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

308 THE EYE IN SYSTEMIC DISEASE

FIGURE 21-14 ■ Posterior subcapsular cataract in a patient on long-term use of corticosteroids for chronic uveitis.

Vitreous

White blood cells arise in the vitreous from the choroid, retina, and ciliary body. Protein can also leach into the vitreous, producing a haze. Vitreous haze is a better indicator of inflammation than cells are and is best seen in a binocular indirect view. Inflammation of the vitreous, or vitritis, indicates a posterior extension of the uveitis, and is therefore more likely to be associated with a systemic disease. The classic appearance of a vitritis is that of a “headlight in a fog,” because the yellow optic nerve head surrounded by a pinkish-red blurry fundus weakly reflects the examiner’s light. Typically, little or no fundus detail can be visualized through the hazy vitreous.

Retina

The deposition of accumulations of white blood cells along the pars plana is known as “snowballs” and is often associated with systemic diseases, particularly Lyme disease. This form of intermediate uveitis is often found concurrent with anterior uveitis.

The snowballs are best seen with a binocular indirect ophthalmoscopic evaluation of the fundus. Snowballs have also been reported with uveitis secondary to tuberculosis.

Sheathing of the peripheral retinal vessels reflects an inflammatory response within the vessel walls. The presence of sheathed retinal vessels associated with an anterior uveitis increases the likelihood of a systemic disease, particularly syphilis or sarcoidosis. In the case of sarcoid, the vessels take on the classic appearance of “candle-wax drippings.”

Optic Nerve Head

Disc hyperemia, papillitis, and papilledema can be associated with anterior uveitis. The finding of any of these optic nerve head changes greatly increases the likelihood of the anterior uveitis being associated with a systemic disease. For example, sarcoidosis can directly affect the nerve head, which may swell, either

because of granulomatous deposition within the optic nerve or an increase in intracranial cerebrospinal fluid pressure (Figure 21-15).

TREATMENT OF ANTERIOR UVEITIS

The medical intervention required to treat anterior uveitis is guided by three goals. The first and foremost goal is the reduction and eventual elimination of the intraocular inflammation. Timely intervention reduces the chance of serious complications such as massive KP formation, cataract, glaucoma, and permanent visual reduction.

The second goal involves the mitigation of the pain and photophobia associated with anterior uveitis. The ocular irritation associated with intraocular inflammation is of significant concern and should not be overlooked. Symptomatic relief is an ethical imperative of appropriate therapeusis. The alleviation of photophobia also helps promote the doctor-patient interpersonal relationship and improves compliance.

Finally, the clinician must attempt to prevent formation of posterior synechiae and break any existing adhesions. This reduces the possibility of permanent pupil dysfunction and prevents future episodes of pupillary-block glaucoma.

Mitigation of Inflammation

Amelioration of the inflammatory response is the primary goal of uveitis therapy. The inflammatory response of anterior uveitis is an undesirable derangement of the immune response that can lead to permanent intraocular scarring and visual loss. By quelling this exaggerated response, the risks of such complications are greatly reduced.

In the natural world, anterior uveitis evolved as a way to protect the eyes and body from invasion by

FIGURE 21-15 ■ Papilledema in a case of sarcoidosis. Note the blurry margin of the disc.

dangerous pathogens. Intraocular organisms could easily invade the bloodstream to infect all parts of the body. Any sight-threatening complication of the anterior uveitis was overridden by the potential life-saving response of the ocular immune system. Modern medical intervention makes obsolete this hairpin response by the iris and ciliary body. Anterior uveitis no longer is considered an advantageous immune response, because it can cause such devastating ocular complications. Therefore, treatment of anterior uveitis reduces the risk of such complications without an associated rise in morbidity or mortality.

The anterior uveitis response is characterized by iris and ciliary body blood vessel dilation, degranulation of mast cells with bradykinin and histamine release, and lymphocyte proliferation. Topical corticosteroid eyedrops act to reduce the intraocular inflammation by stabilizing both the capillary bed and the mast cell membrane and reducing white blood cell proliferation.

