AUTHOR AND EDITOR INFORMATION

Section 1 of 10  

• Authors and Editors
• Classification Systems
• Classification Parameters
• Patient Demographics
• Localization of the Inflammatory Process
• Character of the Inflammatory Process
• Etiology of the Inflammatory Process
• Classification
• Practical Diagnostic Approach to Uveitis Outline
• References

CLASSIFICATION SYSTEMS

Section 2 of 10  

• Authors and Editors
• Classification Systems
• Classification Parameters
• Patient Demographics
• Localization of the Inflammatory Process
• Character of the Inflammatory Process
• Etiology of the Inflammatory Process
• Classification
• Practical Diagnostic Approach to Uveitis Outline
• References

Uveitis may be caused by a myriad of conditions, all causing inflammation of the uveal tract (ie, iris, ciliary body, choroid) or adjacent ocular structures (eg, retina, optic nerve, vitreous, sclera). The differential diagnosis is extensive, and the epidemiology changes with the emergence of new uveitic entities. Various genetic, ethnic, demographic, and environmental factors influence the patterns.

Classification and standardization of uveitis is important, as it enhances the precision and comparability of clinical research from different centers and assists in the development of a complete picture of the course of the disorders and their response to treatment. Attempts have been made to standardize some aspects of uveitis, and various classification criteria, inflammation grading schema, and outcomes criteria have been described.

Uveitis may be classified in a number of ways, according to several systems and multiple descriptors. Mastering one, solid, replicable process to best evaluate, diagnose, and treat patients with intraocular inflammation is essential for the astute clinician dealing with ocular inflammation.

The most widely used classification of uveitis was devised by the International Uveitis Study Group (IUSG) in 1987 based on the anatomical location of the inflammation.

In 2005, the Standardization of Uveitis Nomenclature (SUN) Working Group devised additional classification criteria for uveitis. The consensus by the group members was that an anatomical classification of uveitis should be used and that this classification should serve as a framework for subsequent work on diagnostic criteria for specific uveitic diagnoses. A standardized grading schema for anterior chamber cells, anterior chamber flare, and vitreous haze was developed. Outcomes and results reporting were also standardized.

CLASSIFICATION PARAMETERS

Section 3 of 10  

• Authors and Editors
• Classification Systems
• Classification Parameters
• Patient Demographics
• Localization of the Inflammatory Process
• Character of the Inflammatory Process
• Etiology of the Inflammatory Process
• Classification
• Practical Diagnostic Approach to Uveitis Outline
• References

Uveitis may be classified according to numerous parameters, to include the following:

1. Patient demographics
2. Location of the inflammatory process
3. Duration, onset, and course of inflammation
4. Character of the inflammation, including the nature of the inflammatory cells and deposits, distribution of lesions, and the presence of nodules, fibrin, or synechiae
5. Etiology of the inflammation

The intellectual exercise of naming each parameter allows the clinician to focus upon those diagnoses most likely attributed to each patient's disease. Thus, a specifically tailored, cost-effective uveitis evaluation may be obtained to further process the differential for a given constellation of parameters.

Appropriate office setting and clinical laboratory tests are essential to the proper diagnosis of uveitis. However, the application of such resources should not be either difficult or financially burdensome for the clinician and should be justly focused for the patient.

This article is designed to provide the clinician with a direct approach for the evaluation of uveitis leading to current therapeutic modalities in the treatment of uveitis. For excellent patient education resources, visit eMedicine's Eye and Vision Center. Also, see eMedicine's patient education articles Anatomy of the Eye and Iritis.

The steps involved in the workup of a patient include naming, meshing, office testing, specific and nonspecific laboratory tests, specialty consultations, therapeutic tests, and diagnosis and treatment. Through this type of disciplined, practical, and economically sound approach to patient classification and evaluation, the ophthalmologist best serves the patient.

Naming

As with every patient, the initial source for determining the etiology of a patient's complaint involves an accurate history and a physical evaluation. The history and the physical evaluation must be properly organized to judiciously proceed to a differential diagnosis. Additionally, the history and the physical evaluation should be well organized using medical terminology for potential further discussion with other nonophthalmologist physicians as well as other ophthalmologists.

The naming process creates a profile or template of the clinical case. All of the terms describing the salient historical and clinical facts referable to the case under study should be combined in a detailed clinical description of the patient. A listing of uveitis classifications is included in Classification.

Naming example: Mrs. Jackson is a 32-year-old white schoolteacher from Virginia with a history of chronic bilateral diffuse granulomatous uveitis, headaches, hearing loss, and vitiligo. She has no known history of ocular trauma.

Naming breakdown: Patient identifier, age, race, occupation, duration, character of the inflammation, location of the inflammation, and symptoms.

Meshing

Meshing is the process of matching up the findings in the case in question with the findings that characterize a particular entity. Generally speaking, uveitis syndromes are distinct entities. The list of likely uveitic entities is surprisingly small and covers 90% or more of uveitis cases seen in the general practice of ophthalmology.

