Ophthalmologic Manifestations of Sickle Cell Disease

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Ophthalmologic Manifestations of Sickle Cell Disease

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The ocular manifestations of sickle cell disease (SCD) result from vascular occlusion, which may occur in the conjunctiva, iris, retina, and choroid. Because the ocular changes produced by SCD can be seen in other diseases, it is important to rule out other causes of occlusion, including central retinal vein occlusion, Eales disease, and retinopathy secondary to diabetes and other disorders. [1] Other causes of ocular changes that should also be considered include familial exudative vitreoretinopathy, polycythemia vera, talc and cornstarch emboli, and uveitis.

Treatment is directed toward preventing vision loss from vitreous hemorrhage, retinal detachment, and epiretinal membranes. [2, 3] Treatment may be medical or surgical.

Go to Sickle Cell Anemia for complete information on this topic.

The abnormalities of the posterior segment can be divided into 6 categories, as follows [4, 5, 6, 7] :

Optic disc changes

Posterior retinal and macular vascular occlusion

Chronic macular changes (sickling maculopathy)

Choroidal vascular occlusions

Nonproliferative retinal changes

Proliferative retinal changes

Intravascular occlusions on the surface of the optic disc appear ophthalmoscopically as dark-red intravascular spots. These occlusions are transient and do not produce any clinical impairment. [8] These changes are most common in hemoglobin SS disease but can also occur in patients with hemoglobin SC and hemoglobin S.

Retinal artery occlusions are either central or branch. Peripapillary or macular arteriolar occlusions are rare. Retinal vein occlusions also are rare with SCD.

Chronic macular vascular occlusions occur in SCD. These are manifested by microaneurysms resembling dots, hairpin-shaped vascular loops, and abnormal foveal avascular zone (FAZ).

This is an extremely rare manifestation of SCD. Only 3 cases have been reported thus far in the literature.

Nonproliferative or background sickle retinopathy includes the following manifestations:

Venous tortuosity

Salmon-patch hemorrhage

Schisis cavity

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. They are usually seen in the mid periphery of the retina adjacent to a retinal arteriole.

The schisis cavity is a space caused by the disappearance of the intraretinal hemorrhage. Nonproliferative sickle retinopathy features 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 (PSR) is the most severe ocular change in SCD. This is a peripheral retinal change most frequent in patients with hemoglobin SC but also can be present in patients with hemoglobin S-thalassemia disease, homozygous hemoglobin SS, and hemoglobin AS and hemoglobin AC disease. [9, 10]

PSR is progressive. A desirable objective is to treat the neovascular tissue before a vitreous hemorrhage occurs.

Goldberg classified PSR into the following 5 stages:

Peripheral arteriolar occlusions

Arteriolar-venular anastomosis

Neovascular proliferation

Vitreous hemorrhage

Retinal detachment

In 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 they turn into silver-wire–appearing vessels.

In stage II, peripheral arteriolar-venular anastomosis occurs as the eye adjusts to peripheral arteriolar occlusion, and blood is diverted from the occluded arterioles into the adjacent venules. Peripheral to these anastomoses, no perfusion is present.

In stage III, new vessel formation occurs at the junction of the vascular and avascular retina. 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.

Sickle cell vasoocclusive events can affect every vascular bed in the eye, often with visually devastating consequences in advanced stages of the disease.

Anterior segment abnormalities include the following:

Segmentation “corkscrew” conjunctival vessel, more commonly seen in the inferior bulbar conjunctiva

Iris infarct and atrophy

Cataracts

Phthisis bulbi

Hyphema

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

The goal of treatment is to eliminate existing neovascularization and, thus, to eliminate the sequelae of proliferative sickle retinopathy (PSR). Modalities to treat proliferative sickle retinopathy 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 freeze-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.

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 may be performed to treat 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 the 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. [11]

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. [12, 13] 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.

Jackson H, Bentley CR, Hingorani M, Atkinson P, Aclimandos WA, Thompson GM. Sickle retinopathy in patients with sickle trait. Eye (Lond). 1995. 9 ( Pt 5):589-93. [Medline].

Ganesh A, Al-Zuhaibi S, Pathare A, William R, Al-Senawi R, Al-Mujaini A. Orbital infarction in sickle cell disease. Am J Ophthalmol. 2008 Oct. 146(4):595-601. [Medline].

