi:10.1016/j.ophtha.2009.06.041
159
Ophthalmology Volume 117, Number 1, January 2010 Table 1. Amblyopiogenic Risk Factors Used for Referral from Photoscreening Risk Factor
Parameter
Anisometropia Hypermetropia Myopia Astigmatism Astigmatism Manifest strabismus Media opacity Ptosis with MRD
⬎1.00 D ⬎3.50 D ⬎⫺3.00 D ⬎1.5 D at 90° or 180° ⬎1.0 D in oblique axis ⬎1 mm ⬍1 mm
D ⫽ diopters; MRD ⫽ marginal-reflex distance.
toscreening and treated at a single academic pediatric ophthalmology practice. The study was approved by the Vanderbilt University Medical Center institutional review board and was compliant with Health Insurance Portability and Accountability Act requirements. Photoscreening was conducted by a volunteer staff from Tennessee Lion’s Clubs using the Medical Technology, Incorporated Photoscreener, with interpretation of the photographs done by trained personnel at the Vanderbilt Ophthalmic Imaging Center using our standard, published grading criteria.18 Referred children were evaluated by local optometrists and ophthalmologists. The risk factors used for the diagnosis of an amblyopiogenic factor on gold standard follow-up examination have been reported previously22 (Table 1). From September 1997 to December 2006, a total of 901 children screened by this program were directly referred to and examined by 1 of the 4 Vanderbilt Eye Institute pediatric ophthalmologists. Formal examinations were conducted on these children to confirm the presence of amblyopia or an amblyopiogenic risk factor. Examination included age-appropriate visual acuity testing, sensorimotor examination with quantification of strabismus, cycloplegic refraction, and dilated fundus examination. Age-appropriate best-corrected visual acuity testing involved fixation preference determination and HOTV single-surround optotypes, when possible. Results from this gold standard examination were stored in a database, which we queried to identify those children who were treated at Vanderbilt. From a review of the patient clinic chart, we recorded age, gender, near and distance best-corrected visual acuity, cycloplegic refraction, and associated ophthalmic diagnoses, as well as presence, type, and depth of amblyopia. Distance visual acuity was used for analysis except when only near acuity was recorded. Amblyopia was defined as a 2-line or more difference in visual acuity between the 2 eyes without an underlying ophthalmic or neurologic cause. Mild amblyopia was defined as a 2- to 3-line difference, moderate amblyopia was a 4- to 5-line difference, and severe amblyopia was a 6-line or greater difference, as described previously.23 Preliterate children were tested for fixation preference, using the induced tropia test in nonstrabismic children. Mild amblyopia was defined as central, steady, unmaintained versus central, steady, maintained (CSUM vs CSM), moderate amblyopia as uncentral, steady, unmaintained versus central, steady, maintained (UCSUM vs CSM), and severe amblyopia as uncentral, unsteady, unmaintained versus central, steady, maintained (UCUSUM vs CSM).23 Children with fixation preference testing were only included in analyses of relative visual acuity change with treatment, and not in analyses of absolute visual acuity because there is no standard conversion to Snellen acuity. Amblyopia type was recorded as anisometropic, strabismic, or mixed. Anisometropia was defined as at least a 1.00-diopter dif-
160
ference in spherical or cylindrical refractive error. Strabismic amblyopia was defined as amblyopia in the presence of any tropia. Children diagnosed with amblyopia were treated with standard therapy, including spectacles, full- or part-time patching, and/or atropine penalization at the discretion of the treating ophthalmologist. Treatment completion was defined as the visit when the physician recommended discontinuation of patching and/or atropine penalization. Amblyopic children were excluded from analysis if there was associated developmental delay and/or organic eye disease. Subjects were also excluded if there were ⬍2 clinic visits or insufficient documentation of visual acuity. Successful treatment of amblyopia in literate children was defined using the criteria of ⱖ3 lines improvement and/or 20/30 or better vision in the amblyopic eye.7 In children who were initially preliterate, successful treatment was defined as 20/30 or better vision in the amblyopic eye. Statistical analyses were conducted using paired t tests and chi-square contingency tables, as appropriate.