By comparing patient parameters to established uveitic entities, similar profiles should be included in the preliminary differential diagnosis and then should be ranked in order of likelihood. Based on the previous clinical example, meshing would provide the following differential diagnoses: (1) Vogt-Koyanagi-Harada syndrome (VKH), (2) sarcoidosis, (3) Behcet syndrome, and (4) sympathetic ophthalmia.

Office testing

Many diagnostic tests and procedures can be performed while the patient is in the clinician's office, often during the initial consultation visit.

Specific and nonspecific laboratory tests

Working with the small list of diagnostic possibilities generated by the naming-meshing process, laboratory tests can be ordered to systematically evaluate each possible diagnosis. Some tests arrive in the physician's office the next day, while other tests may require up to a week. Serologic testing for unusual infections may be sent to state health departments or specialty university laboratories for analysis. Histocompatibility antigens often may be drawn only early in the week because lymphocytes must be processed in culture over several days to identify surface antigens.

Specialty consultations

The assistance of colleagues in other specialties is essential to excellence and standardization of medical care. Particularly useful collaborations include those with specialists in internal medicine, pediatrics, infectious diseases, oncology, rheumatology, radiology, nuclear medicine, dentistry, neurology, and dermatology.

Therapeutic tests

Many times, a diagnosis can be firmly established only if the patient actually responds to specific medical therapy, usually an antibiotic. The most significant uveitic diseases responding to antimicrobial therapy include toxoplasmosis, lues, Lyme disease, leptospirosis, tuberculosis, coccidioidomycosis, cryptococcosis, and, of course, infectious postoperative endophthalmitis. Many patients with toxocariasis, on the other hand, will worsen when given antihelminthic drugs and instead will fare better with only anti-inflammatory treatment.

Diagnosis and treatment

The final goal of uveitic classification is a diagnosis, which, in turn, provides either specific therapeutic treatment or appropriate palliative anti-inflammatory therapy.

By using the naming-meshing system and supplementing it with laboratory tests and consultations, 75-85% of patients with uveitis seen in general clinical practice can be correctly diagnosed. In the remaining cases, rarities and masquerade syndromes should be considered, and, if resistance to appropriate therapy continues, the patient should be referred to a uveitis center.

The various parameters required in proper naming and classification of uveitis cases are described below.

PATIENT DEMOGRAPHICS

Section 4 of 10  

• Authors and Editors
• Classification Systems
• Classification Parameters
• Patient Demographics
• Localization of the Inflammatory Process
• Character of the Inflammatory Process
• Etiology of the Inflammatory Process
• Classification
• Practical Diagnostic Approach to Uveitis Outline
• References

Demographic information provides essential data in formulating a differential diagnosis. Age, sex, sexual orientation, race, geographic location, travel history, social habits, and occupation all contribute to the diagnostic synthesis. Therefore, a thorough and comprehensive history is the most important component of the uveitis workup.

Age

The age of the patient often is helpful in focusing the differential diagnosis. Juvenile idiopathic arthritis (JIA), retinoblastoma, and toxocariasis arise predominantly in children. Fuchs heterochromic iridocyclitis, multiple sclerosis, Behcet syndrome, acute posterior multifocal placoid pigment epitheliopathy (APMPPE), and pars planitis occur most frequently in young adults. Reiter syndrome, ankylosing spondylitis, birdshot retinochoroidopathy, and VKH syndrome usually occur in middle-aged patients. Tuberculous and luetic uveitis may present at any age. Elderly patients rarely present with primary uveitis.

Sex

The sex of the patient may provide useful information. Uveitis associated with ankylosing spondylitis, Behcet syndrome, and Reiter syndrome is more common in males, while uveitis associated with JIA more frequently occurs in females. Fungal endophthalmitis and sympathetic ophthalmia are more common in males due to either injury or intravenous drug use. However, most uveitic syndromes have no particular sexual or racial predilection.

Race

The race of the patient may focus the differential even further. For example, human leukocyte antigen B27 (HLA-B27)–associated arthritides are more common in whites and include ankylosing spondylitis, psoriatic arthritis, and Reiter syndrome. Sarcoidosis most commonly presents in blacks. VKH is seen mostly in patients of Asian and American Indian descent. Behcet syndrome is a disease of the ancient Eurasian silk route, from China to Turkey. However, most uveitic syndromes have no particular sexual or racial predilection.

Sexual habits

Sexual orientation may play a role in diagnosis because young, sexually active males are more likely to contract HIV and other AIDS-related infections, such as cytomegalovirus (CMV) retinitis, Kaposi sarcoma, or herpes zoster ophthalmicus. Sexually active individuals are also at increased risk of contracting a sexually transmitted disease, such as syphilis or gonorrhea, which may cause a primary uveitis, or chlamydia, which itself may trigger a HLA-B27-related uveitis.