Typically, therapy with topical steroid drops is started by using one drop every hour on the first day as a loading dose in the affected eye. On the second day, this schedule is usually tapered to every other hour during waking hours. On the third day, as some cellular clearing is usually observed in the anterior chamber, the drop is titrated to four times daily. The steroid drop is tapered slowly during the next 2 to 3 weeks.

Topical corticosteroids run the risk of glaucoma, cataract formation, and poor corneal wound healing. The patient should be monitored for these complications during the course of the treatment at least once weekly.

Oral steroids have been used in some profuse anterior uveitis reactions, but are usually not necessary.

Symptomatic Relief

Photophobia is of primary concern to the patient. This aversion to light is a symptom usually not previously experienced and can be frightening to the patient. Photophobia is stressful and typically overrides all other concerns of the patient.

Photophobia is produced by the biochemical cascade that is responsible for the inflammatory response of the eye. As the iris swells, the threshold to pain of the iris nerve is reduced. Any movement of the iris will now produce pain. When the eye is exposed to light, the pupil quickly constricts and the irritation and pain that results can be unbearable.

Photophobia may have evolved to play a role in the adaptive response of the organism to intraocular inflammation. An organism challenged with such inflammation responds to photophobia by seeking out a dark environment, thus allowing for pupil dilation and iris stability. This in a sense produces a natural cycloplegia without pharmacological blockade of the pupil and helps speed the resolution of the uveitis.

Cycloplegia acts to paralyze the sphincter muscle by use of a parasympatholytic agent that renders the iris immobile and dilated. Preventing movement of the iris ameliorates photophobia, and the patient is provided with symptomatic relief.

Pain can help initiate the inflammatory response, and although cycloplegia does not exert an antiinflammatory effect, the reduction in photophobia may prevent an exacerbation of the uveitis.

The spectrum of cycloplegic agents runs the gamut from 1.0% tropicamide (Mydriacyl) , an effective dilator but poor cycloplegic agent, to 1.0% atropine, a poor dilator but the most effective of all cycloplegic agents. The best choice of cycloplegic agents is 0.5% homatropine, a topical medication affording both excellent dilation and cycloplegic effects. Atropine provides for superb cycloplegia, but immobilizes the pupil in the middilated position. In this position the iris is closest to the anterior lens capsule, where it is most vulnerable to pupillary block and posterior synechiae formation.

In most cases of anterior uveitis, the appropriate cycloplegic agent is homatropine 5.0%, used twice daily. It may be stopped without tapering once clearance of the anterior chamber cells is appreciated. Usually this occurs with treatment in 3 to 4 days. Atropine is often used in acute iritis with a profuse cellular response that is accompanied by fibrin or hypopyon production, but in such cases a topical sympathomimetic should be used concurrently to provide maximal pupillary dilation.

Posterior Synechiae Intervention

Posterior synechiae represent an abnormal adhesion between the iris and lens. The further away the iris is from the anterior lens surface, the less the chance of synechiae formation. The iris is furthest from the lens when it is in the dilated position.

Mydriasis is provided by stimulation of the iris dilator muscle with a sympathomimetic medication. Topical 2.5% phenylephrine is most often used twice daily to accomplish the goal of preventing posterior synechiae formation. The medication is usually discontinued as soon as cellular clearing is observed in the anterior chamber; the dilating agent need not be titrated.

Posterior synechiae may be broken by use of 2.5% or 10.0% topical phenylephrine within 3 days of formation. Thereafter it becomes more difficult to break existing synechiae. The 2.5% formulation of phenylephrine has a lower success rate of breaking existing synechiae, but is a safer medication to use than the more potent 10.0% formulation. However, 10.0% phenylephrine may have significant cardiogenic side effects, including tachycardia, and is associated with more adverse sequelae than the 2.5% concentration. Because of these untoward side effects, 10% phenylephrine is safest

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when used only in the office. Punctal occlusion will limit systemic absorption of this potent sympathomimetic medication and minimize the potential of an adverse reaction.