Results From September 1, 1997, to December 31, 2006, 901 children referred from photoscreening were evaluated by the pediatric ophthalmology service at the Vanderbilt Eye Institute. During this period, approximately 200 000 total children were screened and approximately 8000 were referred to various local optometrists and ophthalmologists. We studied only the children referred to the Vanderbilt Eye Institute. Of the 901 referred children examined at Vanderbilt Eye Institute, 736 either had an amblyopiogenic risk factor or were diagnosed with amblyopia (positive predictive value of these referrals ⫽ 82%). Using the criteria outlined in the Methods, 185 (21%) children were diagnosed with amblyopia. Sixty (32%) of these children did not meet the inclusion criteria. Therefore, a total of 125 children were included in the analyses (Table 2). The mean value ⫾ standard deviation (SD) age at presentation was 3.6⫾1.4 years, and 52% were female. The most common cause of amblyopia was anisometropia (63%), followed by mixed strabismus/anisometropia (32%) and strabismus (5%). Mild amblyopia was most common (48%), with both moderate amblyopia (19%) and severe amblyopia (33%) represented. There was no association between the type of amblyopia and depth of amblyopia (chi-square ⫽ 3.93; P ⫽ 0.690). The mean ⫾ SD follow-up period was 2.9⫾1.9 years, involving 7.9⫾4.5 clinic visits. Overall, 97 of the 125 (78%) children met criteria for successful treatment. Eighty-four of the 101 (83%) literate children were Table 2. Distribution of Referrals from Photoscreening Program n Total referrals from photoscreening False positives At risk Amblyopia Excluded Included Literate at entry Developed literacy
901 165 551 185 60 125 101 24
Of 901 children referred from our community photoscreening program, 736 either had an amblyopiogenic risk factor or were diagnosed with amblyopia (positive predictive value of 82%). Of the 185 children diagnosed with amblyopia, 125 were included in the analysis.
Teed et al 䡠 Amblyopia Therapy and Photoscreening
Figure 1. Graph depicting mean and standard error bars of logMAR visual acuity before and after amblyopia therapy in the affected and sound eye. logMAR, logarithm of minimal angle of resolution.
successfully treated. Of the 24 children who were initially preliterate, 13 (54%) demonstrated 20/30 or better visual acuity at the final examination. The mean ⫾ SD logarithm of minimal angle of resolution (logMAR) visual acuity at presentation in the amblyopic eye of children with quantifiable acuity was 0.63⫾0.30 and in the sound eye was 0.14⫾0.13 (t ⫽ 14.8; P⬍0.001). This approximates to a mean Snellen line difference of 4.4, with an average acuity of 20/84 and 20/28, respectively. Amblyopia therapy was efficacious in improving the vision of the amblyopic eye. After treatment, the mean ⫾ SD logMAR visual acuity in the amblyopic eye of all treated children was 0.25⫾0.24 and in the sound eye was 0.08⫾0.09 (t ⫽ 7.73; P⬍0.001). This approximates to a Snellen visual acuity of 20/36 in the amblyopic eye and 20/24 in the sound eye (Fig 1). There was significant improvement in the amblyopic eye with treatment (t ⫽ 10.6; P⬍0.001), with a mean improvement of 3.3 Snellen lines. The posttreatment visual acuity in the amblyopic eye of the initially literate children was logMAR 0.24⫾0.23 (Snellen approximate 20/35), and the posttreatment visual acuity in the amblyopic eye of the initially preliterate children was logMAR 0.29⫾0.24 (Snellen approximate 20/39). This was not significantly different (t ⫽ 1.09; P ⫽ 0.29). All depths of amblyopia responded to therapy; there was no association between depth of amblyopia and treatment success (chi-square ⫽ 3.21; P ⫽ 0.202). Similarly, there was no significant impact of amblyopia type on likelihood of treatment success (chi-square ⫽ 4.17; P ⫽ 0.250). There was no association between the sex of the child and treatment success (chi-square ⫽ 2.77; P ⫽ 0.100) or between the individual treating pediatric ophthalmologist and likelihood of treatment success (chi-square ⫽ 3.97; P ⫽ 0.273). However, there was a significant effect on the age of the child and likelihood of treatment success: the successfully treated children were more likely to be older at presentation (3.70 vs 3.07 years; t ⫽ 2.16; P ⫽ 0.033).
