Proliferative Sickle Cell Retinopathy

Proliferative sickle cell retinopathy (PSR) occurs most commonly with sickle cell hemoglobin C (SC), at a rate of approximately 33%. It occurs less commonly with sickle cell thalassemia (SThal), at a rate of approximately 14%. Sickle cell homozygote (SS) disease results in more systemic complications but has a very low incidence of proliferative retinopathy, approximately 3%. Proliferative retinopathy is rare with sickle cell trait (AS). The ocular complications result from ischemia secondary to infarction of the retinal tissue by means of arteriolar, precapillary arteriolar, capillary, or venular occlusions; they include retinal neovascularization, preretinal or vitreous hemorrhage, and tractional retinal detachment.

PSR has been classified into 5 stages based on the following pathogenetic sequence:

1. Peripheral arteriolar occlusions (stage 1) lead to peripheral nonperfusion and

2. peripheral arteriovenular anastomoses (stage 2), which are dilated, preexisting capillary channels.

   Figure 7-2 Retinal arteriolar occlusions in nonproliferative sickle cell retinopathy (NPSR). A, Color fundus photograph of patchy parafoveal creamy retinal infarctions in the left eye of a 21-year-old woman with sickle cell (Hb SS) disease; the sickling crisis was dehydration-induced. B, Fluorescein angiogram demonstrates occlusion of multiple small retinal arterioles (arrows); however, none correspond to the areas of opacified retina. Similar findings were present in the other eye. The patient maintained good central visual function. C, Optical coherence tomography (OCT) demonstrates hyperreflectivity in the middle retina corresponding to an area of creamy retinal infarction, suggesting ischemia of the intermediate and deep capillary plexus. There is temporal retinal thinning with loss of the inner retinal layers, indicating previous infarctions in that area.

   

   (Courtesy of Michael Dollin, MD.)

3. Preretinal sea fan neovascularization (stage 3) may occur at the posterior border of areas of nonperfusion and lead to

4. vitreous hemorrhage (stage 4) and

5. tractional retinal detachment (stage 5).

PSR is one of many retinal vascular diseases in which extraretinal fibrovascular proliferation occurs in response to retinal ischemia. Whereas the neovascularization in eyes with proliferative diabetic retinopathy (PDR) generally begins postequatorially, the neovascularization in PSR is located more peripherally (Fig 7-4). Another way in which PSR can be differentiated from PDR is that in PSR, spontaneous regression of the peripheral neovascularization by autoinfarction frequently occurs, resulting in a white sea fan neovascularization (Fig 7-5). Table 7-2 presents a differential diagnosis of peripheral retinal neovascularization.

• Elagouz M, Jyothi S, Gupta B, Sivaprasad S. Sickle cell disease and the eye: old and new concepts. Surv Ophthalmol. 2010;55(4):359–377.

Figure 7-3 Bilateral, multiple branch retinal artery occlusions (BRAOs) in NPSR. A, Fundus photographs show multiple acute BRAOs (arrows) in a 5 ½-year-old boy with Hb SS during a massive sickling episode. B, Fluorescein angiography images show numerous medium and large arteriolar vessel occlusions. C, The patient was treated promptly with a hypertransfusion protocol, which resulted in dramatic reperfusion of the retina. However, the corrected distance visual acuity did not improve beyond 20/200 in either eye.

(Courtesy of Brian Leonard, MD.)

Figure 7-4 Wide-field fundus montage images of the left eye of a 26-year-old African American man with a history of sickle cell hemoglobin C (SC) disease. A, Hemorrhaging has occurred at the anterior border of the proliferative lesions. B, The wide-field montage fluorescein angiogram shows leakage from the sea fan lesions in the periphery and peripheral nonperfusion anterior to the sea fans.

(Courtesy of Asheesh Tewari, MD.)

Figure 7-5 Fundus photograph of peripheral neovascularization (sea fan neovascularization) with autoinfarction, as illustrated by the white atrophic vessels.

(Courtesy of Harry W. Flynn, Jr, MD.)

Table 7-2 Differential Diagnosis of Peripheral Retinal Neovascularization

Excerpted from BCSC 2020-2021 series: Section 10 - Glaucoma. For more information and to purchase the entire series, please visit https://www.aao.org/bcsc.