Diagnostic accuracy of vision screening tests for the ... - Springer Link

Graefes Arch Clin Exp Ophthalmol (2009) 247:1441–1454 DOI 10.1007/s00417-009-1150-2

REVIEW ARTICLE

Diagnostic accuracy of vision screening tests for the detection of amblyopia and its risk factors: a systematic review Christine Schmucker & Robert Grosselfinger & Rob Riemsma & Gerd Antes & Stefan Lange & Wolf Lagrèze & Jos Kleijnen

Received: 28 January 2009 / Revised: 30 June 2009 / Accepted: 13 July 2009 / Published online: 11 August 2009 # Springer-Verlag 2009

Abstract Aim This systematic review evaluates the diagnostic accuracy of preschool vision screening tests for the detection of amblyopia and its risk factors. Methods The literature searches were conducted in nine bibliographic databases. No limitation to a specific study

design, year of publication or language was applied. Studies were included if they compared a vision screening test with a reference test (gold standard) in children from the general population. In addition, the studies had to provide sufficient data to calculate diagnostic accuracy (sensitivity and specificity). Full-text articles were assessed for studies that

The project was referred by the Federal Joint Committee (Gemeinsamer Bundesausschuss, Auf dem Seidenberg 3a, 53721 Siegburg, Germany) to the Institute for Quality and Efficiency in Health Care (Institut für Qualität und Wirtschaftlichkeit im Gesundheitswesen [IQWiG], Dillenburger Str. 27, 51105 Cologne, Germany). IQWiG commissioned the review to be prepared by Kleijnen Systematic Reviews Ltd and the German Cochrane Center. IQWiG prepared the final version of the full study report on which this paper is based, and funded the researchers and authors. JK, RG and SL developed the protocol and design of the study. Study selection and data extraction was carried out by CS, JK, SL, RG and RR. WL provided clinical advice, and GA provided methodological support. All authors were involved in data interpretation and had full access to all of the data, and they agree to allow Graefe’s Archive for Clinical and Experimental Ophthalmology to review their data upon request. CS wrote the paper. All authors commented on drafts of the paper and approved the final version. C. Schmucker (*) : G. Antes German Cochrane Centre, Institute of Medical Biometry and Medical Informatics, Department of Medical Biometry and Statistics, University Medical Centre Freiburg, Stefan-Meier-Str. 26, 79104 Freiburg, Germany e-mail: [email protected]

R. Grosselfinger : S. Lange Department of Non-drug Interventions, Institute for Quality and Efficiency in Health Care, Dillenburger Str. 27, 51105 Cologne, Germany

W. Lagrèze University Eye Hospital Freiburg, Killianstr. 5, 79106 Freiburg, Germany

J. Kleijnen The School for Public Health and Primary Care (Caphri), Maastricht University, Maastricht, Netherlands

R. Riemsma : J. Kleijnen Kleijnen Systematic Reviews Ltd, Westminster Business Centre, 10 Great North Way, Nether Poppleton, York YO26 6RB, United Kingdom

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satisfied the inclusion criteria using the “Quality of Diagnostic Accuracy Studies (QUADAS)” checklist. Results Two studies with a longitudinal design and 25 crosssectional studies met the inclusion criteria. One of the longitudinal studies compared a screening programme in children between 1 and 2 years of age with a re-examination at the age of 8. The sensitivity for the screening programme was 86% (range: 64–97%) and the specificity 99% (range: 98–99%). The second longitudinal study compared screening examinations at 8, 12, 18, 25 and 31 months, with a re-examination at the age of 37 months. In this study, the sensitivity of the screening examination increased with age, while the specificity remained unchanged. The crosssectional studies evaluated different screening settings, visual acuity tests, auto- or photorefractors and stereo tests. A large variety of reference tests, differing criteria for defining amblyopia and its risk factors and methodological limitations of the studies prevented a valid data interpretation. Conclusion Diagnostic test accuracy of preschool vision screening tests can only be sufficiently investigated after establishing age-related values defining amblyopia, refractive errors and binocular disorders. To address these questions, we recommend a controlled longitudinal study design.

