Hospital for Sick Children's, The: Atlas of Pediatric Ophthalmology & Strabismus, 1st Edition

Ocular Manifestations of Systemic Disease



Alex V. Levin

Thomas W. Wilson

David Smith

Abnormalities in the hematologic system will often have associated ocular diseases or findings. All four major components of the blood (serum, red blood cells, white blood cells, and coagulation factors) have been implicated as the underlying cause of vision loss and eye disease. The maintenance of ocular health depends upon the hematologic system.

Anemia and abnormalities of red blood cell function and morphology will lead to mild to severe ischemia within the eye. Mild ischemia will be manifested as cotton wool spots (ischemia of the nerve fiber layer), microaneurysms, and scattered hemorrhages throughout the retina. Severe ischemia will lead to neovascular proliferation and the potential for significant vision loss from extensive hemorrhage or tractional retinal detachment.

Proliferation of the white blood cells in lymphoma and leukemia will have direct (invasion in ocular tissues) and indirect (increased risk of infection due to immunosuppression) effects on the visual system. White blood cell abnormalities have been reported in the ataxia telangiectasia (telangiectatic conjunctival vessels, progressive ataxia, decreased IgA, and decreased T-cell–mediated immunity) and Chediak-Higashi (albinism and defective chemotaxis and degranulation of neutrophils) syndromes.

Abnormalities of coagulation will often have associated conjunctival and retinal hemorrhages. The retinal hemorrhages of coagulopathies are typically few in number and located in the posterior pole. Disorders of blood serum including hyperviscosity can cause retinal venous disease.



Figure 18.1 Sickle Cell Anemia— Peripheral Retinal Vasculopathy

Sickle cell anemia is a disease characterized by chronic hemolysis secondary to abnormal red blood cells. During deoxygenation, the sickle hemoglobin changes its configuration to form a filamentous structure that leaves the red blood cell rigid. There is an abnormal valine substitution in the sixth position of the β chain. Clinical manifestations include acute painful crises secondary to vaso-occlusion. More severe crises can cause significant ischemic damage to the heart, liver, and kidneys. This photograph illustrates peripheral abnormal vasculature.


Figure 18.2 Sickle Cell Anemia— Neovascularization

Sickle cell disease can lead to neovascularization of the disc, macula, and peripheral retina. Proliferation of new blood vessels in the peripheral retina is the most common location. Proliferative sickle retinopathy is classified into five stages: (a) peripheral arterial occlusion; (b) peripheral arteriolar–venular anastomoses; (c) neovascular proliferation; (d) vitreous hemorrhage; and (e) retinal detachment. In the third stage, the proliferation of new blood vessels in the periphery typically forms a C-fan configuration as seen here. Treatment of proliferative disease includes cryotherapy and laser photocoagulation.


Figure 18.3 Sickle Cell Anemia— Salmon Patch

A salmon patch is a retinal hemorrhage located in the subhyaloid space or superficial retina. It is typically located in the midperiphery and becomes an orange-red color over several days. After the hemorrhage is absorbed, there may be a schisis cavity containing refractile bodies known as iridescent spots. These iridescent spots are actually macrophages filled with iron from the degrading hemoglobin.




Figure 18.4 Sickle Cell Anemia— Sunburst

This photograph demonstrates the classic black sunburst seen in sickle cell retinopathy. The lesions are round or oval and can be as large as two disc diameters. They are dark, black, and located in the peripheral retina. They represent retinal pigment epithelium that has migrated through the Bruch membrane during a vaso-occlusive episode within the retina. Following the migration, the retinal pigment epithelium undergoes hyperplasia.


Figure 18.5 Sickle Cell Disease— Orbital Bone Infarction

One of the cardinal clinical manifestations of sickle cell disease are the recurrent bony vaso-occlusive crises characterized chiefly by pain, often with overlying edema. Rarely, the orbital bones may be involved, resulting in painful periorbital and/or orbital swelling that may mimic periorbital or orbital cellulitis (Chapter 11: Orbit, Figs. 11.8 and 11.9). Proptosis may also be observed. However, in sickle cell disease the optic nerve is almost always spared and patients are rarely febrile.


Figure 18.6 Thalassemia

Thalassemia is a group of hypochromic anemias secondary to abnormal production of globin chains. The two types of globin chains—α chain and β chain—are deficient in α-thalassemia and β-thalassemia. One of the two globin chains is deficient in thalassemia minor, and both chains are absent in thalassemia major. Both α- and β-thalassemia lead to microcytic anemias, and the level of ocular disease is proportional to the severity of the anemia. Ischemia of the retina and optic nerve can lead to chronic optic neuropathy and retinal cotton wool spots. Subretinal, intraretinal, and preretinal hemorrhages are also associated with chronic anemia.




