Meta-analysis Outlines Accuracy of Red Reflex Test

An abnormal red reflex finding most likely reflects an underlying ocular pathology in infants, but finding a normal red reflex during screening does not altogether exclude ocular disease, according to results of a meta-analysis published in JAMA Ophthalmology.

The American Academy of Pediatrics, the American Academy of Ophthalmology, and other organizations conclude that red reflex testing is an essential component of neonatal, infant, and child physical examination. Specifically, the test is used to ensure early detection of ocular diseases that could impair visual development such as retinoblastoma or congenital cataracts.

During the test, light reflection for the posterior segment of the eye is observed through an ophthalmoscope, making the pupil appear red. “Anything that blocks the passage of light through the eye will be observed as a duller red reflex, or the red reflex may be entirely blocked, making the pupil appear dark,” researchers wrote. “In addition, structural abnormalities of the posterior pole will change the reflection of light and can be detected during the examination.” Large refractive errors may also be observed as changes in the red reflex.

However, some conditions that the red reflex test aims to detect are very rare, meaning a large number of infants must be screened to detect those with disease. Congenital contacts have an annual incidence rate of 18 to 36 per 100,000 population, whereas retinoblastoma occurs in approximately 5 individuals per 100,000.

To provide insights into the test’s diagnostic accuracy, investigators conducted a systematic review and meta-analysis. Studies including consecutively screened infants aged less than 1 year who were not a priori diagnosed with a certain disease were eligible for inclusion. Eligible studies also used the red reflex test as the index test or the Brückner test, if it was used to identify ocular abnormalities.

After searching over 10 databases, researchers found 5 studies that were eligible for the qualitative and quantitative analyses. A total of 8713 unique participants were included in the prospective single-center studies. “All studies used the red reflex test without pupillary dilation and were compared with a reference test performed with pupillary dilation,” researchers wrote.

Analyses revealed:

• The prevalence of any ocular pathology in infants was estimated to be 27.3% (95% CI, 24.0%-30.9%).
• For any ocular pathology, an estimated sensitivity of 7.5% (95% CI, 7.4%-7.5%) and specificity of 97.5% (95% CI, 97.5%-97.5%) was found.
• Focusing on ocular pathologies that required a medical or surgical intervention, sensitivity improved to 17.5% (95% CI, 0.8%-84.8%) and specificity remained high at 97.6% (95% CI, 87.7%-99.6%).
• The rate of false-positive findings (ie, abnormal red reflex test result without underlying ocular abnormality) was 1.8%.
• The number of false-negative findings (ie, those infants with severe ocular disease who will be missed because of a normal red reflex test result) was 25.3%.
• The negative predictive value (NPV) of severe ocular disease was 99.2%, which means that 99 of 100 infants with a normal red reflex will have no ocular disease.
• The positive predictive value (PPV) of an abnormal red reflex was 7.7%, which means that the risk of severe ocular disease is increased more than 7-fold in these infants.

None of the studies included used pupil dilation for red reflex testing, as newborns and infants have smaller pupils, which may theoretically decrease the validity of the test.

Although important findings were occasionally missed by the test, real-life data clearly demonstrate that not performing red reflex screening will have detrimental effects on ocular health and visual outcomes, researchers concluded.

Reference

Subhi Y, Schmidt DC, Al-Bakri M, Bach-Holm D, and Kessel L. Diagnostic test accuract of the red reflex test for ocular pathology in infants: a meta-analysis. JAMA Ophthalmol. Published online November 12, 2020. doi:10.1001/jamaophthalmol.2020.4854