(e.g., Lea test, Snellen’s E test, Sheridan–Gardiner test or preferential looking test for infants), testing for ocular alignment (e.g., cover test, Hirschberg test), stereo acuity testing (e.g., Lang test, Random Dot E test) and noncycloplegic retinoscopy [9, 10]. Autorefractors and photorefractors are recently developed objective screening tools to detect amblyogenic factors such as refractive errors (autorefraction and photorefraction) or strabismus (photorefraction) [11, 12]. Although these devices are not included in screening recommendations [9], some studies suggest that automated vision screening may be a useful strategy to detect visual impairments in preschool-aged children [e.g., 13]. Despite the large number of screening tests available, little is known about the effectiveness and diagnostic accuracy of these tests. To be effective, a screening test must identify both a high proportion of children who have the target condition (= high sensitivity) and a high proportion of children without any visual disorders (= high specificity). We conducted a systematic review according to criteria of the UK National Screening Committee [14] to determine the diagnostic accuracy of common preschool vision screening tests for the detection of amblyopia and its risk factors in unselected children up to the age of 6 years.

Keywords Systematic review . Amblyopia . Preschool vision screening . Diagnostic test accuracy

Material and methods Systematic literature search

Introduction Amblyopia and its risk factors such as strabismus and refractive errors are the most common visual disorders in children. Across different ethnic groups and a wide range of countries (both Western and developing countries), the prevalence rate of amblyopia ranges between 0.3% and 3.0% [1–4]. Preschool vision screening programmes for amblyopia were developed in response to animal studies which suggest that early detection and treatment of visual impairments is more effective than treatment later in life [5, 6]. Currently, there are a variety of recommendations for identifying children with amblyopia or its risk factors. For example, some guidelines suggest that all preschool-aged children should undergo a comprehensive examination by an ophthalmologist, which can be regarded as the gold standard for diagnosing amblyopia or its risk factors [7]. In contrast, other authorities believe that vision screening can be conducted by a wide range of health professionals (e.g., general practitioners or nurses) and may be a more cost-effective way to identify children with visual impairments [8]. Recommendations for preschool vision screening tests include monocular visual acuity testing using an age-appropriate vision test

We searched nine bibliographic databases (Medline [Ovid], Embase, CINAHL, PSYCHinfo, Cochrane Central [CDSR, DARE, NHS EED, HTA], PSYNDEXplus, Social SciSearch, GIN and Medion) from inception until December 2007. The search strategy was based on combinations of medical subject headings (MeSH) and keywords. No restriction to a specific language was applied. The search strategy used in Medline (Ovid) is presented in the Appendix. The literature searches were modified to meet the requirements of each database. The searches were supplemented by handsearching the bibliographies of included studies. Additionally, enquiries were sent to manufacturers of screening tests. Inclusion criteria Four inclusion criteria were applied to evaluate diagnostic accuracy of preschool vision screening tests (also called “index test”):

(1) Studies including children from the general population up to the age of 6 years were eligible for this review. Studies which included children with

Graefes Arch Clin Exp Ophthalmol (2009) 247:1441–1454

specific diseases (such as diabetes, dyslexia, deafness or congenital diseases) and organic eye defects (such as congenital glaucoma, cataract or retinoblastoma) were excluded. (2) Studies were included if they provided sufficient information to calculate test accuracy (sensitivity and specificity) of the screening test. (3) Every reference test (a widely accepted test, gold standard test) and (4) Each study design was eligible for this review. Study selection, data extraction and quality assessment Titles and abstracts resulting from the literature searches were scanned. Full-text articles were obtained for all potentially relevant studies. Data extraction and quality assessment were carried out in those studies that satisfied the above mentioned inclusion criteria. We used 2×2 tables to calculate test sensitivity and specificity. The methodological quality of the trials (e.g., masking of outcome measurements, adequate reporting, independence of the screening and reference test) was assessed using the “Quality of Diagnostic Accuracy Studies (QUADAS)” checklist [15]. All stages of study selection, data extraction and quality assessment were handled independently by two reviewers (CS, RR, KSW, TJ or JK). Any disagreement during the selection, extraction and assessment process were resolved by discussion and consensus. Statistical analysis A meta-analysis could not be performed, due to the heterogeneity of the included studies. The results of the systematic review are presented in a narrative way.

