Purpose: To systematically review the evidence on screening for and treatment of amblyopia, its risk factors, and refractive error in children ages 6 months to 5 years.
Data Sources: PubMed/MEDLINE, the Cochrane Library, Cumulative Index of Nursing and Allied Health Literature, and trial registries through June 2016; reference lists of included articles and existing systematic reviews; outside experts; reviewers; and surveillance of the literature through June 7, 2017.
Study Selection: Two investigators independently selected English-language studies using a priori criteria. Eligible studies included randomized, controlled trials (RCTs) or prospective cohort studies with a concurrent control group that evaluated screening in children without known impaired visual acuity or obvious symptoms of impaired visual acuity; studies evaluating accuracy of screening tests compared with cycloplegic refraction or a comprehensive eye examination; RCTs of treatment compared with inactive controls; and controlled cohort or case-control studies assessing harms of screening or treatment.
Data Extraction: One investigator extracted data and a second checked accuracy. Two reviewers independently rated quality for all included studies using predefined criteria.
Data Synthesis: We included 40 studies; 34 evaluated test accuracy. No RCTs compared screening with no screening. One prospective cohort study (N=6,081) from the population-based Avon Longitudinal Study of Parents and Children (ALSPAC) compared screening at age 37 months with no screening among children who were routinely screened at ages 4 to 5 years (in both groups) and found no statistically significant difference for amblyopia prevalence at age 7.5 years for three different definitions of amblyopia (adjusted odds ratio, 0.63 [95% confidence interval (CI), 0.32 to 1.23] for interocular difference in acuity ≥0.2 logarithm of the minimum angle of resolution [logMAR], 0.72 [95% CI, 0.32 to 1.60] for interocular difference in acuity ≥0.3 logMAR, and 0.65 [95% CI, 0.38 to 1.10] for visual acuity in amblyopic eye 0.18 logMAR or worse). One RCT (N=3,490) from ALSPAC found about a 1 percent lower prevalence of amblyopia at age 7.5 years for intensive screening (at ages 8, 12, 18, 25, 31, and 37 months) compared with screening at age 37 months, although the difference was only statistically significant for one of two definitions of amblyopia (interocular difference in acuity ≥0.2 logMAR, 1.5% vs. 2.7%; relative risk, 0.55 [95% CI, 0.29 to 1.04]; interocular difference in acuity ≥0.3 logMAR, 0.6% vs. 1.8%; relative risk, 0.35 [95% CI, 0.15 to 0.86]).
Estimates for screening tests suggest utility for identifying children at higher risk for amblyopia risk factors or other visual conditions. Positive likelihood ratios were in the moderate range (5 to 10) for most studies, indicating that an abnormal result moderately increased the likelihood of target conditions. Most studies that evaluated combinations of clinical tests found high (>10) positive likelihood ratios. The largest study to directly compare multiple tests found similar accuracy across screening tests. Low testability rates may limit tests in children younger than age 3 years, especially clinical tests (e.g., visual and stereoacuity tests), but some data suggest that photoscreeners have high testability rates for younger children.
RCTs of treatment show that: 1) patching improves visual acuity of the amblyopic eye by an average of less than 1 line on the Snellen chart after 5 to 12 weeks among children with amblyopia risk factors pretreated with glasses, and more children treated with patching than with no patching experienced improvement of 2 or more lines (45% vs. 21%; p=0.003); 2) patching plus glasses improves visual acuity by about 1 line after 1 year (0.11 logMAR [95% CI, 0.05 to 0.17]) among children with amblyopia risk factors not pretreated with glasses; 3) glasses alone improve visual acuity by less than 1 line after 1 year (0.08 logMAR [95% CI, 0.02 to 0.15]) among children with amblyopia risk factors; and 4) the magnitude of improvement for patching plus glasses or glasses alone was greater among children with worse baseline visual acuity.
Few studies addressed potential adverse effects of screening. One prospective cohort study (N=4,473) from the ALSPAC project assessed school-age bullying by age 8 years among the subgroup of patched children; those screened in preschool had lower rates of bullying compared with those not screened in preschool. Screening tests are associated with high false-positive rates in low-prevalence populations; studies with a lower prevalence (<10%) of vision abnormalities showed much higher rates of false-positive results (usually >75%), while studies with a high prevalence had lower false-positive rates (usually <35%).
Limitations: No included studies evaluated school performance, functioning, or quality of life. The main limitation of the ALSPAC studies was high overall attrition (approximately 50%). Common methodological limitations of test accuracy studies included high (or not reported) rates of uninterpretable results or noncompliance with tests, unclear handling of uninterpretable results or noncompliance in analyses, lack of a representative spectrum of participants, and lack of a random or consecutive sample. Studies of test accuracy were most commonly conducted in Head Start programs, schools, the community, or ophthalmology clinics; primary care clinics were rarely involved. Applicability of findings to primary care settings is therefore less certain.
Conclusions: Studies that directly evaluated the effectiveness of screening were limited (because of study designs, attrition, imprecision, and quality) and do not establish whether vision screening in preschool-age children is better than no screening. Indirect evidence supports 1) the utility of multiple screening tests for identifying preschool-age children at higher risk for amblyopia risk factors or other visual conditions (most studies found that abnormal results moderately increased the likelihood of target conditions), and 2) the effectiveness of some treatments for improving visual acuity outcomes, although improvements were small, on average. Evidence on adverse effects of screening indicated a reduction in bullying and high false-positive rates in low-prevalence populations.