Keeping an Eye Out for Sickle Cell Retinopathy

Sickle cell disease (SCD) is one of the most common inherited hemoglobinopathies. The disease affects approximately 100 000 Americans, with a predominance in African American, Asian, and Mediterranean ancestry.¹ Autosomal recessive mutations of the beta globin subunit for hemoglobin alter the protein structure, making erythrocytes more susceptible to intravascular deformation, especially in a hypoxic environment.² Erythrocyte “sickling” occurs as they elongate and become rigid yet fragile to damage, leading to potential vascular occlusion, injury, and distal ischemia.²

Several disease subtypes exist depending on mutation location and whether the faulty gene is inherited from one parent or both. Inheritance of this gene from both parents results in sickle-cell anemia (HbSS). There are several heterozygous forms of SCD, including sickle-hemoglobin C disease (HbSC) and sickle beta-thalassemia (SThal).³

A common complication of this systemic disease is the vision-threatening manifestations of sickle cell retinopathy.⁴ The most critical genotypes concerning ophthalmic manifestations include HbSC and SThal, which account for 33% and 14% incidence of proliferative sickle cell retinopathy, respectively,⁵ with HbSC portending a worse prognosis.³

Pathophysiology of sickle cell retinopathy

Changes in retinal vascular damage in individuals with sickle cell disease are called sickle cell retinopathy. Vascular occlusion and diminished blood flow through the retina and choroid may prompt retinal thinning and progressive neovascularization,⁶ potentially leading to irreversible vision loss.⁶ More advanced forms of sickle cell retinopathy can also present as vitreous hemorrhage and retinal detachment; therefore, frequent screening and prompt treatment are imperative for vision conservation.

Sickle cell retinopathy is classified as non-proliferative or proliferative, the latter of which is further subtyped via the Goldberg classification system.

Sickle cell classifications

Non-proliferative sickle cell disease (NPSCD) does not involve vascular proliferation, unlike proliferative sickle cell disease (PSCD), which occurs in the ischemic [usually peripheral] retina. Low oxygen concentration in PSCD leads to autocrine production of angiogenic factors and thus neovascularization.²

Goldberg classification further grades proliferative sickle disease severity into five stages.⁶

Proliferative Sickle Cell Disease (PSCD) stages include:

Peripheral arterial occlusion
Peripheral arteriovenous anastomoses
Neovascularization and fibrous proliferation, rendering the characteristic “sea fan” shape
Vitreous hemorrhage
Tractional retinal detachment

Differential diagnosis

Sickle cell retinopathy should be differentiated from other pathologies that may lead to similar retinal changes and findings. Although a prior diagnosis of SCD can help guide an assessment, it is important to consider the differential diagnoses that can elicit a similar presentation or co-occur with sickle cell retinopathy.^3,4 This includes, but is not limited to, diabetic retinopathy, retinal vascular occlusion, sarcoidosis, retinopathy of prematurity, hypertensive retinopathy, ischemic retinopathy, infectious retinopathy, hyperviscosity syndrome, chronic myelogenous syndrome, retinitis pigmentosa as well as radiation retinopathy.^3,4

Diagnosis and workup of sickle cell retinopathy

SCD retinopathy is mainly a clinical diagnosis based on critical signs and symptoms. Retinal involvement due to sickle cell disease may go unnoticed unless the patient is symptomatic.

However, when symptoms present, it is vital to be aware of common complaints:⁶

Eye pain
Blind spots
Floaters
Flashes
Decreased visual acuity
Increased light sensitivity
Double vision
Loss of peripheral vision

Non-neovascular signs include hemorrhage and location determine key characteristics observed: intraretinal hemorrhages have a “salmon patch" appearance whereas subretinal hemorrhages have a "black sunburst" appearance. Neovascular signs include “sea fanning,” which can cause vitreous hemorrhage, retinal breaks, and tractional retinal detachment.⁵

Treatment

Essential treatment includes targeting the systemic disease first and then following through with imperative ophthalmologic screening and treatment. Currently, there is no therapy for non-proliferative sickle cell retinopathy,³ but patients should be seen by their ophthalmologist approximately every 6 months.⁵

Although there is no standard protocol for proliferative sickle cell retinopathy, the overall theme for treatment is to prevent neovascularization and subsequent retinal detachment and vitreous hemorrhage.⁴ Observation is indicated for small areas of abnormal vessel growth because often, these subside without treatment.² Larger areas of abnormal vessel growth require laser photocoagulation, as these are more prone to anterior segment ischemia.^2,5,6 Scatter laser is effective and safe for sea fanning.³

Additionally, like photocoagulation to ischemic areas, vascular endothelial growth factor inhibitors and fibroblast growth factor inhibitors effectively achieve regression of neovascularization.^3,6 They further prevent the release of endothelial growth factors^3,6 and thus decrease PSCD complications.

