Ординатура / Офтальмология / Английские материалы / Clinical Medicine in Optometric Practice_Muchnick_2007

318 THE EYE IN SYSTEMIC DISEASE

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Whitcup SM:Anterior uveitis. In Nussenblatt RB,Whitcup SM, eds:

Uveitis: fundamentals and clinical practice, Philadelphia, 2004, Mosby.

When systemic disease affects the posterior segment of the eye, the results can be devastating.

Retinal and choroidal scarring can cause permanent visual acuity and visual field loss. Infections, systemic disease, and toxic reactions can cause such extensive histopathological changes that the vision of our patients is inexorably and forever challenged.

Often the first indication of a systemic disease is a posterior segment manifestation detected by funduscopy. All posterior segment lesions should be evaluated for possible systemic disease implications. This chapter details the most significant of the systemic diseases to manifest lesions within the retina and choroids. Included are discussions concerning infections, toxic reactions,

hypertensive retinopathy, carotid artery disease, connective tissue diseases, and hematological disorders.

HYPERTENSIVE RETINOPATHY Systemic Hypertension

Systemic hypertension is classified as a minimum diastolic blood pressure of 85 mm Hg or a minimum systolic blood pressure of 140 mm Hg in a patient older than 50 years. More than 90% of cases of hypertension are idiopathic in nature, with the remainder caused by congenital or acquired renal disease.

Systemic hypertension increases the risk of coronary artery, cerebrovascular, peripheral, vascular, and

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renal disease. The impact of such vascular pathologies is reflected in the prevalence of renal failure, strokes, and heart attacks associated with chronic, untreated high blood pressure.

Effects of Systemic Hypertension

on Retinal and Choroidal Vasculature

Hypertension induces retinal vascular constriction and eventual sclerosis that can be visualized directly by ophthalmoscopy. Changes in the choroidal vasculature, deep to the retina, cause disturbances in the overlying retinal pigmentary epithelium that can be ophthalmoscopically evaluated. Because hypertensive changes in the vasculature of the posterior segment reflect the effects of chronic high blood pressure and the adequacy and severity of hypertensive control, funduscopic findings may help guide the therapeutic strategy. In particular, the effects of chronic, untreated high blood pressure on the kidneys, central nervous system (CNS), cardiovascular system, and hemopoietic system can be indirectly implied by direct observation of hypertensive changes within the retinal and choroidal blood vessels.

The tissue of the retina reacts to vascular sclerosis in the same way as the tissue of the CNS and cardiovascular system; edema, ischemia, and infarction characterize the resultant vascular ischemia. In a similar way, hypertension causes renal vascular changes that are reflected in the retinal circulation.

Hypertension affects retinal circulation differently than choroidal circulation, because the retinal blood vessels are similar to the blood vessels of the CNS, with a strong blood-retinal barrier maintained by tight cell junctions. Choroidal blood vessels lack these tight junctions, however, and thus an insufficient or nonexistent blood-choroidal barrier is present. Another difference is evidenced by the differences between the retinal and choroidal blood vessels responses to changes in blood pressure, ocular pressure, and blood oxygenation. Retinal blood vessels are characterized by autoregulation in response to these influences, and the choroidal vascular tone is under sympathetic nervous system control. Because of these differences, systemic hypertension will affect the retinal blood vessels differently than the choroidal blood vessels, although the retinal vasculature is most often evaluated because it is easiest to visualize.

It is important to note that the classification of hypertensive retinopathy used to be of prognostic value in helping to determine the effect of systemic hypertension on survival rate. Recent advances in the medical mitigation of hypertension has meant a decreasing role for the classification of hypertensive retinopathy, however, and it is of most value now in determining the effect of hypertension on the circulation of the brain, heart, and kidneys.

Systemic hypertension most commonly affects the small, muscular arteries of the retina, sometimes referred to as retinal “arterioles,” but this term may be a histiological misnomer. The space around these retinal arteries, the perivascular space, is small in the young person, and thus the image of the artery is that of a sleek, red tube. With age, however, the perivascular space accumulates smooth muscle cells and glial cells from the basement membrane, and thus an increase in the size of the light reflex occurs. This process of vascular sclerosis is sped up by systemic hypertension.

