AUTHOR AND EDITOR INFORMATION

Section 1 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

INTRODUCTION

Section 2 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Background

This hereditary, genetically determined, hemolytic anemia occurs almost exclusively in blacks. Hemoglobin S (HbS) is formed by a single amino acid substitution, valine for glutamic acid in the sixth position from the N-terminal of the B-chain of the hemoglobin molecule.

Pathophysiology

Sickle cell disease refers to a group of conditions caused by HbS, the homozygous state (HbSS/sickle cell anemia) and the heterozygous states (sickle B thalassemia). Hemoglobin C (HbC) is formed by a single amino acid substitution of lysine for glutamic acid in the sixth position from the N-terminal of the B-chain of the hemoglobin molecule. Patients with HbAS have entirely normal growth, development, and exercise tolerance.

Frequency

United States

Sickle cell disease (HbS) is seen in 1-2% of blacks. Sickle cell trait (HbAS) is seen in 8-10% of blacks.

International

Same as above.

Mortality/Morbidity

• Patients with sickle cell disease experience crisis that presents with vascular occlusion, characterized by organ infarction and pain, acute hemolysis, sudden enlargement of the liver and spleen (caused by the trapping of erythrocytes), and sudden cessation of marrow function.
• The most common definable cause of crisis is infection, usually of the respiratory and urinary tracts.

Race

This condition almost exclusively affects blacks. See Frequency.

Sex

No gender preponderance exists.

Age

This condition may be undetected in younger persons.

CLINICAL

Section 3 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

History

Generally, the history includes pulmonary or respiratory infection and limb or abdominal pain with crisis and fever.

Physical

Limb and abdominal tenderness with enlargement of the liver or spleen

• The ocular manifestations of sickle cell disease result from vascular occlusion, which may occur in the conjunctiva, iris, retina, and choroid.
• The abnormalities of the posterior segment can be divided into 6 categories, as follows: Optic disc changes, posterior retinal and macular vascular occlusion, chronic macular changes, choroidal vascular occlusions, nonproliferative retinal changes, and proliferative retinal changes.
• Optic disc changes
• • Intravascular occlusions on the surface of the optic disc appears ophthalmoscopically as dark red intravascular spots.
  • These occlusions are transient and do not produce any clinical impairment. These changes are most common in hemoglobin SS disease but can occur in patients with hemoglobin SC and hemoglobin S.
• Posterior retinal and macular vascular occlusions
• • Retinal artery occlusions are either central or branch.
  • Peripapillary or macular arteriolar occlusions are rare. Retinal vein occlusions also are rare with sickle cell disease.
• Chronic macular changes (sickling maculopathy): Chronic macular vascular occlusions occur in sickle cell disease. These are manifested by microaneurysms resembling dots, hairpin-shaped vascular loops, and abnormal foveal avascular zone (FAZ).
• Choroidal vascular occlusions: Only 3 cases have been reported thus far in sickle cell disease.
• Nonproliferative retinal changes
• • Nonproliferative or background sickle retinopathy include venous tortuosity, salmon-patch hemorrhage, schisis cavity, and the black sunburst. Venous tortuosity probably is due to arteriovenous shunting from the retinal periphery. It can occur in many patients with hemoglobin SS and hemoglobin SC disease.
  • Salmon-patch hemorrhages are superficial intraretinal hemorrhages usually in the mid periphery of the retina adjacent to a retinal arteriole. The schisic cavity is a space caused by the disappearance of the intraretinal hemorrhage with iridescent spots and glistening refractive bodies in the schisis cavity.
  • The black sunburst consists of round chorioretinal scars usually located in the equatorial fundus. These lesions result from pigment accumulated around the vessels. They do not cause any visual symptoms.
• Proliferative sickle retinopathy
• • Proliferative sickle retinopathy (PSR) is the most severe ocular change in sickle cell disease. This is a peripheral retinal change most frequent in patients with hemoglobin SC but also can be present in hemoglobin S-thal disease, homozygous hemoglobin SS and hemoglobin AS and hemoglobin AC disease.
  • PSR is progressive and a major cause of visual morbidity in sickle cell disease. A desirable objective is to treat the neovascular tissue before a vitreous hemorrhage occurs.
  • Dr. Goldberg has classified PSR into the following 5 stages: peripheral arteriolar occlusions, arteriolar-venular anastomosis, neovascular proliferation, vitreous hemorrhage, and retinal detachment.
    • Stage I: The peripheral arteriolar vessels occlude with anteriorly located avascular vessels evident. Early in the process, the occluded arterioles are dark red lines but eventually turn into silver-wire–appearing vessels.
    • Stage II: Peripheral arteriolar-venular anastomosis occurs as the eye adjusts to peripheral arteriolar occlusion, blood is diverted from the occluded arterioles into the adjacent venules. Peripheral to these anastomoses no perfusion is present.
    • Stage III: At the junction of the vascular and avascular retina, the eye adapts with new vessel formation. These neovascular tufts resemble sea fans. Initially, the sea fans can be fed by a single arteriole and draining vessel. Later, as the sea fan grows in size, it is difficult to distinguish the major feeding and draining vessels. The sea fans may acquire a glial and fibrotic tissue envelope. This envelope may pull on the vitreous. A full-thickness retinal break, which may lead to total rhegmatogenous retinal detachment, may occur.
• Glaucoma secondary to rubeosis iridis may occur.