Lima CS, Rocha EM, Silva NM, Sonatti MF, Costa FF, Saad ST. Risk factors for conjunctival and retinal vessel alterations in sickle cell disease. Acta Ophthalmol Scand. 2006 Apr. 84(2):234-41. [Medline].

Akinsola FB, Kehinde MO. Ocular findings in sickle cell disease patients in Lagos. Niger Postgrad Med J. 2004 Sep. 11(3):203-6. [Medline].

Hingorani M, Bentley CR, Jackson H, Betancourt F, Arya R, Aclimandos WA. Retinopathy in haemoglobin C trait. Eye (Lond). 1996. 10 ( Pt 3):338-42. [Medline].

Sokol JA, Baron E, Lantos G, Kazim M. Orbital compression syndrome in sickle cell disease. Ophthal Plast Reconstr Surg. 2008 May-Jun. 24(3):181-4. [Medline].

Wisotsky BJ, Tesser PM, Schultz JS. Trabecular meshwork hemorrhage in a patient with sickle cell trait. Arch Ophthalmol. 1995 Mar. 113(3):381. [Medline].

Goldbaum MH, Jampol LM, Goldberg MF. The disc sign in sickling hemoglobinopathies. Arch Ophthalmol. 1978 Sep. 96(9):1597-600. [Medline].

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.

Gill HS, Lam WC. A screening strategy for the detection of sickle cell retinopathy in pediatric patients. Can J Ophthalmol. 2008 Apr. 43(2):188-91. [Medline].

Leen JS, Ratnakaram R, Del Priore LV, Bhagat N, Zarbin MA. Anterior segment ischemia after vitrectomy in sickle cell disease. Retina. Apr 2002. 22(2):216-9.

Karim A, Laghmari M, Dahreddine M, Guedira K, Ibrahimy W, Essakali N. [Hyphema with secondary hemorrhage: think about sickle cell disease]. J Fr Ophtalmol. 2004 Apr. 27(4):397-400. [Medline].

Nasrullah A, Kerr NC. Sickle cell trait as a risk factor for secondary hemorrhage in children with traumatic hyphema. Am J Ophthalmol. 1997 Jun. 123(6):783-90. [Medline].

Mark Ventocilla, OD, FAAO Adjunct Clinical Professor, Michigan College of Optometry; Editor, American Optometric Association Ocular Surface Society Newsletter; Chief Executive Officer, Elder Eye Care Group, PLC; Chief Executive Officer, Mark Ventocilla, OD, Inc; President, California Eye Wear, Oakwood Optical

Mark Ventocilla, OD, FAAO is a member of the following medical societies: American Academy of Optometry, American Optometric Association

Disclosure: Nothing to disclose.

Hampton Roy, Sr, MD Associate Clinical Professor, Department of Ophthalmology, University of Arkansas for Medical Sciences

Hampton Roy, Sr, MD is a member of the following medical societies: American Academy of Ophthalmology, American College of Surgeons, Pan-American Association of Ophthalmology

Disclosure: Nothing to disclose.

Hampton Roy, Sr, MD Associate Clinical Professor, Department of Ophthalmology, University of Arkansas for Medical Sciences

Hampton Roy, Sr, MD is a member of the following medical societies: American Academy of Ophthalmology, American College of Surgeons, Pan-American Association of Ophthalmology

Disclosure: Nothing to disclose.

Steve Charles, MD Director of Charles Retina Institute; Clinical Professor, Department of Ophthalmology, University of Tennessee College of Medicine; Adjunct Professor of Ophthalmology, Columbia College of Physicians and Surgeons; Clinical Professor Ophthalmology, Chinese University of Hong Kong

Steve Charles, MD is a member of the following medical societies: American Academy of Ophthalmology, American Society of Retina Specialists, Club Jules Gonin, Macula Society, and Retina Society

Disclosure: Alcon Laboratories Consulting fee Consulting; OptiMedica Ownership interest Other; Topcon Medical Lasers Consulting fee Consulting

Russell P Jayne, MD Consulting Vitreoretinal Surgeon, The Retina Center at Las Vegas

Russell P Jayne, MD is a member of the following medical societies: American Medical Association, American Society of Cataract and Refractive Surgery, and American Society of Retina Specialists

Disclosure: Nothing to disclose.

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Medscape Reference Salary Employment

Ophthalmologic Manifestations of Sickle Cell Disease

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