Male Sex, Younger Age Linked to Sickle Cell Retinopathy Progression

A large single-center retrospective cohort study identified low rates of progression from non-proliferative sickle cell retinopathy (NPSR) to proliferative sickle cell retinopathy (PSR), while nearly 1 in 5 eyes with PSR progressed to a more advanced level during follow-up.

Cox proportional hazard models constructed to evaluate patient- and disease-specific factors associated with the risk of progression to worsening stages of PSR revealed no queried factors achieved statistical significance at the P = .05 level. These data were presented at the American Society of Retina Specialists (ASRS) 42nd Annual Meeting.

Male sex and younger age at the final visit were each linked to a raised risk of progression within PSR, while notable factors, including genotype and current or prior use of hydroxyurea, demonstrated no significant impact on the risk of progression.

“While univariate and multivariate analyses did not reach statistical significance, male sex and younger age at last follow-up visit trended towards an association with higher risk of progression,” wrote the investigative team, led by Anupam K. Garg, MD, PhD, Wilmer Eye Institute.

Sickle cell retinopathy is an inherited hemoglobinopathy that can present as either NPSR or PSR, depending on the presence of vascular proliferation. PSR is more likely to lead to irreversible vision loss. This retrospective review involved all patients with PSR observed by the retina service at Wilmer Eye Insitute between July 2013 and June 2023.

Clinical evaluation by a retina specialist was used to determine the disease stage, including a review of available retinal imaging, including optical coherence tomography (OCT), fluorescein angiography, and fundus photography. Endpoints included the proportion of patients who progressed from NPSR to PSR and the proportion of patients who progressed to a worse stage of PSR.

A total of 187 eyes from 103 subjects were identified (41.7% male), with a median follow-up of 6.1 years. Evaluation of hemoglobinopathy showed approximately 67% of patients had the HbSC genotype, 25.2% had the HbSS genotype, and 7.8% had other variants.

Analysis of disease-modifying therapy use revealed that 23.3% of patients received hydroxyurea treatment and 14.6% received chronic exchange transfusions.

Of the population, 13 (7.0%) eyes were initially noted to have NPSR at a prior visit and progressed to PSR during the follow-up. Meanwhile, 35 (18.7%) eyes progressed to a more advanced stage of PSR during the follow-up period—71% of these eyes were HbSC and 26% were HbSS.

Cox proportional hazards models revealed no patient- or disease-specific factors were statistically significantly associated with the risk of progression to worsening stage of PSR at the P <.05 level.

Upon analysis, male participants had a higher PSR progression risk than female participants (hazard ratio [HR], 1.93 [95% CI, 0.98 - 3.81]; P = .059), while older age at final visit was associated with a decreased risk of progression (HR, 0.98 [95% CI, 0.95 - 1.01]; P = .15).

On the other hand, patient factors, including genotype, age at initial presentation of PSR, ocular and systemic comorbidities, use of hydroxyurea, history of chronic exchange transfusions, anticoagulation use, and fellow eye without PSR, did not reach statistical significance.

Garg and colleagues noted the multivariate analysis including all factors with P ≤ .2 did not explain the findings as well as gender alone (P = .11 versus P = .06). Length of follow-up was remarkably varied, with approximately 25% of patients with ≤1 year of follow-up between the initial clinic visit with diagnosis of PSR and the final follow-up visit.

“Work is in progress to develop a comprehensive database of all patients seen with sickle cell retinopathy (proliferative and non-proliferative) over a 10-year period and utilize machine learning to develop predictive models to help identify risk factors for progression to proliferative sickle cell retinopathy,” they wrote.

Reference

_{Garg AK. Identification of Risk Factors Associated With Development or Progression of Proliferative Sickle Cell Retinopathy. Poster presented at the American Society of Retina Specialists (ASRS) 42nd Annual Meeting. Stockholm, Sweden. July 17-20, 2024.}