Although the retinal arteries possess a blood-retina barrier, this may be breached in several disease states, including hypertension. When this breach occurs, a hemorrhage, or leakage of blood, occurs from the site of the break. When this is caused by hypertension, the exudative retinopathy affects the shallow capillaries or arterioles, and the blood spreads out along the nerve fiber layer, taking on the appearance of a flame-shaped hemorrhage.

The Four Phases of Hypertensive Retinopathy

Four phases of hypertensive retinopathy exist, but these phases may not occur sequentially and any phase may occur in isolation. As such, these are not so much stages of hypertensive retinopathy as they are phases.

The Vasoconstrictive Phase

In hypertensive retinopathy, the vasoconstrictive phase is characterized by asymptomatic diffuse and focal constrictions of the precapillary retinal arterioles. This phase is best appreciated using slit-lamp biomicroscopy with red-free illumination. Vasoconstriction is best seen after the second branching of a retinal artery. The vasoconstrictive phase is typically an early, reversible, and treatable stage of hypertension. Blood pressure readings should be taken in the office when the vasoconstrictive phase is discovered, and the patient referred to the family physician for a systemic evaluation.

The Sclerotic Phase

More advanced hypertensive retinopathy results in the sclerotic phase, which rarely develops if the patient with vasoconstriction of the arterioles is promptly treated. These more sclerotic vessels are characterized by a narrowing of their caliber along with a widening of the light reflex, vascular tortuosity, an increase in their angle of branching, and arteriole nicking.

Unfortunately, arteriole narrowing is difficult to quantify, and a comparison of the size of the artery to the vein is not appropriate because the veins may be dilated. Arteriole narrowing may be mild, moderate, or severe.

Arteriovenous crossing changes can occur in the environment of hypertensive retinopathy. These changes have been related to left ventricular hypertrophy. One such change is “nicking,” in which a vein underlying an artery is deflected in its course. Mild (slight venous deflection), moderate (venous tapering, constriction or deflection), or severe (impending venous occlusion with hemorrhage and exudates distal to the crossing) nicking may be present. Dilation of the retinal vein distal to the arteriovenous crossing is known as banking, because the blood distal to the crossing is saved like “money in the bank,” not because the vein banks, or is deflected, in its course.

Sclerosis of the arterial wall can also develop in the sclerotic phase. This condition produces a widened light reflex compared with the width of the light reflex in the patient without systemic hypertension. Mild sclerosis (mildly increased light reflex), copper wiring, or silver wiring may be present. The copper color is produced by sclerosis that covers the entire anterior surface of the retinal artery. The silver color of advanced sclerosis is produced by thickening and hyalinization of the vessel wall such that the artery looks like a silver cord, although active blood flow may still be present.

With chronic hypertension, an increase in the tortuosity of the retinal arterioles may be present. This must be differentiated from congenital tortuosity, which is a benign condition.

Prolonged hypertension may also produce an increase in the angle of arterial branching, with greater blood pressure producing a larger angle. This angle is best visualized between the second and third arteriole bifurcation. It may be mild (45 degrees to 60 degrees), moderate (60 degrees to 90 degrees), or severe (more than 90 degrees).

The Exudative Phase

The third phase of hypertensive retinopathy is the exudative phase, which is usually accompanied by the vasoconstrictive phase, the sclerotic phase, or both. In the exudative phase, a disruption of the blood-retinal barrier occurs as measured by fluorescein angiography, and a leakage of fluid and blood cells from the circulatory system is present. This results from the inability of the autoregulatory system of the arteriole wall to overcome the perfusion pressure within the arteriole lumen. A consequential breach of the vessel wall occurs with leakage and a disruption of blood flow that results in retinal tissue ischemia. The earliest signs of the exudative phase are flame-shaped hemorrhages that result from leakage of superficial arterioles with spreading of the blood along the nerve fiber layer. If the hemorrhage breaks through the internal limiting membrane, a boat-shaped hemorrhage forms within the subhyaloid space in the posterior pole.

If plasma lipoproteins, triglycerides, and cholesterol leak from the arteriole, then hard, waxy exudates may form. These exudates are bright yellow, form in the posterior pole, and may assume a star-shaped appearance around the macula. This appearance results from the exudates leaking along the nerve fiber layer in a linear fashion, radiating away from the fovea.

