Clinical Signs

• Cells and flare in the anterior chamber
  
• Circumcorneal ciliary flush
  
• Nongranulomatous: fine keratic precipitates (KPs) on corneal endothelium
  
• Granulomatous: “mutton-fat” precipitates on corneal endothelium
  
• Iris nodules
  

  Koeppe: clusters of cells on the pupillary border

  
  

  Busacca: cells on the anterior iris surface

  
  

  Berlin: cells in the iris angle structure

  
  
• Miotic pupil
  
• Hypopyon
  
• Hyperemia
  
• Plasmoid iridocyclitis: fibrin with sluggish or no movement of cells in the anterior chamber
  
• Spillover: cells in the anterior vitreous
  
• Low intraocular pressure (IOP) secondary to cyclitis
  
• Elevated IOP secondary to obstruction of the trabecular meshwork, trabeculitis, iris bombè causing pupillary block and angle closure
  
• Cystoid macular edema (CME)
  
• Posterior synechiae
  
• Endothelial dysfunction with associated corneal edema
  
• Fibrin pupillary membrane

Demographics

Anterior uveitis is the most common form of uveitis with an incidence of 9/100,000 people and increasing to 100/100,000 in patients over 65 years of age. Most patients affected are from 20 to 50 years of age. Some forms of anterior uveitis, such as acute nongranulomatous uveitis secondary to ankylosing spondylitis and reactive arthritis (Reiter’s syndrome), are more often found in men. Chronic anterior uveitis is more common in women. Immunologic and hormonal differences are thought to underlie some specific types of uveitis.

Seronegative spondyloarthropathies (rheumatoid factor [RF] negative) that are associated with acute anterior uveitis are often HLA-B27 positive (located on the short arm of chromosome 6). HLA-B27 is positive in 1.4% to 8% of the general population. In patients who present with acute iritis, up to 60% prove to be HLA-B27 positive. Ankylosing spondylitis, reactive arthritis, inflammatory bowel disease (IBD), and psoriatic arthritis are all included in the seronegative spondyloarthropathies.

ABD, is associated with HLA-B51. It is a perivascular inflammation of unknown cause that results in a generalized occlusive vasculitis. The Behçet’s triad includes a hypopyon with iritis, aphthous stomatitis, and genital ulceration. It is less common in the United States and is more common in Japan and Eastern Europe. Researchers in Japan have suggested a diagnostic system that includes major and minor criteria. Major criteria are recurrent oral ulcers, skin lesions, recurrent genital ulcers, and ocular inflammatory disease. Minor criteria include epididymitis, arthritis, vasculitis, gastrointestinal ulcerations, and psychiatric symptoms. Based on the number of criteria, different types have been developed including complete, incomplete, suspect, and possible. Eye findings may include a nongranulomatous anterior uveitis, retinal vasculitis, retinal hemorrhage, macular edema, retinal necrosis, ischemic optic neuropathy, and vitritis. Systemic signs may include erythema nodosum, nondestructive arthritis, IBD, mucous membrane ulcerations, pericarditis, myocarditis, and central nervous system (CNS) strokes.

Lens-associated uveitis or phacoantigenic endophthalmitis is a presumed immune response to lens protein after violation of the lens capsule.

Postoperative uveitis can include infection, lens-associated and intraocular lens (IOL)-associated inflammation. Infectious causes can include Staphylococcus epidermidis, Candida, and delayed endophthalmitis caused by Propionibacterium acnes. Manipulation of the anterior chamber results in some break down of the blood–aqueous barrier (BAB) leading to increased risk of uveitis.

Pseudophakic uveitis may be seen with closed loop anterior chamber intraocular lenses although it is much less common with newer flexible intraocular lens implants.

FHI or Fuchs uveitis syndrome is usually unilateral with varying symptoms of mild discomfort to none. The diagnosis is based on heterochromia, lack of synechiae, and diffusely distributed KPs.

Masquerade syndromes, such as syphilis, may present with an anterior uveitis. Syphilis accounts for 1% to 3% of all uveitis cases. Patients will develop anterior uveitis in 5% to 10% of secondary syphilis cases.

Significant History

• History of ocular trauma or surgery
  
• Recent viral or bacterial disease
  
• History of underlying immunologic disease

Ancillary Tests

Ocular assessment includes visual acuity, pupil testing, IOP, slit-lamp examination, and dilated fundus evaluation.

Laboratory studies: complete blood count (CBC) with differential, erythrocyte sedimentation rate (ESR), chest and pelvis x-ray, Lyme titer, antinuclear-antibody, rapid plasma reagin (RPR) or VRDL, FTA-ABS, purified protein derivative (PPD), human leukocyte antigen (HLA) typing, angiotension converting enzyme, and serum lysozyme.

