Investigation of Sickle Cell Retinopathy in Pediatric and Adolescent Patients Enrolled in a Large Cohort Study.

PURPOSE: Sickle cell disease results in vaso-occlusion and hemolysis, leading to ophthalmic and systemic complications. In the eye, these processes initiate retinal ischemia and neovascularization resulting in sickle cell retinopathy (SCR). Hydroxyurea therapy increases fetal hemoglobin (reducing ischemia), and chronic blood transfusions (CTXN) reduce strokes in children with abnormally high intracranial vessel velocities. It is not known if these treatments reduce retinopathy. Our hypothesis is that hydroxyurea and CTXN lower the risk of the development and slow the progression of retinopathy.

DESIGN

Using a large longitudinal cohort study, we determined the prevalence of SCR among pediatric and adolescent patients with sickle cell disease and the effects of disease-modifying therapy on reducing the prevalence and severity of sickle cell retinopathy.

PARTICIPANTS

We included all eye examinations of participants (age 10-18 at time of initial eye exam) at a single site from the Sickle Cell Research and Intervention Program cohort between October 2010 and September 2022. Patients without a dilated eye exam were excluded.

METHODS

At 10 years of age, yearly ophthalmologic assessments began for patients with hemoglobin SC disease and every other year for other sickle cell genotypes. Two ophthalmologists reviewed all 2237 eye examination results.

MAIN OUTCOME MEASURES: We obtained patient age, sex, sickle genotype, treatment received for sickle cell retinopathy, duration of exposure to sickle cell disease-modifying therapy, and hematologic indices (fetal hemoglobin and hemoglobin concentration) and abstracted data regarding SCR, severity grading, and treatment.

RESULTS

We observed that pediatric and adolescent patients with sickle cell disease receiving hydroxyurea therapy were 29% less likely to demonstrate SCR. Of those receiving hydroxyurea, 107 of 351 patients (30%) had SCR as compared with the 118 of 279 patients (42%) not receiving hydroxyurea (P = 0.0028). Patients receiving CTXN were 68% less likely to develop SCR. Of those, 20 of 121 patients (17%) had retinopathy as compared with the 205 of 509 patients (40%) not receiving CTXN (P < 0.001).

CONCLUSIONS

Our data from one of the largest cohorts of pediatric and adolescent patients with sickle cell disease support widespread use of hydroxyurea, CTXN, or both. We found that these therapies are associated with a smaller number of patients demonstrating SCR.

FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.