Pathophysiology and treatment of proliferative sickle cell retinopathy

Sickle Cell Retinopathy

Sickle cell hemoglobinopathy encompasses a group of inherited genetic disorders, which cause erythrocytes to sickle and adversely affect multiple organ systems. The sickled erythrocytes lead to microvascular occlusion, which affects the peripheral retinal vasculature and results in retinal ischemia and development of proliferative sickle cell retinopathy. If this series of events does not stabilize or reverse, the end-stage results may be retinal infarction and/or detachment 1.

Pathophysiology

Non-proliferative ocular outcomes of sickle hemoglobinopathies include conjunctival vascular occlusions that lead to irregularities of the smooth vessels. These findings are apparent on dilated ophthalmoscopy and occur due to local vasoocclusive events. Visual side effects are rare.

Progression to the proliferative stage involves growth of abnormal vascular fronds, which predispose to vitreous hemorrhage and retinal detachment. The initiating event in the pathogenesis of proliferative disease is thought to be peripheral retinal arteriolar occlusions. Local ischemia from repeated episodes of arteriolar closure is presumed to trigger angiogenesis through the production of endogenous vascular growth factors 2.

Sickle cell retinopathy progresses through five stages, which are defined below 3:

Stage I: Peripheral arteriolar occlusions

Stage II: Peripheral arterio-venular anastomoses

Stage III: Neovascularization

Stage IV: Vitreous hemorrhage

Stage V: Retinal detachment

In stage I, peripheral arteriolar occlusion is present. In stage II, vascular remodeling occurs at the boundary between perfused and nonperfused peripheral retina with the formation of arteriovenous anastomoses. In stage III, pre-retinal neovascularization occurs. The neovascular fronds typically assume a shape that resembles the marine invertebrate Gorgonia flabellum, known more commonly as the "sea fan" 2. Stage IV is defined by the presence of vitreous hemorrhage, and stage V is defined by the presence of retinal detachment, which results from mechanical traction created by chronic, enlarging fibrovascular retinal membranes, with or without hole formation in the retina.

Laser photocoagulation

Laser retinal photocoagulation is the most common treatment for proliferative sickle cell retinopathy 5. Variations of this technique include scatter photocoagulation and feeder vessel photocoagulation. Scatter photocoagulation is efficacious in the treatment for sea fan lesions. The desired outcome of this therapy is extraretinal fibroneovascular tissue regression. Localized scatter photocoagulation treats early proliferative changes. Once neovascularization invades the vitreous, localized scatter photocoagulation is generally less effective. If this technique does not result in regression of proliferative changes, feeder vessel photocoagulation may be used as an adjunct to induce infarction to the remaining sea fans.

Feeder vessel photocoagulation

Obliterating feeder vessels by retinal photocoagulation causes infarction of peripheral neovascular beds. This technique manages proliferative sickle retinopathy effectively, especially in cases where neovascularization persists after extensive scatter photocoagulation treatment 6. Feeder vessel photocoagulation is often complicated by vitreous hemorrhage, retinal detachments, choroidal ischemia, choroidal neovascularization, subretinal hemorrhage and/or fibrosis, or macular pucker and hole formation.

Retinal cryotherapy

Retinal cryotherapy is useful in treating peripheral retinal ischemia as opposed to directly obliterating these neovascular beds. This methodology of "indirect" obliteration of the neovascular bed results in regression of abnormal vessels with minimal complications. Cryotherapy often is limited to cases with cloudy ocular media.

Vitrectomy

Vitrectomy is indicated in cases of nonresolving vitreous hemorrhage and retinal detachment (stages IV and V). This procedure relieves the internal tractional forces that act on the retina and facilitate retinal photocoagulation. Complications associated with vitreoretinal surgery are anterior segment ischemia, sickling crisis, optic nerve, and macula infarctions.

Summary

Sickle cell disease is a genetic disorder that manifests itself in all body systems. Although some authors have questioned whether retinopathy is actually a sickle cell trait 9. Surgical treatment is indicated once retinopathy advances to the proliferative stage. Several treatment options may be utilized, but should be chosen to meet the patient's medical history and disease severity.