Resistance to Treatment

With treatment, cell clearing from the anterior chamber usually can be observed within 3 days of the initiation of drops. Most cases of uveitis resolve completely in 2 to 3 weeks. Resistance to drug therapy causes an extension of the clearing time, with persistence of photophobia and cells well past a month. The uveitis should be considered chronic if it persists past 6 weeks despite treatment. Resistance to drug therapy is a strong indicator of an underlying systemic disease as a cause of the anterior uveitis.

When the anterior uveitis is becoming obviously chronic, an alternative to topical steroid drops is the use of a periocular corticosteroid injection. This method permits a relatively high concentration of steroid to be given rapidly. Adverse sequelae to this route of administration include accidental globe perforation, proptosis, and fibrosis of the extraocular muscles, severe glaucoma, and the need in children to perform this procedure under general anesthesia.

Although oral steroids have been used concurrently with topical steroid drops in the treatment of anterior uveitis, it is doubtful that systemic corticosteroids play a significant role in the amelioration of intraorbital inflammation. Higher concentrations of steroid are achieved in the eye by use of topical drops than by oral administration. Systemic corticosteroids are the initial drug of choice, however, when treating severe bilateral idiopathic uveitis that is threatening the sight of the patient. In these cases, the treating clinician should make every effort to rule out the possibility of malignant disease or infection as a cause of the anterior uveitis. In addition to this instance, an anterior uveitis caused by Behçet’s disease is most effectively treated with oral steroids (Figure 21-16).

Recurrent Anterior Uveitis

An anterior uveitis that recurs after cessation of treatment is at a higher risk of being associated with a systemic disease than a single episode of intraocular inflammation.

Recurrent anterior uveitis requires more aggressive treatment and a longer duration and tapering of topical corticosteroids than a first-time presentation. In general, the reappearance of anterior uveitis demands a longer treatment period, often twice as long, as the initial case. In recurrent cases tapering of the steroid is prolonged by many more weeks and compliance by the patient becomes a serious issue.

FIGURE 21-16 ■ Behçet’s syndrome. Several painful ulcers on the tongue. These may be recurrent for years. (From Cawson RA, et al: Pathology: the mechanisms of disease, St Louis, 1989, Mosby Year-Book.)

Recalcitrant cases of anterior uveitis may require a low-dose daily regimen of one drop of topical steroid every day or every other day for the rest of the patient’s life in order to quell the inflammation. Every attempt should be made in these cases to ascertain the underlying cause of such chronic inflammation.

ANTERIOR UVEITIS AND SYSTEMIC DISEASE

Systemic Disease–Related Uveitis Characteristics

Any recurrent anterior uveitis should be suspected of having an associated systemic disease as an underlying cause.

First-time cases of intraocular inflammation may have tell-tale primary characteristics that raise the suspicion of systemic disease and instigate laboratory investigation. These characteristics include a uveitis that extends into the posterior chamber, is chronic in nature, bilateral, and resistant to treatment.

Secondary characteristics include the presence of granulomatous keratic precipitates, hypopyon, iris nodules, posterior synechiae, posterior chamber cells, “snowballs” on the pars plana, macular edema, and disc edema. In addition, the presence of any systemic symptoms such as fever, joint pain, malaise, and lymphadenopathy concurrent with uveitis raises the suspicion of systemic disease.

General Disease Classification

Nine systemic diseases are far more commonly associated with anterior diseases than all others. These nine are classified into three groups of diseases: the collagen-

vascular diseases, the inflammatory diseases, and the infectious diseases (Table 21-1).

The collagen-vascular diseases are a group of disorders characterized by the presence of joint pain and inflammation, the underlying cause of which is typically idiopathic, although infectious sources have been identified for certain rheumatological entities. Typical of many of the collagen-vascular diseases that cause uveitis is the presence of the HLA-B27 haplotype. These disorders include ankylosing spondylitis, Reiter’s syndrome, juvenile rheumatoid arthritis, and Crohn’s disease. The characterization of diseases is complicated by shared characteristics and etiologies. For example, Lyme disease is a non–HLA-B27 infectious disease caused by a bacterium, but it can cause significant collagen-vascular joint pain and inflammation.