Results Results of the searches and selection process The literature searches identified 28,882 references. After removing 2,938 duplicate references, we obtained 25,944 citations. This number also includes potentially relevant treatment studies, studies examining the effectiveness of screening programmes, and studies evaluating organic eye diseases. For the purpose of this review, 213 potentially relevant full-text articles were evaluated. We excluded 186 publications (186 studies) for the following reasons: (1) the study did not provide enough data to calculate sensitivity and specificity of the screening test (n=77), (2) the result of the screening test was not compared with the result of a

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reference test (n=8), and (3) the study included selected children (e.g., children with disabilities or organic eye disorders) (n=101). Description of the included studies The inclusion criteria were met by 27 studies [16–38, 40–43]. Five studies evaluated more than one screening test. Therefore, we considered 32 comparisons from 27 trials. The majority of studies (26 studies) calculated test accuracy (sensitivity and specificity) using the number of children. One study referred to the number of eyes [16]. A longitudinal study design was applied in two studies [17, 18] and a cross-sectional design in 25 studies. Evaluation of an early screening examination versus a reexamination at a later age Two longitudinal studies compared an early screening examination with an examination at a later age [17, 18]. The characteristics of these studies are presented in Table 1. The study of Eibschitz et al. [17] compared a screening programme in children between 12 and 30 months with a re-examination at the age of 8 years. The screening programme showed a sensitivity of 86% and a specificity of 99%. The second longitudinal study compared single screening tests or test combinations between different age groups (screening at the age of 8, 12, 18, 25 and 31 months versus screening at 37 months) [18]. Overall, the screening tests showed an increase of sensitivity with age, while specificity remained unchanged. One exception was photorefraction. This screening technique showed a comparatively high sensitivity even in 1-year-old children (over 60%). In addition, Williams et al. [18] compared the impact both of frequent eye examinations before 3 years of age (screening at the age of 8, 12, 18, 25 and 31 months) and a current screening programme (screening at 8 and 18 months) with a reference examination at the age of 37 months. The sensitivity for the intensive screening programme was 68%, whereas the current screening programme showed a sensitivity of 32%. Specificity was equally high for both programmes (95% and 92% respectively). Evaluation of different health professionals or screening settings Six cross-sectional studies compared different health professionals and/or different screening settings [19–24] (see Table 2). One of these studies evaluated whether there is a difference in the outcome when the STYCAR visual acuity test is administered by a nurse or an orthoptist [19]. The

e

d

c

b

a

Screening (between 12 and 30 mos) Retinoscopy + Strabismus test Intensive orthoptic screening (age: 8, 12, 18, 25, 31 months) Subgroupsb: Cover test + VA test (12 months)c: Cover test + VA test (31 months)c: Visual acuity test (12 months)d: Visual acuity test (31 months)d: Cover test (12 months)e: Cover test (31 months)e: Photorefraction (12 months)c: Photorefraction (31 months)c: Current screening programme (age: 8 and 18 months) Cover test + VA test

Index test

95 (94–96)

100 (99–100) 99 (99–100) 97 (95–98) 96 (95–97) 100 (99–100) 100 (99–100) 84 (81–86) 96 (95–97) 92 (91–94)

16 (07–30) 44 (30–60) 0 (00–20) 18 (04–43) 25 (11–45) 64 (44–81) 61 (41–79) 64 (44–81) 32 (20–46)

99 (98–99)

Specificitya

68 (56–79)

86 (64–97)

Sensitivitya

Main outcome: strabismus

Main outcome: amblyopia

Main outcome: amblyopia and strabismus

Sensitivity and specificity for the age of 8, 18 and 25 months are also presented in the publication [Williams et al. (2001)]

In %, in brackets: 95% confidence interval

VA: Visual acuity

988

Eibschitz-Tsimhoni et al. (2000) [17] (Israel) Williams et al. (2001) [18] (Great Britain)

2029

No. of included children

Study

3.5

2.2

Prevalence (%) Re-examination (at the age of 96 months) Retinoscopy + VA test Less intensive orthoptic screening (at the age of 37 months) Same tests + test combinations as Index test

Reference test

Table 1 Characteristics of studies evaluating a screening examination in younger children versus a re-examination at a later age (longitudinal studies)

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11734/54–66

1245/preschool children

400/36–47

766/60–71

De Becker et al. (1992) [21] (Canada)

Kennedy et al. (1995)* [22] (Canada)

Rasmussen et al. (2000) [23] (Sweden)

Spowart et al. (1998) [19] (Scottland) Wick et al. (1975) [24] (USA)

Age ≥ 41 months

Age 1 mm, astigmatism > 2 mm difference between horizontal and vertical photos in the same eye