The Treatment

As the etiology of anterior uveitis is often unknown, treatment is directed to control the inflammation and to prevent damage to uveal vasculature that can result in chronic recalcitrant uveitis or secondary side effects, such as posterior synechiae, cataracts, and glaucoma.

Cycloplegic agents are used to relieve pain, decrease synechiae formation, and reduce the permeability of the iris vasculature. Cyclopentolate or homatropine can be used for mild to moderate inflammation, whereas scopolamine or atropine may be used for more severe inflammation.

Corticosteroids can be applied topically, by periocular injection, systemically, or by intravitreal implants such as fluocinolone acetonide/Retisert (Bausch and Lomb). The steroid therapy should never be stopped abruptly because this may lead to severe rebound in inflammation.

Patients who fail or are intolerant to steroids may require immunomodulatory agents, such as methotrexate or cyclosporine and azathioprine. Recently, tumor necrosis factor-alpha (TNF-α) inhibitors such as infliximab have shown promising results.

Ankylosing Spondylitis

Tammy P. Than

ICD-9: 720.0M

     THE DISEASE

Pathophysiology

Etiology

The etiology is unknown but is thought to be multifactorial. HLA-B27 has been found in 93% of patients with ankylosing spondylitis while present in only 6% of controls. In the absence of HLA-B27, genes for other inflammatory conditions may be important in predisposing individuals. Evidence for this is the greater association with other inflammatory conditions such as Crohn’s disease or psoriasis. Alternatively, bacterial and viral infections may trigger ankylosing spondylitis. In particular, Klebsiella pneumoniae, commonly found in the gastrointestinal tract, is more common in patients with the disease compared to controls. There appears to be a familial pattern as there is a higher incidence of ankylosing spondylitis if there is a positive history in a first-degree relative.

The Patient

Clinical Symptoms

Symptoms usually begin in the early 20s with an onset rarely after the age of 40. Systemic symptoms begin with intermittent hip and/or lower back pain that are worse at night or after inactivity. Bent posture eases the pain, which improves later in the day and with exercise. There may be pain or tenderness in the ribs, shoulder blades, hips, thighs, shins, and heels. The patient may also complain of fatigue, loss of appetite, and general discomfort. Ocular symptoms include pain, redness, and photophobia if uveitis is present.

The disease in women tends to be less severe than in men and may present with neck pain and breast pain in the absence of lower back pain.

Clinical Signs

Uveitis occurs in about 25% of patients with ankylosing spondylitis presenting as an acute, unilateral, nongranulomatous episode. The ocular manifestations may occur prior to joint and skeletal signs, and ankylosing spondylitis accounts for 10% to 33% of all cases of anterior uveitis.

Early on, limited flexibility of the lower spine is noted. Enthesopathy, new bone formation at the attachment of tendons and ligaments, may be noted. Over time, ankylosing spondylitis progresses to involve the entire spine—lordosis (forward curvature) of the lumbar spine, kyphosis (excessive curvature with convexity backward) of the thoracic spine, and hyperextension of the cervical spine. Other joints are involved in about 33% of cases, most frequently presenting with inflammation of the hips, knees, ankles, and shoulders. Osteoporosis is noted in early and late stages of the disease in 19% to 62% of cases and may result in vertebral fractures. Tendons and ligaments can also become inflamed. Cardiac complications include valvular disease (e.g., aortic valve stenosis) and aortitis. Ankylosing spondylitis can affect the bones of the rib cage, reducing lung capacity. Patients may have signs of psoriasis or IBD.

Demographics

Significant History

• Lower back pain in the morning and after inactivity
  
• Stooped posture
  
• Sleeping in a fetal position to minimize pain
  
• Awakening during the second half of the night because of back pain
  
• Recurrent unilateral uveitis

Ancillary Tests

• CBC—may reveal mild anemia
  
• HLA-B27—positive
  
• ESR—may be elevated during active stage
  
• C-reactive protein (CRP)—may be elevated during active stage
  
• Rheumatoid factor—negative
  
• Antinuclear antibodies (ANAs)—negative
  
• Spine and/or pelvis x-ray—look for Romanus lesion—early radiographic sign indicative of disc margin erosion
  
• Technetium bone scan—more sensitive than plain film x-rays
  
• Vitamin D levels—identify patients at risk for osteoporosis
  
• Spine mobility measurements
  
• Electrocardiogram

The Treatment

Exercises to strengthen the back muscles to maintain erect posture, to maintain chest expansion, and to maintain or improve spinal mobility should be part of the patient’s daily routine. Physical therapy is also useful. Heat applied to the joints helps reduce joint pain unless active inflammation is present in which case cold packs are preferred. The patient should be encouraged to sleep on a firm mattress with good neck support. A smoking cessation program, if pertinent, should be a priority. Oral nonsteroidal anti-inflammatory agents are the first line of therapeutic intervention. More aggressive management includes sulfasalazine and other disease-modifying antirheumatic drugs. TNF-α antagonists, such as etanercept, infliximab, and adalimumab, are useful if conventional treatment fails. Intra-articular corticosteroid injections may be beneficial. Topical corticosteroids and cycloplegics are used to manage the anterior uveitis. Approximately 90% of patients remain fully independent with little or no disability.