Discussion It is widely recognized that preschool photoscreening programs can appropriately identify children having amblyopiogenic risk factors,14 –18 and that vision screening can reduce amblyopia prevalence.24 Because these screening programs identify at-risk individuals during the time period when treatment is highly successful, one would expect that amblyopic children identified by photoscreening should respond well to therapy. Our study indeed confirms that such children can be successfully treated.
The 78% rate of successful treatment in our study is comparable with previous studies of amblyopia treatment. A potentially more relevant measure of amblyopia therapy is the percentage of children achieving very good visual acuity. In our study, 74% of children attained 20/40 vision in the amblyopic eye, 58% attained 20/30 vision, and 11% attained 20/20 vision. Our observed 3.3 Snellen lines of acuity improvement is similar to the magnitude of improvement seen in the 2-year follow-up data from the Amblyopia Treatment Study 1 (ATS1; 3.7 Snellen lines in the patching group and 3.6 Snellen lines in the atropine group).25 It must be recognized, however, that ATS1 was a study of moderate amblyopia (defined as 20/40 to 20/100 vision with ⱖ3 lines of intereye difference), whereas our study included all depths of amblyopia, and one third of our children had severe amblyopia of ⬎6 lines difference. Our satisfactory success rate for amblyopia therapy extended across all types and all depths of amblyopia. A more direct comparison with the 2-year follow-up data of the ATS1 trial is possible by looking at a select subgroup of our patients. We found 50 literate patients in our study with visual acuity in the amblyopic eye of 20/40 to 20/100 and at least a 3-line intereye difference, as required for inclusion in the ATS1 trial. Forty (80%) of these children were successfully treated. Eighty-six percent of these children attained 20/40 or better vision in the amblyopic eye, 64% attained 20/30 or better vision, and 14% attained 20/20 or better vision. This is comparable with the ATS1 2-year data, in which 88% had 20/40 or better vision, 73% had 20/32 or better vision, and 26% had 20/20 or better vision.25 Assessing the magnitude of amblyopia treatment response is difficult in preliterate children, because fixation preference is a qualitative measure and the validity of such testing may be suspect.26 Nonetheless, it is important to include such children in studies of amblyopia therapy, because early invention can be effective.27 As mentioned, their inclusion did not influence the analysis of the magnitude of acuity improvement, but could result in an underestimation of overall treatment success, as the only criterion for successful treatment was 20/30 or better visual acuity. In comparing our success rate with other studies of amblyopia, it must be stressed that our study group consists of referrals from a photoscreening program. It is our assumption that children with manifest strabismus will have previously been referred for evaluation. This results in an overrepresentation of anisometropia in our study group as compared with studies of amblyopia therapy (63% compared with 37% in the ATS1).7 Nonetheless, all types of amblyopia were successfully and equally treated. The limitations of our retrospective review include nonstandardized visual acuity measurements, variability in amblyopia treatment, and uncertainty in the diagnosis and treatment of amblyopia in preliterate children. These limitations, however, approximate real-world clinical management of amblyopia. The data presented herein suggest that photoscreening programs can identify at-risk children who can subsequently be successfully treated. These programs can be a useful adjunct in the prevention of amblyopia-related vision loss.
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Footnotes and Financial Disclosures Originally received: January 13, 2009. Final revision: June 19, 2009. Accepted: June 19, 2009. Available online: November 5, 2009.
Presented as paper 075 at: the American Academy of Ophthalmology Annual Meeting, November 11, 2008, Atlanta, Georgia. Manuscript no. 2009-55.
1
Department of Ophthalmology, Vanderbilt University School of Medicine, Nashville, Tennessee. 2
Department of Neurology, Vanderbilt University School of Medicine, Nashville, Tennessee. 3
Department Pediatrics, Vanderbilt University School of Medicine, Nashville, Tennessee.
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Financial Disclosure(s): The authors have no proprietary or commercial interest in any of the materials discussed in this article. Correspondence: Ronald G. Teed, MD, Storm Eye Institute, Medical University of South Carolina, 167 Ashley Avenue, Charleston, SC 29425. E-mail: teed@ musc.edu.