MANAGEMENT OF SICKLE CELL DISEASE

NIH Publication No. 02-2117. Revised May28, 2002 (Forth Edition) National Institutes of Health, National Heart, Lung, and Blood Institute. Download the entire PDF  file for Adobe   Click Here to return to Contents

Chapter 14 SICKLE CELL EYE DISEASE

Sickle cell vaso-occlusive events can affect every vascular bed in the eye, often with devastating visual consequences. Because early stages of sickle cell eye disease do not usually result in visual symptoms, the disease can go undetected unless a formal eye exam is performed by an ophthalmologist. The examination should include an accurate measurement of visual acuity, assessment of pupillary reactivity, careful evaluation of the anterior structures of the eye using a slit-lamp biomicroscope, and a thorough examination of the posterior and peripheral retina through a dilated pupil. This last examination should include fluorescein angiography. Patients with sickle hemoglobinopathies should have yearly eye examinations beginning in childhood and continuing through adulthood.

The clinical manifestations of sickle hemoglobinopathies are grouped according to the presence or absence of neovascularization in the eye. The distinction is clinically relevant because proliferation of new blood vessels on the retina is the key biological event that sets the stage for progression to vitreous hemorrhage and retinal detachment.

Non-neovascular ocular manifestations of sickle hemoglobinopathies include conjunctival vascular occlusions that transform smooth vessels into comma-shaped fragments, iris atrophy, retinal hemorrhages, retinal pigmentary changes, and other abnormalities of the retinal vasculature, macula, choroid, and optic disc. These clinical findings are readily apparent on dilated ophthalmoscopy, and all occur due to local vaso-occlusive events but rarely have visual consequences.

Progression to neovascularization or to the proliferative stage involves the growth of abnormal vascular fronds that place patients at risk of 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, such as vascular endothelial growth factor and basic fibroblast growth factor (1,2). Goldberg has defined five stages of proliferative retinopathy (3). 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, actual preretinal neovascularization occurs. The neovascular fronds typically assume a shape that resembles the marine invertebrate Gorgonia flabellum, known commonly as the "sea fan." Stage IV is defined by the presence of vitreous hemorrhage, and stage V is defined by the presence of retinal detachment. This last complication results from mechanical traction created by chronic, enlarging fibrovascular retinal membranes, with or without hole formation in the retina.

Although peripheral vaso-occlusion may be observed as early as 20 months of age (4), clinically detectable retinal disease is found most commonly between 15 and 30 years of age (5). Sickle retinopathy is found more often and earlier in SCD-SC, but is also common in SCD-SS and sickle thalassemia. Observational cohort studies have also shown that stages IV and V retinopathy occur more often in SCDSC subjects than in those with SCD-SS (6). It is a paradox that despite the less dramatic systemic consequences of their disease, subjects with SCD-SC and sickle thalassemia are more likely than SCD-SS patients to have serious ocular manifestations. Research has not been able to explain the reason for this profound discrepancy in the severity of the retinal and systemic manifestations among the various sickle hemoglobinopathies (see the introductory material and chapter 2, Neonatal Screening, for an overview of disease subtypes).

Diagnosis of proliferative retinopathy requires examination through a dilated pupil utilizing a wide-field indirect ophthalmoscope. Evaluation of retinal blood flow is performed with fluorescein angiography. Any patient identified with retinopathy should be followed by an ophthalmologist who specializes in diseases of the retina.

Treatment is reserved for eyes that have progressed to proliferative retinopathy, and patients are thus at risk for severe visual loss from bleeding and retinal detachment. Given the high rate of spontaneous regression and lack of progression of neovascularization in some eyes, the indications for treatment of retinal neovascularization are not always clear. 

Therapeutic intervention usually is recommended in cases of bilateral proliferative disease, spontaneous hemorrhage, large elevated neovascular fronds, rapid growth of neovascularization, and cases in which one eye has already been lost to proliferative retinopathy.

The goal is early treatment to induce regression of neovascular tissue before bleeding and retinal detachment occur. Techniques such as diathermy, cryotherapy and laser photocoagulation have been used to cause involution of neovascular lesions. Of all of these methods, laser photocoagulation has the fewest side effects.

If retinal detachment or nonclearing vitreous hemorrhage is present, surgical intervention is usually required. Surgical techniques include vitrectomy with or without the placement of a scleral buckle. Although modern vitreoretinal microsurgery can improve vision for many patients with advanced sickle retinopathy, it should be emphasized that surgery carries a significant risk of intraoperative and postoperative complications, including severe ocular ischemia, recurrent hemorrhage and elevated eye pressure (7). To minimize the risk of such complications, partial exchange transfusion has been recommended prior to surgery, usually with a target of about 50 to 60 percent normal red cells, although there has never been a controlled study demonstrating the efficacy of this maneuver (8).

INDICATIONS FOR URGENT OPHTHALMOLOGIC CONSULTATION

Immediate consultation with an ophthalmologist  familiar with the management of individuals with hemoglobinopathies is required for any individual with a sickle hemoglobinopathy, including sickle trait, who sustains eye trauma. Anterior segment trauma may result in hemorrhage into the anterior chamber of the eye, allowing sickled erythrocytes to clog the trabecular outflow channels and raise the intraocular pressure, producing glaucoma. In patients with sickle hemoglobinopathies, even a moderate increase in eye pressure may cause a significant reduction in perfusion of the optic nerve and retina, putting the eye at risk for ischemic optic atrophy and retinal artery occlusion. In such instances patients may require an emergent surgical washout of the anterior chamber.

Trauma considerations aside, any patient with a sickle hemoglobinopathy who has an acute change in vision should always be referred immediately to an ophthalmologist for a full evaluation.

Beginning in childhood, all patients with sickle hemoglobinopathies should have yearly dilated examinations by an ophthalmologist with expertise in retinal diseases. Any patient with a sickle hemoglobinopathy who experiences a change in vision should be referred for ophthalmologic consultation immediately.

Central retinal artery occlusion, an event which usually results in permanent, devastating loss of vision, is one of the few bona fide ophthalmic emergencies which demands intervention within minutes to hours after the onset of symptoms. Treatment consists of hyperoxygenation combined with rapid reduction of eye pressure utilizing surgical and medical techniques. Vision loss from hemorrhage or retinal detachment also calls for urgent care, but, unlike acute vascular occlusion, can be appropriately addressed within 24 to 48 hours. Any individual with a sickle hemoglobinopathy who sustains ocular or periocular trauma should be examined immediately by an ophthalmologist because of the increased risk of visual loss from elevated eye pressure associated with hemorrhage into the anterior chamber (hyphema).

1. Cao J, Mathers MK, McLeod DS, et al.Angiogenic factors in human proliferative sicklecell retinopathy. Br J Ophthalmol 1999;83:838-46.

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;71:649-55.

4. McLeod DS, Goldberg MF, Lutty GA. Dual perspective analysis of vascular formations in sickle retinopathy. Arch Ophthalmol 1993;111:1234-45.

5. Condon PI, Serjeant GR. Photocoagulation in proliferative sickle retinopathy: Results of a 5 year study. Br J Ophthalmol 1980;64:832-40.

6. Clarkson JG. The ocular manifestations of sickle cell disease: A prevalence and natural history study. Trans Am Ophthalmol Soc 1992;90:481-504.

7. Rednam KRV, Jampol LM, Goldberg MF. Scatter retinal photocoagulation for proliferative sickle cell retinopathy. Am J Ophthalmol 1982;93:594-9.

8. Charache S. Eye disease in sickling disorders. Hematol Oncol Clin North Am 1996;10:1357-62.

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Last modified: November 08, 2002