In the unfortunate circumstance of vitreous hemorrhage or retinal detachment, a surgical approach is taken.^3,5 During the pars plana vitrectomy, key considerations need to be taken into account to prevent anterior segment ischemia.^3,5 These include using local anesthetics without epinephrine, avoiding disinsertion of extraocular muscles (or more than 1 or 2), adequate hydration, oxygenation, and avoidance of encircling scleral buckles.^3,5

To prevent further retinal infarction, it is recommended to ensure intraocular pressure is in the low-to-normal range during the procedure.³

Screening

Frequent retinal screening, monitoring, and proper treatment are imperative for visual conservation in individuals affected by SCD. Per the American Academy of Ophthalmology guidelines, it is recommended that patients with sickle cell disease have dilated funduscopic examinations every 1-2 years, beginning at age 10, and preferably by a retina specialist.⁴

Coding

Per the International Classification of Diseases (ICD) nomenclature,⁷ sickle cell retinopathy is recognized by the ICD-10-CM diagnosis code H36.⁷ Identifying synonyms include: proliferative retinopathy due to sickle cell disease, retinal dystrophy, retinal dystrophy due to systemic disorder, retinal dystrophy in cerebrospinal lipidoses, sickle cell proliferative retinopathy, sickle cell retinopathy, and sickle cell retinopathy (eye condition).⁷

Conclusions

The above guide to sickle cell retinopathy is a brief overview of the background, pathophysiology, common patient complaints, diagnosis, and treatment of sickle cell retinopathy. Sickle cell disease is one example of how multidisciplinary teams—such as ophthalmologists, cardiologists, hematologists, and primary care physicians—collaborate to treat disease manifestation in multiple organ systems. For ophthalmologists, the central focus is preventative to inhibit neovascularization, hemorrhage, and retinal detachment.

References

Complications and Treatments of Sickle Cell Disease | CDC. Published December 2020. Accessed January 22, 2022. https://www.cdc.gov/ncbddd/sicklecell/treatments.html#VisionLoss
John T. Thompson M. Sickle Cell Retinopathy - Patients - The American Society of Retina Specialists. The Foundation of the American Society of Retina Specialists. . Published 2020. Accessed January 22, 2022. https://www.asrs.org/patients/retinal-diseases/41/sickle-cell-retinopathy
Vinay A. Shah M.D, Deepak Sambhara M, Peter Bracha M, Harikrishnan Vannadil MM, Jason Hsu M, Jennifer I Lim MD. Sickle Cell Retinopathy - EyeWiki. American Academy of Opthalomology. Published November 14, 2021. Accessed January 22, 2022. https://eyewiki.aao.org/Sickle_Cell_Retinopathy#Disease_Entity
Mashal Akhter M, Michelle W. Latting M, and Adrienne W. Scott M. Management of Proliferative Sickle Cell Retinopathy. EyeNet - Am Acad Ophthalmol. Published online October 2018.
Prashant K. Parekh MM, Matthew A. Miller M, Stephen R. Russell M. Sickle Cell Retinopathy. EyeRounds.org. Published April 6, 2016. Accessed January 22, 2022. https://webeye.ophth.uiowa.edu/eyeforum/cases/233-Sickle-Cell-Retinopathy.htm
Menaa F, Khan BA, Uzair B, Menaa A. Sickle cell retinopathy: improving care with a multidisciplinary approach. J Multidiscip Healthc. 2017;10:335. doi:10.2147/JMDH.S90630
The Web’s Free 2022 ICD-10-CM/PCS Medical Coding Reference. Accessed January 22, 2022. https://www.icd10data.com/