Causes

• Dehydration may precipitate a crisis in people with sickle cell disease (SS) or sickle cell trait (SC). Hydration (ie, drinking up to 1 qt of liquid qd) is helpful.
• Infection may cause a crisis. Preventing infections may avoid a sickle cell crisis.

DIFFERENTIALS

Section 4 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Other Problems to be Considered

Aortic arch syndrome
Carotid-cavernous fistula
Facioscapulohumeral muscular dystrophy
Incontinentia pigmenti
Familial exudative vitreoretinopathy
Hemoglobin C trait
Long-standing retinal detachment
Lupus erythematosus
Macroglobulinemia
Polycythemia vera
Talc and cornstarch emboli
Uveitis, including pars planitis

WORKUP

Section 5 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Lab Studies

• Complete blood count and sickle screen
• High index of suspicion of sickle cell disease with electrophoresis

Imaging Studies

• X-ray films to delineate subperiosteal hemorrhages of primarily long bones

TREATMENT

Section 6 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Medical Care

Treatment is directed toward the underlying infection, hypoxia, dehydration, and pain.

• Several systemic treatment strategies have evolved, including the inhibition of intracellular HbS polymerization and the polymer effects on the erythrocyte membrane, vasodilation, and modification of the interaction between the erythrocytes and blood vessels.
• • Because HbF (y-globin chains) inhibits the tendency of HbS erythrocytes to polymerize, increasing HbF levels by activating the gene for fetal hemoglobin may reduce the hemolytic and vascular occlusion complications of sickle cell disease.
  • This technique has been successful with the administration of 5-azacytidine, hydroxyurea, and, most recently, arginine butyrate.
• Medical ocular management may include topical medications; however, avoid carbonic anhydrase inhibitors, because they may cause further sickling and worsen the outflow obstruction. If the intraocular pressure remains elevated after a judicious trial of medical therapy, surgical intervention with an anterior chamber lavage is indicated.

Surgical Care

The goal of treatment is to eliminate existing neovascularization and, thus, eliminate the sequelae of PSR. Modalities to treat PSR include diathermy, cryotherapy, xenon arc photocoagulation, and argon laser photocoagulation.

Diathermy is used infrequently because of the high incidence of complications accompanying this procedure.

Cryotherapy, both single freeze-thaw and triple freeze-thaw, has been used to treat PSR. Triple-freeze thaw has a high complication rate. Single thaw is used to treat peripheral vitreous hemorrhage in the presence of vitreous hemorrhage.

Xenon arc and argon laser photocoagulation have been used to treat either the peripheral neovascularization or the feeder vessels to the neovascularization.

Ocular treatment is directed toward preventing vision loss from vitreous hemorrhage, retinal detachment, and epiretinal membranes.

• Photocoagulation applied through various techniques (eg, feeder vessel, focal scatter, peripheral circumferential scatter) is effective for treating proliferative sickle retinopathy and reducing the risk of vision loss.
• • Because of potential complications from photocoagulation and the tendency for regression, patients older than 40 years probably do not require treatment.
  • Complications of photocoagulation include choroidal neovascularization, retinal breaks, and peripheral choroidal ischemia.
• Surgical procedures include treatments for retinal detachments, nonclearing vitreous hemorrhage, and epiretinal membranes. Based on a 71% incidence of anterior segment ischemia in patients with PSR who are undergoing scleral buckling surgery, prophylactic preoperative exchange transfusions or erythropheresis is recommended.
• Risks associated with exchange transfusions and improvement in vitreoretinal surgical techniques warrant a careful reevaluation of prophylactic exchange transfusions.
• Perioperative measures to reduce the incidence of anterior segment ischemia include the following:
• • Nonsympathomimetic local anesthesia
  • Minimization of topical sympathomimetics
  • Supplemental oxygen for 48 hours after surgery
  • Avoiding wide encircling scleral buckling elements, expansile concentrations of intraocular gases, and carbonic anhydrase inhibitors
  • Closely monitoring and treating elevated intraocular pressure
• Anterior segment ischemia after surgery is an emergency. Although prognosis is notoriously poor, make all attempts to oxygenate the anterior segment. Options include hyperbaric oxygen therapy, continuous supplemental oxygen therapy, and transcorneal oxygen with goggles.
• Blood in the anterior chamber in patients with sickle cell disease is a medical emergency. A sickle screen is warranted for every black patient who has an unexplained hyphema. The environment of the anterior chamber promotes sickle hemoglobin polymerization, which can result in elevated intraocular pressure due to blockage of the trabecular meshwork.
• Because patients with sickle cell disease are particularly prone to central retinal artery occlusion and optic atrophy, even with mildly elevated intraocular pressures, closely monitor the intraocular pressure. Do not allow it to exceed 25 mm Hg for longer than 24 hours.