Astigmatism > 2.5D and hyperopia > 5D; myopia > 4D, anisometropia > 1.5D

**

n

91 (82–96)l 82 (76–87)m 63 (44–79)n

53 (42–65)h 72 (61–82)i 63 (57–69)j 100 (99–100)k

96 (94–98)g

75 (62–85)g (55–98)h (52–98)i (31–79)j (30–63)k

97 (95–99)d 93 (90–95)e 58 (53–63)f

82 (60–95)d 86 (65–97)e 80 (44–98)f

85 83 56 46

Specificityb

Sensitivityb

Hyperopia: ratio crescent width:pupil diameter > 0.3 mm; anisometropia: any difference in ratio crescent width:pupil diameter

Hyperopia > 2.25D (off-axis)

Hyperopia > 0.75D (on-axis)

Hyperopia > 2D, myopia > 1D, astigmatism > 1D, anisometropia > 1.25D

Hyperopia > 3D, myopia > 1D, astigmatism > 1.5D, anisometropia > 1D

No cut-offs described

m

l

k

j

i

h

g

f

e

d

Autorefraction Photorefraction Photorefraction

Photorefraction Photorefraction

Photorefraction

Photorefraction

Videorefraction Autorefraction Autorefraction

Index test

Because of the large number of tests applied, no cut-offs are presented.

In %, in brackets: 95% confidence interval

Age-distribution or mean age ± standard deviation in months

Cut-off (index test)

c

b

a

VA: Visual acuity

No./agea included children

Study

Table 4 Characteristics of auto- and photoscreeners (cross-sectional studies)

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292/48–72

Briscoe et al. (1998)** [32] (Israel) Hope et al. (1990) [40] (New Zealand)

129/24–71

Walraven (1975) [43] (Netherlands)

Titmus stereotest

STBS STRDS 200″

if not recognised if not recognised

if not recognised if not recognised

unclear

600″

unclear

638″

Cut-off

(15–46) (10–56) (8–41) (39–79)

14 (0–58)

100 (3–100)c 100 (3–100)c

46 (27–67) 58 (37–77)

29 29 21 60

89 (52–100)

50 (16-84)

Sensitivityb

90 (83–95)

95 (89–98) 79 (71–86) 7.0

0.9

12.7

2.0 (strabismus) 1.0 (amblyopia) 1.6 (anisometropia) 12.6

5.4

27.7

Prevalence (%)

Because of the large number of individual tests applied, no cut-offs are presented

The sensitivity of 100% for both tests refers to a population with only one affected child. Study was planned to evaluate specificity

In %, in brackets: 95% confidence interval

Age-distribution in months

**Study evaluated different diagnostic tests and is listed the second time

d

c

b

a

(98–99) (98–99) (98–99) (86–95)

97 (94–99) 94 (89–97)

99 99 99 91

76 (68–82)

99 (97–100)

Specificityb

VA: Visual acuity. ’’: Seconds of arc. STBS: Small target suppression test. STRDS: Small target random dot stereo test

114/36–60

Lang I stereotest Deka stereotest

254/preschool children

Simons et al. (1996)** [29] (USA)

Polaroid suppression test

201/60–71

Pott et al: (1998) [42] (Netherlands) Russmann et al. (1990)** [28] (Germany)

Lang II stereotest

1765/72–83

Computer-based random dot stereotest Random dot E test

Index test

Huynh et al. (2005) [41] (Australia)

176/36–48

No./agea included children

Study

Table 5 Characteristics of stereo acuity tests (cross-sectional studies)

Strabismus (cover test) + Refraction (noncycloplegic retinoscopy) + different test combinations Strabismus (cover test) + Refraction (photorefraction) + VA (HOTV or E test) TNO stereotest

VA (C test)

Strabismus (cover test) + VA (LogMar test) + Refraction (cycloplegic autorefraction)

Strabismus (cover test) + VA (Letter matching or Allen test)