The second class of anterior uveitis-related systemic disease includes the inflammatory conditions of sarcoidosis and Crohn’s disease. These conditions have no known infectious source and are of unknown etiology, but have inflammation as the primary pathologic characteristic. Note that Crohn’s disease can be considered both an inflammatory condition of unknown etiology, and an HLA-B27–related disorder.

The third class of disorders is infectious diseases. The most common infectious diseases that cause anterior uveitis are tuberculosis, Lyme disease, syphilis, and the herpes viruses.

Collagen-Vascular Diseases

Ankylosing Spondylitis

A collagen-vascular, HLA-B27–related disease, ankylosing spondylitis (AS) is characterized by inflammation of the sacroiliac joints, total spinal fusion, back pain and stiffness. AS typically occurs in white males, 20 to 40 years of age, who early in the course of the disease begin to notice lower back pain. Early diagnosis and treatment is essential to prevent permanent spinal deformity. Of patients with AS, 25% have some sort of ocular involvement, including iritis. The inflammation is typically acute, unilateral, painful, and confined to the anterior chamber. There may be fibrin deposition with development of a hypopyon. The pupil may become occluded with a fibrous membrane and visual acuity may drop to light perception (Figure 21-17). Ocular treatment frequently involves the use of topical atropine with dilating agents and topical corticosteroid drops. Because 96% of patients with AS have the HLAB27 antigen, laboratory testing for this haplotype is essential. Other laboratory tests for AS include radiographs for the sacroiliac joints to rule out sacroiliitis, and rheumatoid factor, which should be negative. Treatment of AS includes nonsteroidal antiinflammatory drugs (NSAIDs) and physical therapy. Any patient who is seen with an anterior uveitis and lower back pain should be screened for AS.

Reiter’s Syndrome

An HLA-B27 disorder, Reiter’s syndrome (RS) is characterized by arthritis, uveitis, and urethritis. RS occurs most often in white males aged 20 to 40 years. Dermatological lesions may erupt on the skin in association with RS. The most common location of the arthritis in RS is the wrist and ankles. The diagnosis is made on the basis of the clinical signs associated with a positive HLA-B27 test. The uveitis is treated with topical agents and is usually fairly mild, although corneal “meltdown’” has occurred in some cases. The systemic condition is controlled with NSAIDs and immunosuppressive therapy. Any patient with an anterior uveitis and distal joint pain should be screened for Reiter’s syndrome.

Juvenile Rheumatoid Arthritis

The diagnosis of juvenile rheumatoid arthritis (JRA) is made on the basis of the presence of arthritis in a child younger than 16 years with no known etiology. There is usually a negative rheumatoid factor (RF) test. Several subclassifications of JRA exist, but in general young girls are much more susceptible to the disease than young boys. The most commonly inflamed joint in JRA is the knee, although children may not complain of pain. Usually a significant asymmetry will be noted when the appearance of the two knees is compared. Laboratory tests, including joint film, RF, ANA, and a WBC will help confirm the diagnosis. Of boys with pauciarticular JRA, 75% are positive for the HLA-B27 antigen, and girls tend to be negative for this antigen. Treatment of JRA may include systemic steroids and surgery. The highest risk of anterior uveitis in JRA occurs in girls with pauciarticular arthritis who test positive for ANA. The anterior uveitis associated with JRA is typically chronic and asymptomatic. The uveitis is often picked up on routine examination, by which time severe intraocular damage has already occurred. Usually no conjunctival injection is present, but a cellular anterior chamber response has caused posterior synechiae formation and pupil distortion (Figure 21-18). A band-shaped keratopathy occurs in more than half the patients, and may lead to visual disturbance (Figure 21-19). Cataract and glaucoma can result in chronic JRA-related uveitis. Topical corticosteroids are the mainstay of treatment and young JRA patients need to be seen every 3 to 4 months. Intraocular injections of steroid may be needed to quell the intraocular inflammation, but general anesthesia is necessary in children to accomplish this procedure. Oral steroids should be avoided in children for JRA-related uveitis, because these drugs have overwhelming side effects on bone growth. Eventual cataract extraction may be needed to allow for appropriate visual stimulation and prevention of amblyopia in the arthritic child. Of all patients with severe JRA-associated iridocyclitis, three quarters

