Sickle Cell Retinopathy: Clearing Up the Confusion
"Navigating the Terminology and Diagnosis for Better Outcomes"
A recent study by Beral and associates shed light on the prevalence of retinopathy and maculopathy in patients with sickle cell disease (SCD), noting the absence of a direct link to hematological parameters, blood rheology, or genotype. While this research contributes valuable insights, it also highlights the need for clear and consistent terminology in the diagnosis and classification of these conditions.
The retina, a complex structure essential for vision, is divided into the posterior pole and the peripheral retina. Within the posterior pole lies the macula, a critical area for central vision. General terms like 'retinopathy' and 'maculopathy' simply refer to diseases affecting the retina and macula, respectively. However, when dealing with specific conditions like sickle cell retinopathy (SCR), a more detailed approach is crucial.
Since Goldberg's classification of SCR in 1971, it has served as the gold standard for diagnosing and classifying the disease through funduscopic examination. Macular involvement in SCD was first described in 1972, with traction maculopathy already recognized as related to proliferative SCR. Maculopathy is, therefore, an integral component of SCR, closely linked to peripheral vascular nonperfusion.
Screening for Sight-Threatening Changes
Current sickle cell retinopathy screening focuses on detecting sea-fan neovascularization, the first sign of proliferative sickle cell retinopathy (PSR). If untreated, PSR can progress to vitreous hemorrhage or retinal detachment and cause severe visual impairment or blindness. Sickle cell retinopathy and maculopathy are frequent but underdiagnosed complications of sickle cell disease, and the cited review notes there is currently no ophthalmological follow-up protocol established as best for diagnosis and management.
OCT Expanded the View of Macular Disease
Proliferative sickle cell retinopathy has long been recognized as a major sight-threatening complication of sickle cell disease. With the development of spectral-domain optical coherence tomography (SDOCT), macular vascular abnormalities in people with sickle cell disease became commonly detectable. Sickle cell maculopathy is discussed as a distinct manifestation in this imaging-era literature, while a separate historical timeline traces sickle cell disease research from its first description in 1910 to gene therapy breakthroughs in 2023.
Retinopathy vs. Maculopathy: Defining the Terms in Sickle Cell Disease
The study by Beral and colleagues employs the terms 'Retinopathy' and 'Maculopathy' seemingly as distinct entities. However, the diagnostic criteria and classifications used for each were not clearly defined. This raises questions about how 'Retinopathy' (peripheral vascular alterations) and 'Maculopathy' (macular ischemic impairment) were specifically assessed, and what stage of peripheral retinopathy and OCT findings were considered for diagnosis.
- Fluorescein Angiography (FA): Detects peripheral SCR stages earlier.
- Optical Coherence Tomography (OCT): More sensitive for detecting sickle cell maculopathy.
Reviews Examine Imaging and Management
Recent reviews address several aspects of sickle cell eye disease. A 2026 review describes management options for non-proliferative and proliferative sickle cell retinopathy based on existing ophthalmic literature. A 2026 systematic review evaluates surgical outcomes for later stages using PRISMA 2020 guidelines, while another 2026 systematic review and meta-analysis examines OCT angiography measurements in sickle cell disease, with its literature search extending through July 2024.
Hemoglobinopathy Findings in Two Reports
The two cited reports describe different approaches to characterizing hemoglobin disorders. A capillary electrophoresis report identified eight cases of beta-plus thalassemia, featuring hemoglobin A2 above 4%, and three cases of hemoglobin C trait among patients with little to mild clinical manifestations and red blood cell indices suggesting anemia. A Nepalese population report collected all cases diagnosed positive for hemoglobinopathy through December 2018 from laboratory records at each site and analyzed them using SPSS version 20.0. The provided source details do not give comparable prevalence estimates, so they do not support a direct numerical comparison between the reports.
Moving Forward: Toward Enhanced Diagnostic Protocols
Clarifying the diagnostic criteria for retinopathy and maculopathy is crucial. Distinguishing between peripheral vascular changes and macular involvement is essential for accurate diagnosis and treatment planning.
Evidence Gaps and Surgical Outcomes
A scoping review mapped evidence on clinical and laboratory risk factors for sickle cell retinopathy and maculopathy, noting that screening is recommended but evidence for the optimal individual screening frequency is lacking. Separately, a systematic review of surgery reported that leave-one-out sensitivity analysis produced pooled SSAS estimates ranging from approximately 66% to 74%. Its discussion reports considerable gains in final visual acuity and anatomical success among patients undergoing surgery for sickle cell retinopathy.
Visual Impact and Patient Support
The Sickle Eye Project is described as a UK cross-sectional, non-interventional study of visual impairment due to sickle cell retinopathy and maculopathy. An optometry case study illustrates how bilateral inner retinal atrophy on macular OCT imaging, alongside a history of sickle cell disease, led clinicians to consider sickle cell maculopathy; other possibilities included bilateral artery occlusions, macular ischemia from diabetic retinopathy, and retinal atrophy after neuroretinitis. The Sickle Cell Retinopathy Network describes its work as advancing research, raising awareness of vision impacts, supporting patients, and fostering global research collaboration.
The Dell'Arti et al. study highlights the potential of OCT technology in identifying systemic risk factors associated with sickle cell maculopathy, and suggests that chronic chelation therapy and elevated HbF levels may offer protective benefits. This underscores the importance of continued research into both diagnostic and therapeutic strategies.
By refining diagnostic approaches and incorporating advanced imaging techniques, healthcare professionals can improve early detection and management of SCR and maculopathy, ultimately preserving vision and enhancing the quality of life for individuals with sickle cell disease.