Behçet’s Disease

Tammy P. Than

ICD-9: 136.1

     THE DISEASE

Pathophysiology

Behçet’s disease is a rare, nongranulomatous, obliterative vasculitis that is thought to be immune mediated. Antiendothelial cell antibodies are detected in an increased prevalence and neutrophils are hyperactive interacting with T cells. Activated T cells produce TNF-α which results in increased levels of proinflammatory cytokines. It affects arteries and veins resulting in thrombosis. The disease is chronic and multisystemic, characterized by oral and genital mucocutaneous ulcerations, skin rashes, arthritis, thrombophlebitis, uveitis, colitis, and neurologic symptoms.

Etiology

The Patient

Clinical Symptoms

Prior to the onset of Behçet’s disease, the patient may experience a prodrome and report malaise, weight loss, anorexia, general weakness, and headache. During the disease process, the patient will complain of a painful mouth and genital sores, photophobia with a red and painful eye, and joint pain.

Clinical Signs

Behçet’s disease waxes and wanes with periods of exacerbation and remission. As time passes, the recurrence frequency decreases and the severity diminishes.

Ocular signs are present in 75% of patients. Bilateral nongranulomatous uveitis, which may include a small hypopyon, usually follows the onset of oral ulcers by 3 to 4 years, but ocular disease is the initial presentation in 20% of patients. Late-stage ocular complications include neovascularization, glaucoma, cataracts, retinal detachment, vascular occlusive disease, and optic atrophy. Other potential ocular manifestations are sixth-nerve palsy, hemiparesis, visual field loss, idiopathic intracranial hypertension, internuclear ophthalmoplegia, and complications from intracranial artery aneurysms.

The Treatment

There is no established standard therapeutic regimen for Behçet’s disease, but treatment is guided by organ involvement. Prognosis has improved in the past decade with more aggressive treatment strategies.

Allergic Conjunctivitis

Salisa K. Williams and Daniel Ullmann

The ocular surface may present an immunologic response as an inflammation of the conjunctiva and cornea. According to the Gell and Coombs classification system for immunologic reactions, four types of hypersensitivity reactions are recognized:

Type I: Immunoglobulin E (IgE)-mediated. This is also known as immediate hypersensitivity that can manifest as an anaphylactic (systemic) or atopic (local) reaction. The antigen binds to the antigen-binding fragment (Fab) portion of the IgE on either mast cells or basophils. Mast cells produce the initial reaction, while basophils initiate the late phase reaction. The cross-linking causes degranulation and the release of histamine resulting in increased vascular permeability and smooth muscle contraction.

Type II: Antibody-mediated (cytotoxic). Circulating antibodies react with antigens on the surface of cells, which leads to cell damage by either phagocytosis or complement activation. These cytotoxic reactions appear to be the underlying etiology of cicatricial pemphigoid (CP) and Mooren ulcer.

Type III: Immune-complex mediated. Soluble antigen-antibody complexes form when the antigen is abundant. Complex deposition in tissues causes type III hypersensitivity. The Arthus reaction is a classic systemic type III reaction, while Wesley rings are an example of a corneal type III reaction.

Type IV: Cell-mediated (delayed type). Presentation of antigen to CD4+ T cells leads to tissue damage via the release of cytokines and the subsequent accumulation of neutrophils and macrophages. Ocular examples of type IV hypersensitivity include drug allergies, corneal allograft rejection, and contact dermatitis.

This section presents the major hypersensitivity conditions involving the conjunctiva, more commonly referred as allergic conjunctivitis.

Seasonal Allergic Conjunctivitis and Perennial Allergic Conjunctivitis

ICD-9: 477.9

     THE DISEASE

Pathophysiology

Once primary exposure and sensitization to antigens occur, repeat exposure to the antigen initiates the inflammatory response. Mast cells migrate into the conjunctival epithelium and are the primary cell type involved in the inflammatory response. Degranulation of mast cells and basophils releases histamine, bradykinins, and leukotrienes. These primary inflammatory mediators induce vasodilatation, tissue edema, and nerve stimulation.

Etiology

Among patients with allergic conjunctivitis, airborne allergens such as ragweed, pollens, dander, dust, or mold spores initiate the immune response resulting in symptoms of allergic conjunctivitis. Patients with SAC present with symptoms in the spring, summer, and fall due to the abundance of airborne allergens found in tree pollen, grass pollen, and weed pollen, respectively.