demonstrate a band-shaped keratopathy. The keratopathy can be removed with chemical chelation. The excimer laser may play a role in removal of the bandshaped keratopathy in the future. Every child with anterior uveitis must be screened for JRA.

Inflammatory Diseases

Sarcoidosis

Sarcoid is a multisystem granulomatous disease of unknown etiology. This disease can affect almost any organ system in the body, although the usual involvement

is the lungs and skin. The highest incidence of sarcoid in the world is found in Sweden. In the United States, an even higher level is found in African-Americans, but a very low rate is found in the white population. Commonly in the United States, the sarcoid patient will be a young, African-American female, aged 20 to 40 years, who is often asymptomatic. If systemic symptoms are present, most patients with sarcoid present with coughing, fever, fatigue, and weight loss. Laboratory tests for sarcoid include, among others, a chest x-ray (demonstrating a hilar adenopathy), gallium scan, angiotensin-

converting enzyme (ACE), serum lysozyme, and a positive skin (Figure 21-20) or lung biopsy. Of sarcoid patients, two thirds develop anterior uveitis, typically an acute iridocyclitis. The intraocular inflammation is characterized by granulomatous keratic precipitates and iris nodules. Eventually, peripheral retinal blood vessel sheathing, a white inflammatory response known as “candle-wax dripping,” may occur. The uveitis may be associated with disc edema or papilledema, as granulomatous sarcoid nodules invade the optic nerve or interfere with cerebrospinal fluid drainage. Often, sys-

temic sarcoid does not require treatment unless significant symptoms are present. Corticosteroids are the mainstay of treatment for both systemic and ocular sarcoid. Any patient with anterior uveitis who has a chronic cough should be evaluated for sarcoidosis.

Crohn’s Disease

Of patients with Crohn’s disease, 50% are HLA-B27 positive. This inflammatory bowel disorder has been associated with the deposition of granulomatous nodules from the tongue to the rectum. The uveitis associated

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FIGURE 21-17 ■ Acute plasmoid iridocyclitis in a patient with ankylosing spondylitis. Note the high fibrin content on the aqueous around the pupil.

FIGURE 21-18 ■ Iridocyclitis in a patient with juvenile rheumatoid arthritis revealing a “white” pupil caused by a cataract and a distorted pupil secondary to posterior synechiae.

FIGURE 21-19 ■ Band keratopathy. Calcium deposits in Bowman’s layer of the cornea in juvenile rheumatoid arthritis.

with Crohn’s disease may be granulomatous in nature and have characteristic “mutton fat” KP deposition. Diagnosis of Crohn’s disease involves upper and lower GI series, sigmoidoscopy, endoscopy, barium enema testing, hypoproteinemia on blood testing, and symptomology. Any anterior uveitis patient with a history of recurrent diarrhea, bloody diarrhea, or abdominal cramping should be evaluated for Crohn’s disease.

Infectious Diseases

Tuberculosis

An infectious disease, tuberculosis (TB) is spread by aerosolized droplets that contain Mycobacterium tuberculosis. Inhalation of the bacteria causes a short-lived asymptomatic and self-limited pneumonia. Healing occurs with formation of pulmonary granulomas that calcify and remain inactive. Reactivation of the disease occurs with a second challenge of bacteria, other disease states or age. Approximately 1% of TB cases develop ocular manifestations, and granulomatous anterior uveitis may occur. Diagnosis of TB can be difficult to make and includes a chest x-ray, purified protein derivative (PPD) skin test, and sputum culture. Treatment of systemic TB includes regimens of isoniazid and rifampin for 9 months, with a third drug such as ethambutol for the first 3 months. TB should be suspected in any patient with an anterior uveitis coincident with a chronic cough.