Exudation can disrupt blood circulation to such a degree that the resulting lack of oxygenation to the retinal tissues results in ischemia. The whitish-gray or yellow patches of infarcted retinal tissue are known as cotton-wool spots (CWS). CWS most often are produced at right angles to the nerve fiber layer and are superficial to the blood vessels. CWS represent ischemic retinal tissue, as evidenced by fluorescein angiography that will frequently reveal nonperfusion in these areas. Ischemic retinal tissue may produce collaterals to distribute blood flow around the CWS, and the presence of these new blood vessels help to confirm the presence of CWS.

Complications of Sclerosis Phase

The fourth and final stage of hypertensive retinopathy occurs when complications occur because of the sclerotic phase. These complications include vascular occlusions, microaneurysms, and epiretinal membrane formation. In addition, retinal ischemia may lead to neovascularization, vitreous hemorrhage, retinal detachment, and cystoid macular edema. The earliest symptom of these changes is usually a reduction in visual acuity, which normally is unaffected by hypertensive retinopathy because the changes are scattered and peripheral to the macula. In the fourth phase of this retinopathy, however, maculopathy secondary to edema, exudation, or membrane formation can lead to blurred vision.

Malignant hypertension may be considered an end result of the fourth stage of hypertensive retinopathy, wherein the systemic hypertension has produced swelling of the optic nerve head. In his classification scheme, Scheie defined stage four hypertensive retinopathy as the presence of papilledema. Bilateral disc edema, known as papilledema, appears as a disc with blurry margins, a filling of the optic cup, and congested retinal veins. This congestion is the result of an accumulation of axoplasmic debris in the lamina of the optic nerve head, which results in swelling of the axons and leads to disc edema.

Effect of Systemic Treatment on Hypertensive Retinopathy

With treatment of the systemic hypertensive condition, the associated retinopathy may become stabilized or even reversed in some instances. Systemic medical or surgical intervention may reduce the risk of retinal

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complications in the sclerotic phase including vascular occlusion and macular involvement. Typically, 6 to 12 months after systemic hypertension control the retinal hemorrhages, exudates, and CWS resolve. Malignant hypertension requires emergency control of the systemic hypertensive condition, and the papilledema usually resolves within weeks.

CAROTID ARTERY DISEASE The Carotid-Eye Axis

Two major oculovisual ramifications of carotid disease exist. The first occurs when atherosclerosis of the carotid artery causes the formation of emboli that travel either to the eye or brain. On entering the retinal vascular system, the emboli may become lodged in an arterial bifurcation, ultimately yielding a loss of vision caused by arterial occlusion. A carotid artery emboli that leads to the brain may cause symptoms of a transient ischemic attack (TIA), including a variety of visual field defects. A vascular specialist must evaluate the carotid arteries whenever emboli are visualized in the retinal vascular arterial tree.

The second affect of the carotid artery on the eye may occur because of complete stenosis of the vessel that results in ocular ischemic syndrome (OIS). OIS is also known as venous stasis retinopathy.

Retinal Arterial Emboli

Etiology

An embolism represents the presence of a material foreign to the involved blood vessel. In the eye, the most common source of an embolism is from the carotid artery, and the material involved is usually cholesterol, calcium, or fibrin. The embolism most often lodges in a retinal artery that is narrower than the plug of material, or at a bifurcation of an artery. The embolism may be visualized as a brilliant and small white, yellow, or gray pinpoint of light shining from the lumen of a retinal artery. Typically, some blood flow occurs around the obstruction, thus blood may be seen on both sides of the embolus within the lumen of the vessels. Usually, a white embolus represents a plug composed mostly of calcium, a yellow plug is primarily cholesterol, and a gray plug is composed of mostly fibrin. The origin of the plug is typically a thrombus that broke off from the wall of the carotid artery. In all cases of retinal embolism, a coronary source of the material should also be considered, particularly if the plaque is white and therefore composed mostly of calcium.