Standard random dot stereotest

Reference testd

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thresholds defining reduced visual acuity, refractive errors or binocular disorders [e.g., 20–24, 27, 35, 38]. These findings indicate that despite considerable research work which has been carried out to investigate the development of the visual system [e.g., 44], the process of emmetropisation is still not understood. The fact that the performance of a vision screening test is dependent on the age of a child was also shown in the longitudinal study by Williams et al. [18]. In this study, sensitivity of individual tests or test combinations to detect amblyopia or conditions related to amblyopia increased with age, whereas specificity remained almost unchanged. However, it remains open whether this finding is more connected to visual changes during preschool years or to the difficulties involved in examining young children. Strengths and weaknesses of this systematic review A broad search strategy was applied to identify all relevant studies evaluating diagnostic accuracy of preschool vision screening tests. Studies were included if they examined children from the general population. We excluded studies which evaluated children with specific diseases or organic eye disorders. The reason for this was that evaluating a screening test in children with a high prevalence of visual disorders may overestimate diagnostic test accuracy [45]. Studies that reported only positive or negative predictive values were excluded. Similarly, we did not consider studies that evaluated only the feasibility and reliability of a screening test. Although these are important factors when choosing a screening strategy, in our view evaluating test accuracy is the first important step. However, the results of this systematic review show that diagnostic accuracy of preschool vision screening tests can only be investigated after establishing age-related values which define amblyopia, refractive errors and binocular disorders. Most of the studies evaluating diagnostic accuracy of preschool vision screening tests applied a cross-sectional design. We believe longitudinal studies are more appropriate to evaluate changes in visual acuity, refractive errors and binocular vision during the first 6 to 8 years of life. Other systematic reviews Similar to the findings of our review, a Cochrane review from 2005 recommends that a consensus needs to be

reached for the definition of amblyopia [46]. A recently published British health technology assessment (HTA) from 2008 concluded that the process of emmetropisation is not understood, and that much of what is known about vision development in children has been informed by animal studies [47]. Another review from 1999 found that there is a lack of high-quality studies and gold standards to identify children with amblyopia and its risk factors [48]. A French guideline from the year 2002 stressed that an ophthalmological examination is the only gold standard to identify children with visual impairments [49]. Diagnostic accuracy of the MTI photoscreener for the detection of visual anomalies in children was evaluated in a HTA from Spain [50]. This HTA concluded that more data about its safety, efficacy and efficiency need to be available before using this device in primary care. Despite the fact that other systematic reviews used different inclusion criteria, for example some reviews included studies examining high-risk children or studies including only children with a positive screening result in the gold standard examination, all reports agree that a consensus needs to be reached for the definition of amblyopia and its risk factors.

Implications for clinical practice and further research Studies evaluating diagnostic accuracy of preschool vision screening tests are complex because of two reasons: (1) there are at least three different target conditions of interest (reduced visual acuity, refractive errors and binocular disorders), and (2) the development of these visual impairments is not understood. We conclude that diagnostic test accuracy can only be sufficiently investigated after establishing age-related values defining amblyopia, refractive errors and strabismus. To address these questions, we recommend a longitudinal study design in which children are examined either with a single screening test (e.g., a tool to study refractive errors and strabismus without cycloplegia) or a combination of different tests at different ages (e.g., at 3, 4, 5 and 6 years of age). A comprehensive examination by an ophthalmologist which includes cycloplegic retinoscopy should be used as a “gold standard” in such studies.

Appendix Search strategy in Ovid: MEDLINE

1 2 3

Search term

Hits

exp CHILD/ exp INFANT/ (baby or babies or newborn or neonat$).mp.

1129108 692510 536032

Graefes Arch Clin Exp Ophthalmol (2009) 247:1441–1454

1451

Appendix (continued) Search term

Hits 49523 14438 3371 529317

16 17 18 19 20 21 22

exp schools/ exp CHILD-HEALTH-SERVICES/ exp CHILD-DAY-CARE-CENTERS/ (CHILD$ or ADOLESC$ or JUVENILE$ or MINOR$ or SCHOOL$ or KINDER-GARTEN$ or PRE?SCHOOL$ or NURSER$).ti. (CHILD$ or ADOLESC$ or JUVENILE$ or MINOR$ or SCHOOL$ or KINDER-GARTEN$ or PRE?SCHOOL$ or NURSER$).ab. 1 or 2 or 3 or 4 or 5 or 6 or 7 or 8 exp strabismus/ exp amblyopia/ exp REFRACTIVE-ERRORS/ ((EYE$ or SIGHT$ or VI-SION$ or VISUAL$) adj4 (PROBLEM$ or DEFECT$ or IMPAIR$ or DEFICI$ or REDUC$)).mp. [mp = ti, ot, ab, nm, hw] (LAZY adj EYE$).mp. [mp = ti, ot, ab, nm, hw] (AMBLYOPI$ or SQUINT$ or STRABISM$ or ANISO-METROPI$ or MYOPI$ or HYPERMETROPI$ or ASTIGMATI$ or AM-METROPI$ or HYPER-OPI$).mp. [mp = ti, ot, ab, nm, hw] cataract$.mp. microtropia.mp. glaucoma.mp. retinoblastoma.mp. ((heredit$ or retinal or macular) and dystroph$).mp. refract$.mp. [mp = ti, ot, ab, nm, hw] exp vision, low/