Syphilis

Syphilis is still the most common of all the treponemal infections and the most significant seen in the optometrist’s office. The infection is caused by the spirochete Treponema pallidum and is transmitted exclusively by sexual contact. Syphilis is characterized by three stages: primary syphilis (stage one) characterized by a chancre, secondary syphilis that often presents with a generalized rash (Figure 21-21), and tertiary, or cardiovascular or neurosyphilis. Syphilis is contagious in the untreated primary or secondary stages, especially if there is mucocutaneous involvement. Late secondary or tertiary syphilis tends not to be infectious. The spirochete cannot live long outside the body and can penetrate intact mucous membranes or abraded skin. The average incubation period is 3 weeks, but can last from 1 week to 3 months. The infection spreads throughout the body through the lymphatic system to the bloodstream. In the eye, anterior uveitis occurs in the secondary and tertiary stages of syphilis. The inflammation of secondary syphilis is typically an iridocyclitis with iris nodules. Laboratory screening for syphilis include the venereal disease research laboratory (VDRL) or rapid plasma regain (RPR) tests. Treponemal tests to confirm any positive screening result include the T. Pallidum immobilization test (TPI) and the more com-

FIGURE 21-21 ■ Syphilis. Maculopapular rash of the palms is suggestive of syphilis. (From Cawson RA, et al: Pathology: The mechanisms of disease, St Louis, 1989, Mosby-Year Book.)

mon fluorescent treponemal antibody absorption (FTA-ABS) test. The TPI is expensive, and the microhemagglutination (MHA-TP) test is used less frequently than the FTA-ABS test. Penicillin is the mainstay of treatment in all cases of syphilis, although the amount and route of administration depends on the stage of the infection. In all cases of syphilis, the possibility of coinfection with HIV must be ruled out. Patients with anterior uveitis who have a coincident skin rash should be evaluated for syphilis.

Lyme Disease

This bacterial infection is caused by Borrelia burgdorferi, a tick-borne spirochete similar to T. pallidum. The spirochete is most commonly found in the Ixodes ticks, whose host is frequently the white-footed mouse (in its larval stage), or white-tailed deer (in the adult stage).

Similar to syphilis, the clinical manifestations of Lyme disease are divided into three stages. Stage I involves a local reaction to the tick bite with an accompanying oval erythematous rash that persists for a month. Stage II comprises a disseminated response to any organ system with a host of signs and symptoms, including cardiac and neurological complications. Stage III involves the development of arthritis, chronic fatigue, and dementia. Laboratory confirmation of an infection includes the immunofluorescent assay test (IFA) and enzyme-linked immunosorbent assay test (ELISA) with a confirmatory Western blot test. Laboratory testing still lacks sensitivity in diagnosing Lyme disease and the results should be integrated with the history and clinical signs and symptoms. An FTA-ABS should be used to rule out syphilis as part of the differential diagnosis. The treatment of Lyme disease includes the use of an antibiotic such as oral tetracycline, doxycycline, or amoxicillin. In severe cases, intravenous ceftriaxone or penicillin may be used if prolonged treatment is anticipated. The anterior uveitis associated with Lyme disease is typically an intermediate uveitis or an iridocyclitis with an associated pars planitis. Inflammatory deposits will occur along the pars plana that take on the appearance of “snowballs’” which may rise and fall in the vitreous when the patient looks up and down. Treatment of the anterior segment inflammation caused by Lyme disease consists of topical corticosteroids and cycloplegic agents. Lyme disease should be suspected in any patient with anterior uveitis, particularly a pars planitis, with an associated rash.