Symptoms and Signs

The retinal arterial embolism, often termed a Hollenhorst plaque, may cause no symptoms and is often discovered on a routine eye examination. If a

symptom occurs associated with the plaque, it is usually a fleeting loss of vision that lasts from seconds to hours. The appearance of multiple emboli over time within the arterial tree produces fleeting losses of vision for seconds at a time. The losses of vision occur because a temporary occlusion of an artery occurs, followed by a breaking up of the embolism, the components of which are taken downstream into the finer capillary system. A larger embolism can become lodged in a vessel permanently and cause massive ischemia to part of the retina, with a concurrent permanent loss of vision or of the visual field. Alternatively, in some cases a large embolism lodges in a vessel and yet produces no symptomology at all. This situation is usually the result of blood flow coursing around the embolus and continuing to supply the retinal tissue.

Systemic Evaluation

The symptomology of the visual TIA, or the discovery of a Hollenhorst plaque on ophthalmoscopy, should instigate a dedicated search for the etiology of the embolism. The optometrist should draw or photograph the embolism for documentation purposes. Next, auscultation of both carotid arteries should be undertaken to search for a thrombus that produces a bruit. The bruit is a “whooshing” sound heard between the quick beats of the heart and represents irregular blood flow around a thrombus. On pinpointing a bruit in a carotid artery, the optometrist should draw in indelible ink a circle around the side on the neck of the patient. This will locate the bruit for the family physician and is necessary, because the bruit is easy to miss. The patient should be referred to his or her family doctor within 48 to 72 hours with a photo or drawing of the retinal plaque, and an indication on the neck of the patient where the bruit was auscultated. The patient should be referred to his or her physician even if the carotid artery sounded normal, because a bruit will only occur if between 50% and 85% occlusion of the vessel is present.

Referral for Vascular Evaluation

The finding of a retinal embolism or a bruit should provide motivation for a vascular work-up. The vascular specialist will look for evidence of carotid or coronary thrombus formation. Discovery of arterial disease may prompt medical or surgical intervention.

Treatment

Left untreated, the patient with retinal arterial plaques is at extreme risk for stroke, retinal vascular occlusive disease, myocardial infarction, and kidney failure. The use of so-called “blood thinning” agents, such as aspirin, Coumadin, or heparin, may be as effective as surgical intervention at preventing target organ damage. Carotid endarterectomy is a surgical approach in which the thrombus formation of the artery is removed, thus

reducing the risk of embolism formation. Significant risks accompany this surgical approach, however, and a medical approach can be just as effective at reducing the risk of ultimate target organ damage or death of the patient.

Ocular Ischemic Syndrome

Demographics

Ocular ischemic syndrome, or OIS, has been known in the past as venous stasis retinopathy. OIS usually affects people from ages 50 to 90 years, and the mean age of involvement is 65 years. Males are affected twice as often as females and race does not appear to be a risk factor. The condition is unilateral in 80% of cases.

Symptomology

Of individuals with OIS, 90% noted a loss of vision that typically motivated them to seek out an eye examination. The decrease in vision is typically gradual and prolonged during a period of several months. An abrupt loss of vision occurs in 10% of cases, and is usually caused by a central retinal artery occlusion (CRAO) secondary to OIS. In these cases ophthalmoscopy will demonstrate a cherry red spot of the retina, and the occlusion will be the result of neovascular glaucoma causing an intraocular pressure that exceeds the perfusion pressure of the central retinal artery. Nearly half of all OIS patients complain of a dull eye ache on the involved side.

Clinical Signs

Visual acuity is reduced from 20/25 to 20/40 in a third of cases. In approximately one third of cases, visual acuity drops between 20/50 and 20/400. The remaining third of OIS patients have a dramatic reduction of VA from 20/800 to no light perception. Slit-lamp evaluation reveals flare in the anterior chamber of OIS eyes with possible rubeosis iridis. Occasional keratic precipitates may be found on the corneal endothelium. Cells may be demonstrated in the anterior chamber. Thus, any uveitis of unknown etiology in a patient 50 years or older should be evaluated for OIS. Neovascularization of the iris is seen in approximately 60% of eyes with OIS. Therefore, any rubeosis iridis in a patient 50 years or older with no history of diabetes or retinal vein occlusion should prompt a search for OIS. In the posterior pole, OIS can cause midperipheral dot and blot hemorrhages. These hemorrhages are found in 80% of eyes affected with OIS. The retinal arterial system may demonstrate microaneurysms, and approximately 30% of eyes affected with OIS have neovascularization of the optic nerve head. Central retinal artery obstruction (with the production of a cherry-red spot) with concomitant neovascularization of the iris should prompt a suspicion of OIS.