Patients with PAC may present symptoms throughout the year; thus, in addition to the seasonal allergens, other allergens such as dust mites, cockroaches, and pet dander play a role in the development of symptoms among these patients.

The Patient

Clinical Symptoms

Patients with SAC and PAC complain of conjunctival hyperemia, burning, tearing, and ocular itching. Symptoms are transient, recurrent, and often follow seasonal patterns. The timing of the symptoms differentiates between patients with SAC and patients with PAC.

Clinical Signs

3. Dermatological Evaluation of eczematous lesions to assess the extent of dermatitis and lichenification on the face, scalp, antecubital and popliteal areas, eyelids, neck, outer canthi, and behind the ear lobes. Consultation with a dermatologist is advisable.

Demographics

The prevalence of AD has been estimated from 10% to 20% in children and from 1% to 3% among adults. It typically develops before 5 years of age (90% of cases) and most often by 1 year of age (60%). There is a family history of AD, asthma, or hay fever in 70% of patients. About 40% of patients experience a spontaneous remission by age 5 years.

Significant History

• Chronic, pruritic, erythematous inflammation of the skin
  
• Asthma
  
• Allergic rhinitis (hay fever)

Ancillary Tests

• Serum IgE level and evaluation of skin test reactivity may aid in confirming the diagnosis.
  
• Culture of the eyes with conjunctivitis associated with AD usually grow out Staphylococcus aureus.

The Treatment

1. Moisturizers, cold compresses, and preventive measures: Treatment should be directed at decreasing xerosis and pruritis with frequent moisturization of the skin with creams (i.e., Eucerin, Cetaphil) or ointments (i.e., white petrolatum jelly or Vaseline). Additionally, cold compresses applied directly to the skin, as needed, decrease itching. Avoidance of sudden changes in temperature or humidity help to decrease symptoms, as does avoidance of sweating or overheating. Scratchy materials (i.e., wool or other irritants) and harsh soaps, detergents, and solvents should also be avoided. Environmental factors that trigger allergies (i.e., pollens, molds, dust mites, and animal dander) should be identified and avoided. For ocular symptoms, artificial tears, instilled four to six times per day, or cold compresses applied to the eyelids may provide relief.

Corneal findings include persistent keratopathy, corneal neovascularization, corneal scarring, and the development of keratoconus. AKC has also been associated with a higher incidence of cortical cataract formation (10% of cases). Patients with AKC have depressed T-cell function and may develop staphylococcal blepharitis, meibomianitis, and herpetic keratitis as secondary complications. Rhegmatogenous retinal detachment (equivalent to traumatic detachment) has been linked to AKC attributed to vitreal degeneration secondary to excessive eye rubbing practice by patients to alleviate symptoms of itching.

Demographics

Patients with AKC range from late teens to 50 years of age, with peak incidence between the ages of 30 and 50. This condition occurs more often in men than in women. Among patients with AD, the prevalence of AKC is from 25% to 40%.

Significant History

• Medical history of atopic disease (dermatitis, asthma, rhinitis)
  
• Medical history of multiple allergies including those to food
  
• Ocular history of symptoms of itching, tearing, ropy discharge, burning, photophobia, and decreased vision

Ancillary Tests

Ancillary tests are generally not useful in diagnosing AKC. Conjunctival biopsy can help differentiate AKC from CP. Conjunctival biopsy results reveal excessive eosinophils, mast cells, and goblet cells. Conjunctival biopsy can also help to histologically differentiate AKC from CP by the presence of basement membrane antibodies or complement components in CP.

The Treatment

1. Symptomatic relief may be obtained with cold compresses, applied to the eyelids for 10 minutes, four to six times daily, and artificial tears instilled four to six times daily. Maintenance of a cool, moist environment is helpful. In the case of a patient with blepharitis or meibomianitis, the application of warm compresses to the eyelids for 10 minutes, four times daily, and eyelid scrubs, twice daily, provide reduction of symptoms.

Clinical Signs

Three forms of VKC are generally recognized, palpebral, limbal, and mixed. In the palpebral form, large papillae (cobblestones) develop on the superior tarsal conjunctiva. The papillae are diffuse and may have flattened tops. In the limbal form, gelatinous nodules form in a thickened limbal conjunctiva. These nodules may have small white dots (Horner-Trantas’ dots), which are accumulations of eosinophils. Many patients may present with signs of both limbal and palpebral forms, and hence patients are classified as having mixed VKC. Prominent mucus discharge is often present and can adhere to the giant papillae. In some cases, the discharge can precede the development of giant papillae. The most common corneal finding is punctate keratitis, which can lead to further epithelial breakdown and the development of corneal ulceration or shield ulcer. Shield ulcers are typically located in the superior one third of the cornea, and they tend to have a horizontally oval shape with sharp borders. Shield ulcers are rarely painful. These ulcers are likely the result of epithelial breakdown from exposure to inflammatory mediators or from direct trauma from the giant papillae. Corneal lesions are found in only 3% of severe forms and up to 50% of palpebral forms of VKC. About 30% of patients who develop corneal involvement will have decreased visual acuity. Patients with VKC also have an increased incidence of keratoconus, pellucid marginal degeneration, and cataracts.

