Project Summary
Sickle cell disease (SCD) causes vision-threatening ocular complications such as proliferative retinopathy. Risk
of sickle cell retinopathy increases with age, with some reports showing >60% of SCD patients having
proliferative retinopathy after age 40. It remains unclear how sickle cell trait (SCT), the heterozygous genotype
with one copy of the sickle cell mutation, may affect the eye. SCT, albeit assumed mild, is prevalent and
chronic. It affects 3 million Americans including ~8-10% of African Americans. It is known that under conditions
of stress or concomitant systemic diseases, SCT can become a pathologic risk factor for retinopathy. Evidence
has been accumulating to support that SCT can increase the risk of venous thromboembolism, ischemic stroke,
and glomerulopathy - conditions that have all been linked to an increased risk of retinopathy. These findings,
together with the increasing recognition of the role of ocular hemodynamics in various ocular diseases, support
a possible association between SCT and eye diseases/conditions. Because individuals with SCT have a
normal life expectancy, their vascular bed may accumulate damages from SCT as a result of repeated insults
over a long duration. We hypothesize that older individuals with SCT have an increased risk of eye diseases,
either alone or in conjunction with other known ocular risk factors (e.g., hypertension, diabetes). To test this
hypothesis, we propose an investigation nested within the African American Eye Disease Study (AFEDS), an
ongoing population-based study of 6,000 African Americans aged 40 years and older that has collected a large
amount of epidemiological, biological, and ocular data and biospecimens. Taking advantages of the unique,
existing resources of AFEDS, we propose to 1) identify the SCT status of 2,700 AFEDS participants who
donated samples of blood and retrospectively examine the associations between SCT and risk of ocular
diseases/conditions, and 2) acquire additional imaging data from ~216 individuals with SCT (432 eyes) using
advanced technologies (e.g. optical coherence tomography angiography, enhanced depth imaging of the
choroid, ultra-wide imaging of the retina, and conjunctival microcirculation imaging) and assess changes in
ocular structure, retinal microvasculature, and conjunctival hemodynamics due to SCT. As SCT is now
routinely detected in all US newborns and little is known about ocular complications associated with SCT, our
population-based study will fill an important knowledge gap. This timely investigation will provide valuable, new
data on how long-term exposure to SCT and associated vaso-occlusive events and hemolysis can alter ocular
microcirculation and structure. It will also inform us about how these events can contribute to vasculopathy in
other organs that share similar anatomical and physiologic properties with the eyes. Such knowledge will be
important contributors to the ongoing debate on health risk associated with SCT, and will help clinicians, public
health professionals, and policy experts allocate targeted healthcare and counseling services.