Cause of OIS

Occlusion of the carotid artery of 90% or more is necessary to cause OIS on the ipsilateral side. This reduction of homodynamic pressure within the central retinal artery reduces blood flow to ocular tissues and yields ischemia, infarction, and neovascularization.

Systemic Associations

Approximately half of all patients with OIS have been diagnosed with systemic hypertension. In addition, approximately half have been diagnosed with diabetes and approximately one third have coronary artery disease. Approximately one quarter of all patients who develop OIS have a history of cerebral stroke, and approximately 4% of OIS patients have a cerebrovascular accident (CVA) each year. Nearly 50% of patients who develop OIS die within 5 years, usually from stroke, cancer, or heart disease.

Treatment

Prompt referral for treatment is necessary, because central retinal artery occlusion has been observed after the diagnosis of OIS. Carotid endarterectomy has been shown to reverse OIS and thus reduce the risk of central retinal artery occlusion. If the carotid artery is 100% blocked, endarterectomy may not be effective because of the risk of embolism formation from the procedure. Carotid artery bypass has been shown to cause regression of OIS but has not been shown to have a long-term positive effect on visual acuity outcome. Panretinal photocoagulation to the involved retina has been shown to cause regression of the iris neovascularization but is not as effective for this purpose as when it is used in diabetic retinopathy.

CONNECTIVE TISSUE DISEASES

Connective tissue diseases, also known as collagen vascular diseases, are a group of disorders of unknown etiology that are characterized by arthritis, vasculitis, and autoimmunity. The ocular findings of these diseases are not specific, although some characteristics may help in the differential diagnosis of these diseases.

Giant Cell Arteritis

Typically a disease of the elderly, giant cell arteritis (GCA) rarely occurs in patients younger than 60 years. In this disorder, a cellular infiltration occurs of the walls of mediumto large-sized arteries throughout the body. This process produces the symptoms of neck, shoulder, and joint pain. If the superficial temporal artery of the head is involved, then fever, headaches, temporal scalp pain, and jaw claudication can result. Any elderly

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patient with temporal scalp pain should have an immediate erythrocyte sedimentation rate (ESR) performed. An elevated ESR in light of these symptoms strongly suggests GCA. A temporal artery biopsy will confirm the diagnosis of GCA. The patient may experience a concurrent loss of vision resulting from posterior ciliary artery involvement, causing a classic anterior ischemic optic neuropathy (ION) of the optic nerve head, or central retinal artery occlusion (CRAO), causing a cherry-red spot. Classically, the nerve head is swollen and peripapillary hemorrhages and CWS are present on the involved side, although the retina may be minimally involved. The patient complains of a loss of vision in the involved eye. Visual field testing commonly reveals an altitudinal field defect, and external tests usually demonstrate a relative afferent pupillary defect on the involved side. Treatment of GCA should commence immediately on discovery of an elevated ESR in an elderly patient with any of the signs or symptoms described above. Once treatment is started, a temporal artery biopsy may be performed to confirm the diagnosis. Immediate treatment is the key to prevent further vascular occlusions and reduce the risk of profound loss of vision on the contralateral side, however. Treatment consists of high-dose oral prednisone (80 to 120 mg daily). Initial treatment may commence with intravenous steroids (1 gram daily for 3 to 5 days) followed by the high-dose oral steroids. Treatment is necessary for at least a year to keep the ESR and C-reactive protein normalized.

Wegener ’s Granulomatosis

In this disorder, a granulomatous vasculitis of the upper and lower respiratory tracts, kidneys, and other organ systems occurs. The disease can occur anytime from childhood on, and the mean patient age at onset is 40 years. It is typified by granulomas that form anywhere in the respiratory tract from the nose to the lungs. Wegener’s is autoimmune in nature, with antibody and cell-mediated complexes contributing to the tissue damage. Patients usually are seen with respiratory symptoms and paranasal pain and discharge. Laboratory findings indicate kidney involvement in 85% of cases, with an elevated ESR and C-reactive protein, a positive rheumatoid factor, and an elevation of immunoglobulin G (IgG) gamma globulin. The patient will usually complain of fever and malaise. Ocular findings will be present in 50% of patients, including orbital disease with optic nerve compression yielding a loss of visual acuity, extraocular muscle palsies with resultant diplopia, and optic nerve vasculitis with disc edema, hemorrhages, and ischemia. Treatment consists of the use of cyclophosphamide (for cytotoxic treatment) to stop the disease and improve the quality of life. Corticosteroids may also be

used for as long as 6 months to limit ocular tissue damage and reduce optic nerve compression to restore visual acuity.