Demographics

VKC is a condition that affects younger patients with peak incidence occurring between the ages of 8 and 12. Younger patients tend to be predominately male; however, this sex predilection may be reduced with increasing age of onset. The majority of affected patients are under the age of 20 years. The average duration of VKC is 4 years. In most patients, this condition is resolved by age 30. The disease is more common in dry, warm climates or in areas with polluted air. In more temperate climates, VKC tends to be seasonal with symptoms increasing in the spring and decreasing in the fall. In the sub-Saharan region of Africa, VKC is a significant global health issue.

Significant History

• Personal or family history of atopy (allergic rhinitis, AD, or asthma)
  
• Medical history of intense itching, lacrimation, foreign body sensation, blepharospasm, and photophobia

Ancillary Tests

VKC remains a clinical diagnosis; therefore, ancillary testing is not done.

The Treatment

1. Supportive ocular treatment: As with AKC, VKC may be treated with the application of cold compresses to the eyelids for 10 minutes, four to six times daily, as well as artificial tears four to six times daily. Maintenance of a cool, moist environment is helpful.

The Patient

Clinical Symptoms

Patients who develop GPC exhibit a predictable set of symptoms. Patients wear the contact lenses without complication for weeks or months, and suddenly symptoms develop. Most cases are bilateral, although unilateral and asymmetric GPC can occur. Patients typically complain of itching, burning, chafing, increased mucus discharge, increased contact lens movement with blinking, decreased contact lens wearing time, and blurring of vision when wearing their contact lenses. In severe cases, patients may complain of eyelid swelling and eyelid drooping. Symptoms generally evanesce when contact lens wear is discontinued.

Clinical Signs

GPC is divided clinically into four stages:

• Stage I. There are no visible changes of the papillae. Upon removal of the contact lens, there may be some minimal mucus and mild itching. Both lens comfort and vision are adequate.
  
• Stage II. During this stage, the papillae are starting to form and enlarge up to 0.5 mm in diameter. There is a moderate amount of mucus and redness of the palpebral conjunctiva. The contact lens will be mildly coated, and wearing comfort is slightly decreased. Visual acuity through the lens remains adequate.
  
• Stage III. At this stage, the papillae may have increased to 0.7 mm in diameter. Mucus strands or globs are present, and the contact lens is moderately to heavily coated with a corresponding markedly decreased lens wearing comfort. Vision acuity is variable.
  
• Stage IV. During this stage, the papillae have a diameter greater than 0.7 mm, and there is a copious amount of mucus discharge resulting in the eyelids sticking together. There is pain on contact lens insertion with excessive movement and often off-center positioning of the lens (high-riding with the lids). Lenses are unwearable, and vision is markedly diminished.

Prominent Signs

• Conjunctival hyperemia
  
• Mucus discharge causes the eyelids to stick together and limits the mobility of the contact lens during blinking and eye movements
  
• Giant papillae (cobblestones) of the upper tarsal conjunctiva
  
• Secondary eyelid edema and ptosis
  
• Scarring of conjunctiva in advanced cases
  
• Contact lens coated with a grayish-white film that makes it look dry and dull

Demographics

Most patients with GPC wear soft contact lenses (47.5%), with rigid gas permeable (RGP) contact lens wearers being less prevalent (21.6%). GPC has been reported with ocular prosthesis, exposed sutures from corneal surgery, exposed buckling material from retinal detachment surgery, eyes with corneal deposits of keratin and calcium, band keratopathy, or filtering bleb. Tear film breakup time, the type of ametropia, and keratometry are not risk factors for the development of GPC.

Significant History

• Contact lens wearer
  
• Improper or poor contact lens hygiene
  
• History of seasonal allergies
  
• Younger age

Diagnosis of GPC is primarily clinical.

The Treatment

Stage 1: Refit with frequent replacement or disposable contact lenses, with replacement intervals of 2 weeks to 3 months. Replace conventional hydrogel contact lenses at least two times per year and institute daily cleaning with hydrogen peroxide and unpreserved saline solution. Enzymatic cleaning one to two times per week if contact lenses are replaced at more than 2-week intervals.

Stage 2: Frequent replacement of daily wear contact lenses, with a replacement cycle of 2 to 4 weeks or daily disposable contact lenses. Change contact lens material, that is, from soft hydroxyethyl methacrylate (HEMA) contact lens to non-HEMA material, with replacement every 4 to 6 months. Daily cleaning with hydrogen peroxide and unpreserved saline solution with initiation of a weekly enzymatic cleaning regimen or other designated solution.

