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.
Treatment
The primary goal of proliferative sickle retinopathy treatment is to minimize or eliminate neovascularization because vitreous hemorrhage and retinal detachment account for most visual loss in hemoglobinopathies. Vision loss prevention is contingent on early detection and treatment of proliferative sickle cell retinopathy. Visual loss is believed to be predominantly a complication of perfused proliferative sickle cell retinopathy. To better define the place of treatment, identification of the determinants of autoinfarction is required, but identification of patients whose proliferative sickle cell retinopathy is likely to proceed to visual loss is of greater importance. Although surgical treatment is not indicated for stage I and II disease, most advocate treatment of sickle retinopathy for stage III disease 4. The most commonly-used therapeutic modalities for this condition include laser retinal photocoagulation, retinal cryotherapy, and vitrectomy.
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.
References
1. Penman AD, Serjeant GR. Recent advances in the treatment of proliferative sickle cell retinopathy. Curr Opin Ophthalmol 1992;3:379-88.
2. Aiello LP. Clinical implications of vascular growth factors in proliferative retinopathies. Curr Opin Ophthalmol 1997;8:19-31.
3. Goldberg MF. Classification and pathogenesis of proliferative sickle retinopathy. Am J. Ophthalmol 1971;71:649-65.
4. Charache S. Eye disease in sickling disorders. Hematol Oncol Clin North Am 1996;10:1357-62.
5. Morel C. [Retinal involvement in hemoglobinopathy]. J Fr Ophtalmol 2001;24:987-92.
6. Spires R. Ocular manifestations of sickle cell disease. J Ophthalmic Nurs Technol 1995;14:74-7.
7. Fany a, Boni S, Adjorlolo C, et al. [Retinopathy as a sickle-cell trait: myth or reality?]. J Fr Ophtalmol 2004;27:1025-30.
8. Nia J, Lam WC, Kleinman DM, Kirby M, Liu ES, Eng KT. Retinopathy in sickle cell trait: does it exist? Can J. Ophthalmol 2003;38:46-51.
9. Kehinde MO, Akinsola FB. Ocular findings in sickle cell disease patients in lagos. Niger Postgrad Med J. 2004;11:203-6.