40130 75 36328 14353 5741 77398 936

23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40

(SPECTACLES or GLASSES).mp. exp Cataract/ 10 or 11 or 12 or 13 or 14 or 15 or 16 or 17 or 18 or 19 or 20 or 21 or 22 or 23 or 24 (test or tests or testing).mp. examination$.mp. ophthalmoscop$.mp. photoscreen$.mp. (acuity or red reflex).mp. exp Vision Tests/ or exp Visual Acuity/ exp Ophthalmoscopy/ (vision or visual).mp. (test$ or screen$).mp. 33 and 34 (Hirschberg or Bruckner or motil$ or funduscop$ or cyclopleg$ or skiascop$).mp. [mp = ti, ot, ab, nm, hw] (Auto?refract$ or random?dot or stereoacuity or Snellen or Sheridan–Gardiner).mp. [mp = ti, ot, ab, nm, hw] (Cover?uncover or alternate cover or corneal reflex or PhotoScreener or Visiscreen).mp. [mp = ti, ot, ab, nm, hw] (Retinomax or Suresight).mp. [mp = ti, ot, ab, nm, hw] 26 or 27 or 28 or 29 or 30 or 31 or 32 or 35 or 36 or 37 or 38 or 39

4495 16513 208688 1383219 424043 9356 95 46057 52117 5116 246181 2011737 58712 67108 2475 330 39 1844319

41 42 43 44 45 46 47 48 49

exp "Sensitivity and Specificity"/ exp Diagnosis/ diagnos$.mp. sensitiv$.mp. predict$.mp. accura$.mp. 41 or 42 or 43 or 44 or 45 or 46 9 and 25 and 40 and 47 exp Contact Lenses/

211681 3862053 1268941 743123 485857 238100 5133424 9851 8117

4 5 6 7 8 9 10 11 12 13 14 15

640000 2031820 9863 4081 17635 24836 14 32219

1452

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Appendix (continued) Search term

Hits

50 51 52 53 54 55 56 57 58 59 60 61

exp Eyeglasses/ (refractive adj correct$).ti. (refractive adj correct$).ab. ((optic$ or vision$ or visual$ or filter$ or lens$ or glass$ or spectacle$) adj3 (occlusion or penali$ or patch$)).ti. ((optic$ or vision$ or visual$ or filter$ or lens$ or glass$ or spectacle$) adj3 (occlusion or penali$ or patch$)).ab. 49 or 50 or 51 or 52 or 53 or 54 exp clinical trials/ exp research design/ comparative study/ or placebos.mp. exp treatment outcome/ double-blind method/ or single-blind method/ ((single or double or triple) adj blind$3).ti.

4478 29 316 129 671 12865 190907 212573 1341575 283315 98869 20568

62 63 64 65 66 67 68 69 70 71 72 73 74 75 76 77 78 79

((single or double or triple) adj blind$3).ab. random$.ti. random$.ab. controlled clinical trial.pt. clinical trial.pt. (clinical adj trial$1).ti. (clinical adj trial$1).ab. (control$3 adj trial$1).ti. (control$3 adj trial$1).ab. randomized controlled trial.pt. exp RANDOM ALLOCATION/ exp PROSPECTIVE STUDIES/ exp Follow-Up Studies/ 56 or 57 or 58 or 59 or 60 or 61 or 62 or 63 or 64 or 65 or 66 or 67 or 68 or 69 or 70 or 71 or 72 or 73 or 74 9 and 25 and 55 and 75 9 and 25 and 55 screen$.mp. exp Neonatal Screening/

78020 56160 364411 73779 450604 25698 90789 15725 38465 228874 57826 213531 332322 2474586 633 1765 287728 3723

80 81 82 83 84 85 86 87

exp VISION TESTS/ exp MASS SCREENING/ 78 or 79 or 80 or 81 9 and 25 and 82 48 or 76 or 83 48 or 77 or 83 (animals not human).sh. 85 not 86

19699 77069 309225 4644 10737 11540 4025575 11140

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