Sickle cell retinopathy (SCR), a common, potentially blinding eye condition found among some people with sickle cell disease, is caused by misshapen blood cells blocking blood vessels in the light-sensing retina. In a 10-year, retrospective study of adults with SCR treated at Wilmer Eye Institute, Johns Hopkins Medicine, researchers found active smoking is a strong modifiable risk factor for disease progression, highlighting smoking cessation and routine screening as two new, actionable means of preventing vision loss.
A finalized report on the study, published Aug. 22 in American Journal of Ophthalmology, is believed to be the largest United States-based longitudinal study of adults with sickle cell retinopathy that used modern medical tests and imaging to track the condition.
The researchers say their work helps clarify a long-suspected link between smoking and sickle cell retinopathy progression.
Beginning in early childhood, sickle cell retinopathy can affect anyone with sickle cell disease, but symptoms may not appear until later in life. Because of this, annual exams with a retina specialist are recommended for people with SCD from age 10 onward to catch SCR before vision is affected. The researchers say their findings reinforce the importance of these existing screening recommendations.
Adrienne Scott, M.D., study principal investigator and professor of ophthalmology at the Johns Hopkins University School of Medicine, says her team initiated the study to address an absence of modern data on risk factors for sickle cell retinopathy.
"Sickle cell retinopathy is severely understudied, and data is needed to create hypotheses to fund research that helps clinicians understand it," says Scott. "When we started our work, we realized even basic information, like SCR risk factors, couldn't be definitively stated. Because of this, we decided to determine them ourselves."
In the study, Scott and her team reviewed the health outcomes of 317 adults (620 eyes total) (mean age 35 years) with diagnosed sickle cell disease. All study participants had either non-proliferative sickle cell retinopathy - earlier stages of the disease involving retinal blood vessel changes (336 eyes) - or proliferative SCR, later stages of the disease marked by the growth of abnormal new blood vessels that can threaten vision (284 eyes).
All participants had been seen at Wilmer Eye Institute at least once between July 1, 2013, and June 30, 2023. Electronic medical records were used to confirm the sickle cell disease diagnosis of each participant and to determine whether and how SCR had worsened over time.
Reviewing the data, the researchers found about 1 in 10 eyes (36 eyes, or 10.7%) that were initially diagnosed with non-proliferative SCR progressed to proliferative SCR between follow-up appointments over eight years. Among eyes that already had proliferative SCR at the first visit, additional disease progression occurred in about 1 in 6 eyes (44 eyes, or 17%) over 11 years. The findings highlight the importance of consistent follow-up and retina exams for patients with SCR.
Comparing study groups, the researchers found people who actively smoked cigarettes or cigars at the time they were diagnosed with proliferative sickle cell retinopathy were nearly three times as likely to experience disease progression as nonsmokers with proliferative SCR (hazard ratio, 2.78). The researchers did not find a statistically significant association between disease progression and the other factors they examined, including age at diagnosis, sex, sickle cell disease genotype, hydroxyurea (sickle cell disease medication) use, blood transfusions, chronic red cell exchanges, bone marrow transplantation and lifetime smoking history.
The new findings, the research team says, suggest that current cigarette or cigar smoking may be more relevant to SCR progression than having smoked in the past.
"Smoking has been implicated in many different eye diseases, such as age-related macular degeneration, and we believe this is the first study showing a clear link between active smoking and sickle cell retinopathy progression. With this knowledge, clinicians and patients now have a direct and actionable means of preserving the patient's eye health," says Anshuman Agrawal, study lead author and medical student at the Johns Hopkins University School of Medicine.
The researchers caution that their study may include a greater proportion of people with severe SCR than would be seen in the general population, as the Wilmer Eye Institute is a specialty center known for providing advanced ophthalmology care.
Still, they say, a better understanding of risk factors for sickle cell retinopathy progression could help clinicians intervene earlier, while reassuring patients that an SCR diagnosis does not necessarily guarantee vision loss.
Additionally, understanding SCR may also help advance clinical understanding of other eye diseases that affect blood vessels in the eyes, such as diabetic retinopathy.
"I want to reassure people with sickle cell disease that, even with sickle cell retinopathy, they have a high chance of having normal vision for a long time. But treating sickle cell disease and attending regular retina exams is key to preserving sight, if it does develop," says Scott.
In addition to Agrawal and Scott, researchers who authored the study are Nur Cardakli, Wenqing Zhang, Uduak E. Obot and Anupam K. Garg.
The study authors have the following conflict-of-interest disclosures to share: Scott receives grant funding from Regeneron Pharmaceuticals, 4D Molecular Therapeutics and Genentech/Roche; consulting fees from EyePoint Pharmaceuticals, Adverum Biotechnologies, 4D Molecular Therapeutics, Genentech/Roche, Regeneron Pharmaceuticals, AbbVie/Allergan, Astellas Pharma and Apellis Pharmaceuticals; honoraria for lectures from Bayer, Boehringer Ingelheim, Alcon and Allergan/AbbVie; support for travel/meetings from Boehringer Ingelheim, Bayer and Alcon; and equipment/materials from Optos, Inc.
DOI: 10.1016/j.ajo.2026.07.026
