Key Findings
- Purpose
To investigate the association between silent cerebral infarcts (SCI) and retinal ischemic injury detected by optical coherence tomography (OCT) in children and young adults with sickle cell disease (SCD), and to examine relationships between retinal and brain findings and clinical and hematologic markers. - Population (Model)
Single-center prospective case series involving 269 children and young adults with SCD, ages 4.4–21.9 years, evaluated at the Nemours Delaware Comprehensive Sickle Cell Research Center. All 269 participants underwent comprehensive ophthalmic examinations, including dilated funduscopy and retinal OCT. Among the 158 participants with HbSS or HbSβ⁰-thalassemia, 111 underwent brain magnetic resonance imaging (MRI) and magnetic resonance angiography (MRA) as part of clinical care. - Headline Result
Conventional funduscopic examination identified retinopathy in 14 of 158 participants with HbSS or HbSβ⁰-thalassemia (8.9%), whereas retinal OCT detected ischemic thinning in 106 (67.1%). Among the 111 participants who underwent brain MRI, 40 (36.0%) had brain MRI abnormalities consistent with SCI. Of these, 37 (92.5%) also had abnormal OCT findings. Among the 71 participants with normal brain MRI, 33 (46.5%) also had normal OCT findings. For MRI abnormalities consistent with SCI, OCT showed 93% sensitivity (95% CI, 84%–100%), 47% specificity (95% CI, 35%–58%), and a diagnostic odds ratio of 10.7. Participants with MRI abnormalities consistent with SCI showed more extensive retinal involvement, including greater bilateral involvement and thinning extending toward the foveal region. - Why It Matters
Brain MRI is currently the established imaging method used to detect silent cerebral infarcts. The strong association between retinal OCT abnormalities and MRI findings in this study suggests that OCT may have potential as a noninvasive prescreening tool for identifying children and young adults at higher likelihood of MRI abnormalities consistent with SCI. Its noninvasive nature and feasibility in children make OCT a candidate for further investigation. However, the study did not validate OCT-guided MRI referral, and OCT should not currently be used to exclude MRI.
- Evidence Gaps & Limitations
This was a single-center observational case series, and MRI/MRA was available for only 111 of the 158 participants with HbSS or HbSβ⁰-thalassemia. Brain imaging was obtained as part of clinical care, which may introduce selection bias. The study does not establish whether retinal OCT abnormalities precede cerebral injury, predict future SCI, track progression, respond to treatment, or improve clinical outcomes. The relatively low specificity also means that abnormal OCT findings cannot yet reliably identify which participants have MRI abnormalities consistent with SCI without confirmatory brain imaging. Larger, multicenter prospective studies are needed to validate OCT performance and determine whether it has clinical utility for prescreening or monitoring.
Source: Journal of Sickle Cell Disease- “Retinal Optical Coherence Tomography as a Noninvasive Biomarker of Silent Cerebral Infarcts in Pediatric Sickle Cell Disease”
Regulatory & Guideline Watch
The 2020 American Society of Hematology (ASH) guideline on cerebrovascular disease in SCD recommends at least one brain MRI without sedation in early-school-age children with HbSS or HbSβ⁰-thalassemia to detect silent cerebral infarcts. For children ages 2–16 years with these genotypes, ASH also recommends annual transcranial Doppler (TCD) screening for stroke risk. When an infarct-like lesion consistent with SCI is identified, ASH recommends neurological evaluation, assessment for cognitive or functional effects, and discussion of secondary prevention with the patient and family. MRI surveillance every 12–24 months is recommended to assess for progression. The guideline also identifies improved imaging strategies for identifying children at higher risk of cerebral infarction as an area for further research. Retinal OCT is not established in the cited ASH guideline as a replacement for brain MRI or TCD for cerebrovascular screening.