SICKLE CELL DISEASE

SIGNS AND SYMPTOMS
Ocular symptoms are uncommon in the early stages of the disease. Systemically, symptoms include painful crises of abdominal and musculoskeletal discomfort.

Ocular signs include comma-shaped vessels in the bulbar conjunctiva, iris atrophy, iris neovascularization, dull-gray fundus appearance, retinal venous tortuosity, nonproliferative retinal hemorrhages in the subretinal, intraretinal or preretinal position. Further signs include black sunbursts (retinal pigment epithelial hyperplasia secondary to deep retinal vascular occlusions), glistening refractile deposits in the retinal periphery (hemosiderin-laden macrophages), salmon patch hemorrhages (orange-pink-colored intraretinal hemorrhage), angioid streaks (breaks in Bruch's membrane radiating from the optic nerve), venous occlusion, artery occlusion, peripheral neovascularization (seafan retinopathy) with subsequent vitreous hemorrhage and tractional retinal detachment.


PATHOPHYSIOLOGY
Hemoglobinopathies are among the more commonly inherited diseases in humans. Hemoglobinopathies result when there is altered structure, function or production of hemoglobin. Hemoglobin is the principle protein of the erythrocyte, responsible for binding and facilitating oxygen transmission to tissues. In the four variations of sickle cell disease, systemic and ocular tissues become deprived of oxygen and undergo pathologic changes.

Normal erythrocytes, containing normal hemoglobin, appear as flexible, pliable, biconcave discs. Erythrocytes affected by sickling disease lose their biconcave shape and their ability to efficiently move through the circulatory system. The "sickled" cells become rigid, restrict blood flow, produce clots and cause tissues to become hypoxic.

Variations in the alteration of the amino acid sequence on the globin chain produce variations in the disease's expression. The four forms of the disease are often referred to by their genotype: sickle cell trait (AS), sickle cell anemia (SS), sickle cell disease (SC) and sickle cell thalasemia (SThal).

Systemically, the sickle cell anemia variation (SS) produces the most symptoms. With respect to the eye, the sickle cell disease mutation (SC) produces the most effects. Overall, the sickle cell trait expression (AS) produces the fewest complications.

MANAGEMENT
The treatment goal for sickle cell retinopathy is to reduce the risk of, prevent or eliminate retinal neovascularization. Follow patients with asymptomatic sickle cell disease biannually with ocular examinations and dilated retinal evaluation. Since visual loss can result from both nonproliferative (subretinal neovascularization secondary to angioid streaks) and proliferative retinal disease, refer the patient to the retinologist when you see these retinal findings. Treat proliferative disease with fluorescein angiography and panretinal photocoagulation. Cryotherapy has not been proven to be efficacious and is associated with high complication rates.

CLINICAL PEARLS

Proliferative sickle cell retinopathy breaks down into five stages:
Stage 1: peripheral retinal arteriolar occlusions
Stage 2: peripheral arterio-venous anastamoses
Stage 3: neovascular fronds known as sea fans
Stage 4: vitreous hemorrhage as tractional forces and vitreous collapse tear fragile neovascular membranes
Stage 5: advanced disease, identified by severe vitreous traction and retinal detachment

Other causes of peripheral neovascularization include sarcoidosis, diabetes, retinal venous occlusion, Eales' disease, leukemia and ocular ischemic syndrome. However, the characteristic sea fan frond is diagnostic of sickle retinopathy.

For patients with suspicious findings, laboratory tests for sickle cell disease include the Sickledex, Sickle Prep and plasma hemoglobin electrophoresis.

Oral carbonic anhydrase inhibitors should be avoided. They may exacerbate the sickling of blood cells.