Herpes Zoster Ophthalmicus

A DNA herpes virus, herpes zoster ophthalmicus (HZO) remains latent in the ganglia after a patient has had a bout of chickenpox. After reactivation, caused

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by secondary infection, environmental stress, or age, the virus travels along the ophthalmic division of the trigeminal nerve. The hemicranial, cutaneous outbreak is vesicular in nature and extremely painful. The lesions are fluid-filled and erupt onto the surface of the skin. Eventually, the skin lesions scab over, become crusty, and flake off the skin surface. Superficial permanent scarring of the skin may result from a single outbreak and cause anxiety and depression in individuals. Postherpetic neuralgia can result in intractable pain after an episode of HZO and require the use of pain-killing medications and antidepressants on a long-term basis. The typical corneal lesion in HZO is a stromal keratitis. HZO can cause vascular occlusion and secondary ischemia of the iris that leads to anterior uveitis. The iris may reveal patchy atrophy that is associated with ischemic areas. Severe ischemia of the iris and ciliary body may lead to phthisis bulbi. The intraocular inflammation associated with HZO keratitis is typified by large KPs and posterior synechiae that develop within 1 to 2 weeks. Histological studies confirm a granulomatous response of the iris and ciliary body. Treatment of HZO should be started within 3 days of the outbreak of HZO with use of oral acyclovir or famciclovir, to reduce virus proliferation, lower the risk of complications, and ease the accompanying intraocular inflammation. Oral antivirals will not mitigate anterior uveitis late in HZO, however, because prolonged intraocular inflammation is caused by ischemia and not viral proliferation. If iris and ciliary body ischemia are present topical corticosteroids and cycloplegic agents may be needed for months to ameliorate the anterior uveitis. Therefore, HZO should be suspected in any patient with anterior uveitis with an associated keratitis and skin outbreak.

Herpes Simplex Keratouveitis

Herpes simplex keratouveitis (HSV) is the most common ocular disease associated with an anterior uveitis. Some uveitis may occur with the epithelial form of the disease, but nearly all stromal keratitis patients have an accompanying anterior uveitis. The inflammation typically causes a very red, painful, and photophobic eye. Slit-lamp evaluation inevitably demonstrates classic dendritic keratitis of the corneal epithelium. Anterior segment involvement usually involves posterior synechiae, anterior chamber cells and KPs posterior to the corneal opacity. The uveitis may be the result of a secondary inflammatory response to the corneal disease or invasion of the virus into the anterior uvea. HSV is treated with topical antiviral agents such as trifluridine (Viroptic) solution or vidarabine (Vira A) ointment. Topical cycloplegic agents should be used to reduce both the associated photophobia and the risk of posterior synechiae development. A topical corticosteroid,

particularly prednisolone phosphate, has been shown to reduce persistence or progression of stromal keratitis and improve the time of uveitis resolution. Topical steroid therapy should be started after the corneal epithelial disease is resolved, and should only be used in conjunction with topical antiviral agents. The addition of oral acyclovir is not beneficial in patients with stromal keratitis already receiving topical antiviral agents. Any patient with anterior uveitis and accompanying corneal opacity should be evaluated for HSV infection.

When to Suspect Systemic Disease

Some obvious cases of anterior uveitis warrant a suspicion of an associated systemic disease. All cases of bilateral or alternating anterior uveitis should be evaluated for systemic disease. Recurrent uveitis and cases that resist treatment may have an underlying disease that constantly reinforces the intraocular inflammation. A systemic disease may cause a chronic anterior uveitis with persistence of the intraocular inflammation longer than 4 weeks.

Any iritis that subsequently proceeds posterior to involve the ciliary body, pars plana, vitreous, or retina, is highly suspect for an underlying systemic disease. The uveitis itself may indicate an associated systemic disease if large “mutton-fat” KPs, posterior synechiae, hyphema, hypopyon, or iris nodules are present.

The anterior uveitis least likely to have an associated systemic disease is a first-time unilateral acute iritis with significant circumcorneal flush, photophobia, and small KPs. The level of suspicion is much higher in cases of recurrent, bilateral granulomatous iridocyclitis.