Systemic Lupus Erythematosus

Systemic lupus erythematosus (SLE) is characterized by a derangement of the immune system that causes an exaggeration of antibody production. It is idiopathic, multisystem, and is typified by exacerbations and remissions. As many as 90% of SLE patients are women and the average age of onset is 30 years. SLE can, however, occur at any age. Although it is of unknown etiology, a genetic component definitely exists that seems to be modified by environmental influences. In fact, some drugs have been known to cause SLE. These medications include chlorpromazine, hydralazine, isoniazid, and methyldopa. The onset of the disease is heralded by the production of antibodies that react against cell constituents and have direct toxic effects on target cells. In addition, antibodyantigen immune complexes form and circulate with complement and cause a destructive inflammation to occur in the blood vessel walls. SLE causes cutaneous rashes, such as the classic butterfly malar rash across the bridge of the nose. Inflammatory arthralgias of the joints produce significant pain. Renal disease is a sequela that accounts for a portion of the mortality rate associated with SLE. Patients suspected of having SLE are given a battery of laboratory tests. The presence of four of the eleven SLE laboratory and clinical criteria identified by the American Rheumatism Association establishes the diagnosis. Lupus retinopathy typically occurs in the elderly or the very sick patient with SLE. CWS, hemorrhages, retinal edema, hard exudates, microaneurysms, and retinal vascular occlusive disease characterize this retinopathy. Cranial nerve palsies may also occur, yielding diplopia, ptosis, and a relative afferent pupillary defect. Treatment of SLE consists of nonsteroidal antiinflammatory drugs (NSAIDs) such as aspirin, antimalarial medications (hydroxychloroquine), and systemic steroids. The NSAIDs and antimalarial drugs are useful for the arthralgias and fever, and the steroids reduce the inflammation to various organ systems and control any hematological complications.

Scleroderma

A connective tissue disease of unknown etiology, scleroderma causes fibrous replacement of the skin, vascular insufficiency, and vasospasm. The primary characteristic of scleroderma is thickening of the dermis that ultimately leads to contraction and immobility of the skin. The condition starts peripherally in the fingers and toes and spreads centrally to the arms and

face. Histiologically, an increase in the concentration of collagen occurs in the skin and organ systems. Ultimately, the skin appears taut and shiny.

In addition, an increase in collagen content occurs in the walls of blood vessels. This can lead to Raynaud’s disease, a condition characterized by pallor and tingling after exposure to cold, emotional stress, or vibrating tools. The patient may have difficulty swallowing, because the esophagus becomes dysfunctional, causing gastroesophageal reflux. A major cause of mortality associated with scleroderma is renal disease, leading to malignant hypertension and renal failure.

The most common ocular manifestations of scleroderma include the CWS and intraretinal hemorrhages associated with hypertensive retinopathy. The presence of optic disc edema indicates malignant hypertension caused by renal crisis. External ocular signs include tightness of the eyelids resulting in keratoconjunctivitis sicca. Rarely, extraocular muscle involvement with palsy is present. The ocular signs of scleroderma are usually associated with renal involvement, thus the presence of hypertensive retinopathy in cases of scleroderma warrants a complete renal evaluation.

The treatment of scleroderma is directed toward the associated renal crisis, and includes blood pressure control and renal dialysis. Calcium channel antagonists are useful to control the symptoms of Raynaud’s phenomenon. The systemic sclerosis is difficult to control, although the use of D-penicillamine is of some benefit. Survival rates are improved by using this agent. Systemic steroids have not been shown to be effective in the treatment of scleroderma.

Rheumatoid Arthritis

Prevalence in the population of as much as 2.0% makes rheumatoid arthritis (RA) the most common of all collagen-vascular diseases. RA is characterized by an insidious onset of a symmetrical, deforming polyarthritis, mostly of the hands and feet. The bones at the joints become eroded with eventual destruction. RA is characterized by morning stiffness, arthritis of at least three joints simultaneously and symmetrically, and a positive rheumatoid factor (RF). Radiology helps to confirm the diagnosis.