Consultations

• A physician who is familiar with sickle cell disease should follow the general condition.
• A retinal-trained ophthalmologist should follow for retinal disease.
• If secondary glaucoma is uncontrolled, a glaucoma-trained ophthalmologist may be necessary.

Activity

Vigorous physical activity may precipitate a sickle cell crisis.

MEDICATION

Section 7 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Treat infections promptly, if they occur. Pain can be relieved with oral or intramuscular medications. Folic acid and iron may help increase RBC production.

FOLLOW-UP

Section 8 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Further Outpatient Care

• Follow-up care depends on involvement with PSR; once stabilized, visits every 3-6 months may be adequate.
• When intraocular pressures are stabilized, the patient can be monitored every 6 months.

Deterrence/Prevention

• Prompt treatment of infections
• Regular use of medications
• At least 1 quart of fluid daily may avoid crisis.

Complications

• Bleeding may occur and limit physical activity.

Prognosis

• By controlling causes that precipitate a crisis, the prognosis is favorable.

Patient Education

• Patient and family education is vital to avoid a crisis.
• For excellent patient education resources, visit eMedicine's Blood and Lymphatic System Center. Also, see eMedicine's patient education article Sickle Cell Crisis.

MISCELLANEOUS

Section 9 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Medical/Legal Pitfalls

• Misdiagnosis of sickle cell disease and trait

REFERENCES

Section 10 of 10

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

• Babalola OE, Wambebe CO. When should children and young adults with sickle cell disease be referred for eye assessment?. Afr J Med Med Sci. Dec 2001;30(4):261-3. [Medline].
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• Hingorani M, Bentley CR, Jackson H, et al. Retinopathy in haemoglobin C trait. Eye. 1996;10 (Pt 3):338-42. [Medline].
• Jackson H, Bentley CR, Hingorani M, et al. Sickle retinopathy in patients with sickle trait. Eye. 1995;9 (Pt 5):589-93. [Medline].
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• Kehinde MO, Akinsola FB. Ocular findings in sickle cell disease patients in lagos. Niger Postgrad Med J. Sep 2004;11(3):203-6. [Medline].
• Leen JS, Ratnakaram R, Del Priore LV. Anterior segment ischemia after vitrectomy in sickle cell disease. Retina. Apr 2002;22(2):216-9. [Medline].
• Lima CS, Rocha EM, Silva NM. Risk factors for conjunctival and retinal vessel alterations in sickle cell disease. Acta Ophthalmol Scand. Apr 2006;84(2):234-41. [Medline].
• Nasrullah A, Kerr NC. Sickle cell trait as a risk factor for secondary hemorrhage in children with traumatic hyphema. Am J Ophthalmol. 1997;123:783-790P. [Medline].
• Penman AD, Talbot JF, Chuang EL, et al. New classification of peripheral retinal vascular changes in sickle cell disease. Br J Ophthalmol. Sep 1994;78(9):681-9. [Medline].
• Shakoor A, Blair NP, Shahidi M. Imaging retinal depression sign in sickle cell anemia using optical coherence tomography and the retinal thickness analyzer. Arch Ophthalmol. Sep 2005;123(9):1278-9. [Medline].
• Traore J, Boitre JP, Bogoreh IA, et al. Sickle cell disease and retinal damage: a study of 38 cases at the African Tropical Ophthalmology Institute (IOTA) in Bamako. Med Trop (Mars). Jun 2006;66(3):252-4. [Medline].
• Wisotsky BJ, Tesser PM, Schultz JS. Trabecular meshwork hemorrhage in a patient with sickle cell trait. Arch Ophthalmol. 1995;113:381-382. [Medline].

Article Last Updated: Oct 12, 2006