Stage 3: Discontinue contact lens wear for approximately 4 weeks. When apical staining or the appearance of tarsal papillae has resolved, refit with frequent replacement or disposable contact lenses worn on a daily wear basis and replaced every 1 to 2 weeks, with daily cleaning with hydrogen peroxide and unpreserved saline solution. An alternative plan is to refit with RGP (high silicon or coated) contact lenses.

Richard F. Multack, Samuel J. Multack and Leonid Skorin Jr

ICD-9: 714.30

     THE DISEASE

Pathophysiology

Juvenile rheumatoid arthritis (JRA), also known as juvenile idiopathic arthritis (JIA), is an autoimmune disease that results in inflammation of the synovia, an oily fluid that lubricates the joints. It is the most common systemic disease associated with iridocyclitis in the pediatric age group. Risk factors for developing uveitis include a positive antinuclear antibody (ANA), being female, and pauciarticular onset. Uveitis will generally develop within 5 years of the onset of the joint disease. The eye may be white with or without pain. The uveitis is often bilateral. Analysis will often reveal a positive ANA, negative rheumatoid factor (RF), and an elevated erythrocyte sedimentation rate (ESR). Based on the mode of onset of the disease and the extent of joint involvement during the first 6 weeks, the following three subgroups of JRA/JIA are recognized:

1. The monoarticular or pauciarticular subgroup involves four or fewer joints and constitutes 40% to 60% of cases. Type 1 is seen in girls less than 5 years of age who have up to a 25% chance of developing chronic iridocyclitis. Type 2 is seen in older boys and has a high association with HLA-B27. These patients are likely to develop acute recurrent iridocyclitis. This subgroup has a relatively high risk of developing uveitis.

2. The polyarticular subgroup affects five or more joints at onset and constitutes 20% to 40% of cases. This subgroup has a moderate risk of developing uveitis (7% to 14%).

3. The systemic onset subgroup results in high remittent fever and at least one of the following features: generalized lymphadenopathy, fever of unknown origin, hepatomegaly, splenomegaly, pericarditis, and a transient maculopapular rash, which is most prominent on the trunk and limbs. This subgroup constitutes 10% to 20% of cases. The risk of developing uveitis in this subgroup is low (<6%).

Etiology

The exact etiology of JRA/JIA is unknown, although various genetic markers have been identified. These include HLA-DR5 and HLA-DPw2. Factors that may contribute are being researched and include infection, a genetic predisposition, an autoimmune response, and hormone interaction.

The Patient

Symptoms and signs, including that of anterior uveitis, depend on which particular subgroup of JRA the patient has. Still’s triad of low-grade uveitis, band keratopathy, and cataracts are found more often in pauciarticular JRA but can be found in any variety. As mentioned earlier, the eye is often white and not inflamed. There may or may not be associated with mild to moderate pain, blurring, or photophobia.

Clinical Symptoms

Clinical Signs

1. Nonocular signs

• Low-grade fever
  
• Swollen and tender joint or joints

2. Ocular signs

• Clinically silent in up to 50% of cases
  
• Nongranulomatous iridocyclitis
  
• Dyscoria from posterior synechia
  
• Band keratopathy
  
• Cataracts—up to 50% of cases
  
• Secondary glaucoma
  
• Keratic precipitates (KPs)—small-medium, rarely mutton fat
  
• Macular edema and macular folds

Demographics

The peak incidence of JRA is between 1 and 4 years of age, but it can appear throughout childhood. The incidence is approximately 113 cases per 100,000 individuals. The ratio of affected females to males is 3:1 with polyarticular involvement, 5:1 in pauciarticular involvement, and equal involvement in the systemic group. The incidence of bilateral ocular involvement varies between 67% and 89%.

Significant History

• Swollen and tender joints
  
• White pupil

Ancillary Tests

Ocular assessment includes visual acuity, pupil testing, slit-lamp evaluation, tonometry, and dilated fundus examination.

A screening slit-lamp examination should be performed every 3 to 4 months in ANA-positive pauciarticular and polyarticular JRA children whose age of onset was under 7 years. Screenings should be performed every 6 months in pauciarticular or polyarticular JRA children who are ANA negative or whose age of onset was over 7 years of age. Children who develop systemic onset JRA should be examined every 12 months. If no uveitis is discovered after 4 years, the ANA-positive children whose onset was less than 7 years of age can be seen every 6 months, and all patients whose onset was after 7 years of age can be seen annually. After 7 years from the time of onset, all patients are considered to be at low risk for developing uveitis and can be seen yearly from that point onward. Laboratory studies: The incidence of a positive ANA ranges from 71% to 93% in JRA patients with uveitis, compared with 30% in those without uveitis.

The RF is usually negative. The ESR, C-reactive protein (CRP), and immune complexes are useful as nonspecific indicators of disease activity.