The ocular involvement in cases of RA includes keratoconjunctivitis sicca, Sjögren’s syndrome, episcleritis, and scleritis. The scleritis may be anterior, posterior, or necrotizing. Scleritis occurs in 1.0% of patients with RA. In patients with scleritis, as many as one third have RA. The cornea in RA patients may exhibit a benign or necrotizing marginal furrow.

Posterior segment involvement is rare, although in some cases of RA CWS have been noted and are responsive to oral corticosteroids.

Treatment of RA includes the antimalarial medications chloroquine and hydroxychloroquine, which display antiinflammatory effects. Usually, treatment begins with nonsteroidal antiinflammatory drugs (e.g., aspirin, indomethacin, and naproxen), proceeds to slow-acting antirheumatic drugs (e.g., gold, hydroxychloroquine, and D-penicillamine), low-dose prednisone, and finally, methotrexate. RA-associated anterior scleritis is treated with indomethacin, and posterior scleritis is treated with systemic corticosteroids.

The treatment of RA patients with the antimalarial drugs chloroquine or hydroxychloroquine mandates a posterior evaluation twice yearly to monitor for the formation of a “bull’s-eye” pigmented retinopathy. This maculopathy is caused by an accumulation of these antimalarial drugs in the macula and is considered a potentially harmful sequela of toxicity to the medications. The biannual exam should evaluate for any reduction in visual acuity, any visual field loss by using a macula test with red stimulus, color vision changes, Amsler grid changes, and funduscopy. Early detection of a pigmentary maculopathy can lead to a reversal of the condition on discontinuation of the medication, but if ocular toxicity is detected late it may be irreversible and cause permanent visual changes.

Polyarteritis Nodosa

Polyarteritis nodosa (PAN) is a multisystem, necrotizing inflammatory disease that causes a vasculitis of the smalland medium-sized arteries. PAN is characterized by the deposition of immune complexes in the walls of the blood vessels, particularly at the sites of branching and bifurcation. Mean patient age at onset is 45 years, and males are 2.5 times more likely to be affected than females. All layers of the vessel wall demonstrate polymorphonuclear leukocytic infiltration that result in edema and necrosis. As the vessel wall thins and weakens, an aneurysm develops that can rupture and cause tissue necrosis. Vascular occlusion can also result from the deposition of immune complexes in the anterior wall.

PAN most often affects the heart, kidneys, liver, gastrointestinal (GI) tract, CNS, and skin. At first the clinical symptoms include fever, weight loss, malaise, headache and abdominal pain. PAN can result in renal and heart failure and arthritis. Laboratory tests demonstrate leukocytosis and an elevated ESR.

Of PAN patients, 10% demonstrate ocular manifestations of the disease. In some cases, the earliest sign of PAN is exophthalmos and orbital pseudotumor. A PAN-associated scleritis may lead to a retinal detachment. The most common ocular finding in PAN is choroidal vasculitis. When the retinal vessels become involved, a resultant retinopathy is produced that is characterized by edema, vasculitis, CWS, hemorrhages,

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and exudates. Ultimately, retinal vascular occlusions can occur that lead to neovascularization. Choroidal vascular involvement can cause TIAs, ION, disc edema, and optic nerve head hemorrhages.

PAN can be fatal, usually caused by kidney disease, myocardial infarction, congestive heart failure, liver failure, bowel perforation, or CVA. Treatment of PAN with oral steroids may yield symptomatic relief and increase survival rates. Combining steroids with immunosuppressive agents has dramatically improved the prognosis of the disease.

tration of white blood cells in the walls of the retinal vessels. This takes on the appearance of the classic “candle-wax drippings,” causing the vessel to be encased in a white sheath (Figure 22-2). Other posterior manifestations of sarcoidosis include “snowballs” along the pars plana, retinal neovascularization, and vitreous hemorrhages (Figure 22-3). Cream-colored nodules indicative of sarcoid granulomas may invade the retina and optic nerve. Disc edema may occur in cases of nodular invasion of a single optic nerve, and papilledema may result from granulomatous deposition within both nerves of the brain.