The Uveitic History

In all cases of anterior uveitis, a short history can help screen for the presence of systemic diseases. In general, the patient with anterior uveitis should be asked about associated generalized symptoms including headache, fever, neck pain, swollen lymph nodes, sore throat, malaise, or fatigue. Any associated sign raises the possibility of a systemic disease as the underlying cause of the anterior uveitis.

The patient should then be asked about more specific clinical symptoms associated with the uveitis. The presence of lower back pain, particularly in a young, white male, helps screen for ankylosing spondylitis. Wrist and ankle pain, again in a young, white male, may indicate Reiter’s syndrome, especially if an accompanying urethritis is present. Knee pain in a youngster with anterior uveitis, particularly a girl, may indicate JRA, although child abuse must be also considered.

Any pain in the stomach or intestines in a patient with anterior uveitis raises the chances of an associated bowel disorder, particularly Crohn’s disease. Other symptoms and signs to ask the patient about include bloody stools, diarrhea, and abdominal cramping.

The patient should be asked about any episodes of coughing associated with the eye inflammation. Pulmonary involvement in these cases may indicate an underlying tuberculosis infection. Sarcoidosis should also be considered in any uveitic patient who reports a chronic cough as this inflammatory condition primarily involves the lungs.

Any report of a rash associated with a uveitis increases the likelihood of syphilis involvement, no matter at the age of the patient. The typical rash in syphilis is on the palms of the hands, soles of the feet, or across the upper back, and is composed of small, maculopapular, red skin lesions. The rash produced in Lyme disease is distinctly different from syphilis, and is typically a single, silver-dollar-sized oval or annular lesion with quickly expanding borders. Any rash associated with an anterior uveitis increases the likelihood of an associated disease.

Laboratory Testing in Anterior Uveitis

If any likelihood exists of an associated systemic disease on the basis of the history or characteristics of the uveitis, laboratory tests can help pinpoint an etiology. A broad laboratory screening can be performed if the uveitis history does not point to a single disorder. The screening should consist of general blood tests as well as specific serology tests for the most common uveitic entities.

The general blood tests include hematology CBC analysis for the WBC (with a differential), RBC, and platelet levels. An erythrocyte sedimentation rate (“sed” rate [ESR]) will help determine whether any body-wide generalized inflammation is present. A blood chemistry panel, such as the SMA-12, may help ascertain any abnormalities in the patient’s biochemical profile. Urinalysis is an essential screening for renal dysfunction related to the uveitis.

More specific laboratory tests for inflammation include the rheumatoid factor (RF) to rule out rheumatoid arthritis, antinuclear antibodies (ANA) for JRA, HLA-B27 for the collagen-vascular entities, FTA-ABS and RPR for syphilis, Lyme titer (ELISA), ACE for sarcoid, and PPD and chest x-ray for tuberculosis.

The ordering of laboratory tests is often guided by the associated signs and symptoms in a uveitis patient. Unfortunately, a low yield of valuable information is usually found in the history and examination of the intraocular inflammation. Consequently, laboratory testing in cases of anterior uveitis is often undirected

and generalized. In the vast majority of cases of anterior uveitis, laboratory values are normal despite a high suspicion of an underlying disorder. These may represent true undiagnosed systemic disease or a significant insensitivity to the uveitis-associated diseases by established serologic tests.

The ability to diagnose a systemic disease, particularly when the anterior uveitis is the only clinical manifestation of the underlying disorder, allows for early medical intervention, thus minimizing potential complications. This is rewarding for both the patient and clinician, and may preserve the sight and save the life of the patient. However, the inability to diagnose the underlying systemic disease in most cases of anterior uveitis makes this scenario one of the most frustrating in eye care. Sensitivity to the characteristics of uveitis most often associated with an underlying disease, use of the uveitis history, and the frequent use of laboratory tests, should increase the diagnostic yield and permit early medical intervention in cases of systemic disease-related uveitis.

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