The knee is the joint most commonly affected, and a routine knee examination and x-ray can be done in cases where JRA is suspected.

The Treatment

Band keratopathy can be removed by scraping or with chelating agents such as disodium EDTA.

Glaucoma is managed as any secondary form of glaucoma. Standard glaucoma surgeries are often unsuccessful. Antifibrotics (5-fluorouracil, mitomycin-C) and aqueous drainage devices are usually required.

In those patients who develop cataracts, lensectomy with vitrectomy and no intraocular lens placement may be indicated. Prior to cataract extraction, the eye should be quiet for 3 months, the anterior chamber angle should be evaluated for synechiae, and adequate anti-inflammation and immunosuppressive therapy should be used perioperatively.

Pars Planitis

Tammy P. Than

ICD-9: 363.21

     THE DISEASE

Pathophysiology

According to the Standardization of Uveitis Nomenclature working group, pars planitis is a chronic inflammation characterized by cells and debris in the vitreous with exudates overlying the peripheral retina, ora serrata, or pars plana ciliaris and occurring in the absence of systemic disease or associated infection. Pars planitis is a more specific clinical entity than intermediate uveitis, which is a broad term used when inflammation is located predominately in the vitreous. Histocompatibility gene typing reveals that HLA-DR15 (suballele of HLA-DR2) is present in 50% to 64% of patients with pars planitis. Increased frequencies of several other HLAs have been noted, including HLA-B8, HLA-B51, HLA-DR17, and HLA-DR2, which suggests an immunogenetic predisposition to pars planitis.

Etiology

The etiology and pathogenesis of pars planitis remain unknown. It may be an autoimmune reaction against the vitreous, peripheral retina, and ciliary body. The differential diagnosis of pars planitis includes intermediate uveitis associated with retinitis pigmentosa, cat scratch disease, Epstein-Barr virus, tuberculosis, Lyme disease, ocular lymphoma, syphilis, and Crohn’s disease. Between 80% and 90% of patients maintain a visual acuity of 20/40 or better in the less involved eye over time.

The Patient

Clinical Symptoms

The symptoms may be so mild that pars planitis may go undetected for several years until young adulthood. The patient may complain of floaters and blurred vision. Pain, photophobia, and ocular redness are usually absent or minimal.

Clinical Signs

The clinical signs, which are bilateral in up to 80% of cases and may wax and wane for 15 to 30 years, include

• Anterior vitreous cells
  
• Peripheral retinal snowballs (free-floating yellow-white exudates)
  
• Snowbanks (layered vitreous exudates over the inferior pars plana and ora serrata)
  
• Variable degree of peripheral retinal periphlebitis
  
• Absent or mild anterior chamber reaction

Demographics

Pars planitis is a disease of children and young adults that has a bimodal age distribution with peaks at 5 to 15 years and also at 20 to 40 years. The disease rarely presents after age 40. There appears to be a slight predilection for males in the younger group and slightly more females in the older group. The average age of diagnosis is 26 years. Pars planitis accounts for up to 15% of uveitis cases in adults. Prevalence in children is higher, accounting for up to 27% of cases with uveitis.

Significant History

• Insidious onset and may be asymptomatic for several years during childhood
  
• Increased floaters in younger patient
  
• Blurred vision in younger patient

Ancillary Tests

Ocular examination requires careful evaluation of the anterior chamber. A significant anterior chamber reaction may be indicative of a panuveitis. A dilated fundus evaluation utilizing binocular indirect ophthalmoscopy with scleral indentation is necessary to visualize snowballs and snowbanks. Fluorescein angiography and optical coherence tomography (OCT) are useful in detecting subtle macular edema and aid in the diagnosis of neovascularization. Although pars planitis is idiopathic, intermediate uveitis is often associated with other diseases; therefore, laboratory testing may include

• CBC with differential
  
• Syphilis serology (FTA-ABS and RPR)
  
• Purified protein derivative (PPD)
  
• Chest radiograph to rule out sarcoidosis and tuberculosis
  
• Angiotensin-converting enzyme (ACE)
  
• Lyme titers
  
• Magnetic resonance imaging (MRI) in patients older than 25 (if other findings and history are suggestive of multiple sclerosis)

The Treatment

Usually, no treatment is administered if acuity is good (20/40 or better). However, because of numerous complications, early aggressive treatment is advocated by some if any amount of macular edema is present.

Reactive Arthritis

Tammy P. Than

ICD-9: 099.3—REITER’S DISEASE (SYNDROME)

ICD-9: 372.33—CONJUNCTIVITIS IN MUCOCUTANEOUS DISEASE

     THE DISEASE

Pathophysiology

The pathophysiology is uncertain but is thought to be an interaction between bacterial antigens, inflammatory components, and the immune system, combined with a genetic predisposition (HLA-B27). Reactive arthritis is a seronegative spondyloarthropathy encompassing an entire spectrum of disease. Reiter’s syndrome traditionally refers to the classic triad of arthritis, conjunctivitis, and urethritis. A fourth manifestation, mucocutaneous lesions, occurs at high frequency.