SARCOIDOSIS

This multisystem, granulomatous disease of unknown etiology is considered an inflammatory condition because no known etiologic factor has been isolated. It is thought that airborne antigens are inhaled and stimulate a granulomatous response in the lungs. Antigens then spread through the bloodstream to all organ systems, including the eye, and can cause a wide range of inflammatory responses. Almost one third of all ocular sarcoidosis involves the posterior segment. Typically, a disseminated chorioretinitis will be present (Figure 22-1), and in active conditions an accompanying overlying vitritis will occur. Pathognomonic of ocular sarcoidosis is a periphlebitis caused by an infil-

A

C

INFECTIOUS DISEASES Bacterial Infections

Tuberculosis

Caused by the acid-fast bacterium Mycobacterium tuberculosis, tuberculosis (TB) cases are increasing because of by the rise of HIV-infected individuals, who act as a reservoir for infectious diseases. TB most commonly affects the pulmonary system, although any organ system may become involved. The initial infection can cause a fever with coughing and upper respiratory symptoms. Reinfection leads to devastating episodes of night sweats, recurrent fevers, weight loss, and photophobia.

B

FIGURE 22-1 ■ A and B, Funduscopic presentation of creamcolored, subretinal lesions associated with sarcoid choroiditis. C, Fluorescein angiography shows late staining of the choroidal granulomas. (Courtesy Leonard V. Messner.)

FIGURE 22-2 ■ A sheathed retinal vessel in a case of ocular sarcoidosis taking on the appearance of “candle-wax drippings.” (Courtesy Leonard V. Messner.)

the site of infection. When the disease progresses to its secondary stage, the patient experiences flu-like symptoms and, possibly, photophobia from uveitis. In its tertiary stage, cardiac involvement may occur with neurologic changes caused by spread of the spirochete to the cerebrospinal fluid.

In congenital syphilis, a resultant salt-and-pepper fundus can be caused by RPE inflammation and optic atrophy. Acquired syphilitic retinopathy includes posterior scleritis, retinal vascular occlusions, retinitis, and cystoid macular edema (Figure 22-4).

Laboratory tests for syphilis include the fluorescent treponemal antibody absorption (FTA-ABS) or microhemagglutination (MHA-TP), and the rapid plasma reagin (RPR), or venereal disease research laboratory (VDRL). The treatment of syphilis includes the use of penicillin or, if allergy is an issue, then doxycycline or erythromycin.

TB can cause a chronic granulomatous uveitis with vitreous opacities, vitritis, choroiditis (with yellow choroidal lesions), and infectious optic neuropathy. The optic neuropathy consists of tuberculoma lesions of the meninges, optic nerves, or optic nerve head. Laboratory tests include a chest x-ray, Mantoux test (injection of denatured TB bacteria) as part of a PPD (purified protein derivative) anergy panel, and sputum cultures.

Once the diagnosis is confirmed, treatment consists of pyrazinamide, rifampin, and isoniazid daily for 2 months, and rifampin and isoniazid for 4 additional months. Ethambutol may also be used in conjunction with this treatment. Corticosteroids and vitamin B6 supplements may be part of the therapeutic regimen.

Syphilis

Treponema pallidum is a highly infectious spirochete that is spread by sexual contact. In the primary disease, formation of a painless chancre occurs, usually at

Lyme Disease

Like syphilis, Lyme disease is caused by a spirochetic infection by Borrelia burgdorferi, and is usually transmitted by the bite of an infected Ixodes tick. The ticks feed on the white-footed mouse and the white-tailed deer, and these, as well as other animals, act as reservoirs for the spirochetes. The ticks are disseminated through much of the world by migratory birds.

Like syphilis, untreated Lyme disease has three stages. In the earliest stage the patient may have a skin rash and flu-like symptoms for as long as a month after the bite. In stage two, there may be multiple skin lesions, joint pain, uveitis, pericarditis, and a stiff neck for 1 to 6 months after the bite. In the third stage, 6 months to years after the bite, the disease becomes chronic. The spirochete infection involves the knee joints, causing pain, and the CNS, causing memory loss, dementia, and multiple sclerosis (MS)–like symptoms.

Posterior involvement most often is seen as a pars planitis (intermediate uveitis), characterized by “snowballs” along the pars plana, and an associated vitritis.