Figure 18.7 Leukemia—Retinal Hemorrhage

Ocular manifestations can occur in both myelogenous and lymphocytic leukemia and are more common in the acute leukemias. Leukemia can cause abnormalities of the retina, choroid, optic nerve, and anterior segment. Retinal manifestations include cotton wool spots, retinal hemorrhages, venous stasis disease, and leukemic retinal infiltrates. Retinal hemorrhages can occur preretinally (boat-shaped hemorrhages or well-circumscribed round hemorrhages), intraretinally (dot-blot hemorrhages), or subretinally (dark, well-circumscribed hemorrhages). Hemorrhages may have a white center due to leukemic infiltrates, fibrin, or ischemia.


Figure 18.8 Leukemia—Retinopathy

Hyperviscosity due to the increased number of white blood cells in the serum causes microinfarcts within the nerve fiber layer and presents clinically as cotton wool spots. Other white lesions represent leukemic retinal infiltrates. These infiltrates cluster at smaller vessels, in particular in the far periphery where larger infiltrative masses may be found. Infiltrates are almost always accompanied by retinal hemorrhage.


Figure 18.9 Leukemia—Choroidal Invasion

Choroidal involvement is a common ocular manifestation of leukemia. Histopathologic examination of the choroid will often reveal choroidal involvement that was not detected on fundus examination. Thickening of the choroid on B-scan ultrasound may be the only indicator. Leukemic infiltrates of the choroid can change the permeability of the retinal pigment epithelium and cause serous retinal detachment, as shown here.




Figure 18.10 Leukemia—Optic Nerve Infiltration

In central nervous system leukemia, the optic nerve may become involved and when involved indicates a poor prognosis. Optic nerve infiltration leads to compression of the optic nerve and significant permanent visual loss. Optic nerve pallor and edema are clinical signs of optic nerve involvement. Serial examinations should be performed to assess the optic nerve function. Visual acuity, color vision, visual field, and pupillary examination are required with each visit. Progressive vision loss is an indication for aggressive treatment, including intrathecal chemotherapy and optic nerve radiation. Despite these therapies, progressive visual loss is common.


Figure 18.11 Leukemia—Anterior Chamber

Involvement of the anterior segment is an uncommon manifestation of systemic leukemia; however, patients can present with diffuse infiltration of the iris. This can lead to iritis and hypopyon. Patients may also develop glaucoma secondary to direct infiltration of the trabecular meshwork or to debris obstructing the trabecular meshwork. Patients may present with heterochromia or hypopyon. A paracentesis should be considered in cases where the cause of the pseudohypopyon is not clear. Any patient with known leukemia and iritis should have a paracentesis and iris biopsy before steroid treatment.


Figure 18.12 Leukemia— Spontaneous Ecchymosis

This photograph illustrates the coagulopathy often associated with leukemia due to infiltration of the bone marrow. This child may have been diagnosed incorrectly to have cellulitis or to have been abused. Orbital hemorrhage or leukemic infiltrate may also occur and present as acute proptosis.




Figure 18.13 Anemia

Chronic anemia can be caused by increased red blood cell loss or decreased red cell production. Causes of decreased production include iron deficiency, folic acid deficiency, lead poisoning, bone marrow abnormalities, and thalassemia. Increased red blood cell loss can be secondary to autoimmune diseases and hemoglobinopathies. Ocular manifestations of anemia include ischemia of the nerve fiber layer causing cotton wool spots, shown here. Retinal hemorrhages occur only in severe anemia, especially when thrombocytopenia is also present. Usually they are few in number, intraretinal or preretinal, and confined to the posterior pole. Chronic anemia and deficiencies of vitamin B12 and folic acid, which cause anemia, can lead to irreversible optic neuropathy.


Figure 18.14 Histiocytosis

Histiocytosis is a group of disorders that include Hand-Schüller-Christian disease, eosinophilic granuloma, and Letterer-Siwe syndrome. These disorders have in common an antigen-processing disorder of Langerhans cells. Patients with histiocytosis will often have skeletal involvement, with the skull and face being most commonly affected. Patients may present with localized edema and pain. Lymphadenopathy and hepatosplenomegaly are common.




Figure 18.15 Histiocytosis

Histiocytosis may involve the orbit, as demonstrated in this computed tomography scan. It is typically bilateral and leads to exophthalmia. Other involved organs include the lungs, the pituitary gland, and the liver. Biopsy shows Langerhans cells with Birbeck granules. Immunosuppressive therapy including prednisone, methotrexate, and cyclophosphamide has been shown to slow the progression of the disease.


Figure 18.16 Thrombocytopenia

Clinically evident bleeding from thrombocytopenia is uncommon with levels above 30,000 platelets. When bleeding does occur, common manifestations include petechia, subconjunctival hemorrhage, epistaxis, or gum bleeding. Less commonly, and with more severe depression of the platelet levels, retinal hemorrhages, shown here, may occur. These tend to be intraretinal or preretinal, small in size and number, and confined to the posterior pole.