Etiology

Reactive arthritis usually begins after an infection of the genitourinary or gastrointestinal tract. The major enteric bacteria are Shigella, Salmonella, Campylobacter, and Yersinia, while the most common venereal infection is Chlamydia trachomatis. The predisposing antigen, HLA-B27, is present in 75% to 90% of cases.

The Patient

Clinical Symptoms

The patient will complain of joint stiffness, heel pain, genitourinary discharge, and skin lesions. Ocular complaints will include mucopurulent discharge, discomfort, red eye, and possibly photophobia.

Clinical Signs

Ocular signs occur in 50% of postvenereal cases and 75% of cases following an enteric infection. Bilateral conjunctivitis is most common and may be observed before or at the onset of arthritis. The second most common ocular finding is acute, nongranulomatous, unilateral anterior uveitis. Ocular complications include cystoid macular edema (CME), epiretinal membrane, optic nerve edema, glaucoma, and cataracts.

Systemic signs include asymmetric arthralgia of the knee, ankle, and toes; sacroiliitis; enthesitis (painful inflammation of tendon or ligament attachment to bone); and talagia (heel pain). The peripheral arthritis is usually acute and migratory. Mucocutaneous lesions are present in 80% of cases and include keratoderma blennorrhagicum (scaling lesions of palms and soles), circinate balanitis (genital ulcers), and painless oral ulcers. Reactive arthritis may also be associated with nail abnormalities (onycholysis, subungual hyperkeratosis), amyloidosis, aortitis, pulmonary fibrosis, prostatitis, and pulmonary fibrosis.

Fewer than 50% of patients present with the complete triad (arthritis, urethritis, and conjunctivitis).

Demographics

Significant History

• History of gastrointestinal disease
  
• History of genitourinary infection

Ancillary Tests

Ocular evaluation includes a thorough slit-lamp examination of the conjunctiva, cornea, and anterior chamber. A dilated fundus examination is needed to rule out posterior segment complications.

There is no diagnostic test for reactive arthritis, but the following laboratory tests are useful:

• CBC with differential (leukocytosis is common; mild anemia may be present)
  
• ESR—may be elevated during active stage
  
• CRP—may be elevated during active stage
  
• HLA-B27
  
• Rheumatoid factor—negative
  
• ANA—negative
  
• Microimmunofluoresence for C. trachomatis
  
• Creatinine—elevated
  
• Radiologic studies corresponding to patients’ arthralgias

The Treatment

Reactive arthritis is often not self-limiting and is recurrent and chronic. Antibiotic treatment has not proven effective in shortening the ocular manifestations. The anterior uveitis should be treated with topical corticosteroids and cycloplegics. If reactive arthritis is secondary to Chlamydial infection, oral azithromycin 1,000 mg for 1 day should be prescribed. The patient’s sexual partners should also be treated. The arthralgia is managed with oral nonsteroidal anti-inflammatories, corticosteroids, or immunosuppressive agents. TNF-α antagonists, such as infliximab, may be beneficial in refractory cases. Enthesitis responds to local corticosteroid injections. The mucocutaneous lesions respond to corticosteroids, phototherapy, and methotrexate. Physical therapy is also useful.

Tuberculosis

Langis Michaud

ICD-9: 017.3

After years of decline, tuberculosis has re-emerged as an important systemic and ocular disease. Being primarily a pulmonary illness, clinical manifestations could also be seen in the eye, brain, intestines, kidneys, and bones.

     THE DISEASE

Pathophysiology

Tuberculosis is caused by Mycobacterium tuberculosis, an obligate aerobe that develops in an environment with high oxygen tension, such as the lung apices or in the choroid of the eye. Humans are its only known natural host and the disease is transmitted through direct contact from person to person. Healthy individuals can, once infected, develop a chronic and indolent systemic illness, affecting all tissues or organs of the body. Tuberculosis manifestations vary according to the immune status of the host and the strain of the organism.

Etiology

Immune reaction to the presence of M. tuberculosis is characterized by a delayed hypersensitivity and an aseptic reaction either to mycobacterial antigens or to the presence of viable mycobacteria invading the tissue, the latter being specifically associated with a TH1 cell–driven granulomatous reaction. Primary ocular tuberculosis occurs when the eye is the initial portal of entry into the body, whereas secondary ocular tuberculosis comes by the spread from an adjacent structure.

The Patient

Ocular Tuberculosis

Most patients with ocular involvement have no history of pulmonary or other systemic forms of tuberculosis. The most common site of infection is the choroid; but, the disease can affect any other ocular structure including the orbit.

Clinical Symptoms