Research Summary

Active Smoking Linked to Sickle Cell Retinopathy Progression

Ashton L. Stahl

Key Highlights

  • Progression occurred in 10.7% of eyes with baseline nonproliferative disease over a median of 7.8 years.
  • Among at-risk eyes with baseline proliferative disease, 17% progressed over a median of 11.1 years.
  • Active smoking at proliferative disease diagnosis was associated with progression (HR, 2.78; 95% CI, 1.50–5.16).
  • Qualitative macular optical coherence tomography findings were not associated with progression.

Active smoking at the diagnosis of proliferative sickle cell retinopathy (PSR) was significantly associated with subsequent progression to more advanced disease, according to a retrospective cohort study published in the American Journal of Ophthalmology. The study evaluated long-term progression in both nonproliferative and PSR and identified factors associated with worsening disease.

Described as the largest longitudinal study evaluating sickle cell retinopathy progression, the investigation focused on 620 eyes in 317 patients. Participants presented at least once to the Retina Division of the Wilmer Eye Institute between July 1, 2013, and June 30, 2023.

Researchers retrospectively extracted demographic information and clinical histories from electronic medical records. They used fluorescein angiography or ultra-widefield fundus photography to classify retinopathy according to Goldberg staging and Cox proportional hazards models to evaluate factors associated with progression. The main outcomes were progression from baseline nonproliferative to proliferative retinopathy and from baseline proliferative retinopathy to more advanced proliferative disease.

Study Findings

Progression to proliferative sickle cell retinopathy occurred in 10.7% of eyes with nonproliferative disease at baseline during a median follow-up of 7.8 years. Among at-risk eyes with proliferative disease at baseline, 17% progressed to more advanced proliferative disease during a median follow-up of 11.1 years. Active smoking at proliferative retinopathy diagnosis was significantly associated with subsequent progression, with a hazard ratio of 2.78 (95% CI, 1.50–5.16).

The study noted that progression of sickle cell retinopathy was not associated with age at diagnosis, sex, genotype, hydroxyurea use, blood transfusions, chronic red cell exchanges, bone marrow transplantation, or lifetime smoking history.1 Furthermore, qualitative assessment of macular optical coherence tomography findings did not correlate with baseline peripheral vascular stage and also was not associated with subsequent retinopathy progression.

Clinical Implications

According to the study authors, the higher progression rate in the baseline proliferative retinopathy cohort supports early referral and longitudinal ophthalmic surveillance for these patients.1 They emphasize continued ophthalmic follow-up among patients who already have proliferative disease.

The authors also stated that the strong association between active smoking at proliferative retinopathy diagnosis and subsequent progression supports smoking cessation recommendations. For active smokers with proliferative retinopathy, they additionally support closer monitoring with timely intervention.

Expert Commentary

“The higher progression rate within the baseline PSR cohort supports early referral and longitudinal ophthalmic surveillance for these patients,” the researchers concluded.

Reference

Agrawal A, Cardakli N, Zhang W, Obot UE, Garg AK, Scott AW. Predictive factors for progression in sickle cell retinopathy: longitudinal evaluation of a United States cohort. Am J Ophthalmol. 2026 Nov;291:282-291. doi: 10.1016/j.ajo.2026.07.026. Epub 2026 Jul 20. PMID: 42476435.