Geographic history

When suspecting infectious etiologies of uveitis, it is wise to adequately address the geographic location and recent travel of the patient. The endemic nature of histoplasmosis within the Mississippi-Ohio-Missouri River valleys should make the ophthalmologist suspicious of this illness in patients from that area. Histoplasmosis also is relatively localized to the 45° north and 45° south latitudes worldwide. Histoplasmosis is not endemic to Australia, New Zealand, Europe, England, or Japan. Coccidioidomycosis is found predominantly in the southwest United States.

Family history

Family history is important, as some diseases have a genetic predisposition or there may be a greater likelihood that a particular disease will develop by direct transmission from a family member. Inflammatory diseases, such as ankylosing spondylitis, Reiter syndrome, and inflammatory bowel disease, develop in families with HLA-B27. Ocular toxoplasmosis is usually a late result of congenital transmission. A history of infectious diseases (eg, tuberculosis) in a family is helpful when such an entity is suspected.

Social habits

A history of ingestion of raw or undercooked meat is important in arousing suspicion for ocular toxoplasmosis. Contact with feline feces containing oocytes of Toxoplasma gondii may occur in the handling of cat litter or by playing in sand boxes. If ocular toxocariasis is suspected, a history of contact with unwormed cats or dogs is important

Contagious disease exposure

Leptospirosis infection has an increased incidence in sewer workers and those with exposure to rodent urine. Other cases include a history of exposure to contaminated water. A history of exposure to a patient with active tuberculosis may assist in the diagnosis when tuberculosis is being considered as a possible cause of uveitis.

When sexually transmitted diseases, such as syphilis, AIDS, and Reiter syndrome, are being considered, a directed sexual history, including inquiring about previous sexually transmitted diseases, genitourinary symptoms, and sexual practices, may obviate an expensive diagnostic workup. Additionally, a history of intravenous drug abuse may be useful in arriving at a smaller differential diagnosis.

Travel history

Travel and immigration are important components of the uveitis history. Past exposure to tuberculosis or dysentery may be directly related to a recent or recurrent ocular inflammatory episode. Exposure to malaria, yellow fever, typhoid fever, hepatitis A, B, and C, as well as trachoma, leprosy, or onchocerciasis must be considered in rare cases. The local immigration and health departments may provide critical information regarding endemic diseases in specific travel and immigration destinations.

Occupational exposure

Occupational and hobby exposure may provide useful clues to the determined diagnostician, particularly in the farming or animal husbandry environment. Brucellosis may occur in livestock workers and slaughterhouse workers, while some cases of brucellosis are caused by consumption of unpasteurized milk products. Leptospirosis previously was seen in miners or sewer workers; however, most cases today follow exposure to water contaminated by domestic animals carrying the bacteria. Chlamydia psittaci infection results from parrot exposure. Cat scratch disease caused by Bartonella henselae infection and toxoplasmosis can follow feline exposure.

LOCALIZATION OF THE INFLAMMATORY PROCESS

Section 5 of 10  

• Authors and Editors
• Classification Systems
• Classification Parameters
• Patient Demographics
• Localization of the Inflammatory Process
• Character of the Inflammatory Process
• Etiology of the Inflammatory Process
• Classification
• Practical Diagnostic Approach to Uveitis Outline
• References

The anatomical location of the inflammatory process is one of the most important clues to pathogenesis and treatment.

Anterior uveitis

Anterior uveitis comprises inflammation, primarily affecting the anterior segment, and includes iritis, iridocyclitis, and anterior cyclitis. It is the most common form of intraocular inflammation. In a general or comprehensive ophthalmology practice, most patients presenting do not have an underlying systemic disease. Instead, usually at least 50% of the patients presenting with inflammation have predominantly anterior disease caused by either trauma or, most commonly, an idiopathic postviral syndrome. Most physicians and authors do not perform a thorough systemic diagnostic evaluation in patients with first episode mild-to-moderate anterior segment inflammation in the absence of systemic disease or complaints. The directed uveitis history is key in this situation.

Uveitic syndromes associated with primarily anterior segment involvement include HLA-B27 syndromes, herpes simplex and herpes zoster disease, Fuchs heterochromic iridocyclitis, and many arthritic syndromes. Secondary iatrogenic disease often is seen postoperatively, particularly following complications of surgery, trauma, scleral or seton implants, corneal transplants, capsular disruption, or fixed haptic and iris fixated intraocular lens implantation.

Intermediate uveitis

Middle uveitis, cyclitis, intermediate uveitis, pars planitis, peripheral uveitis, or chronic cyclitis often indicates a more severe form of ocular inflammation than isolated anterior disease. According to the SUN classification system, the term intermediate uveitis is used when the primary site of inflammation is in the middle portion of the globe and includes posterior cyclitis, hyalitis, choroiditis, and chorioretinitis. Pars planitis should be used only for that subset of intermediate uveitis where there is snowbank or snowball formation occurring in the absence of an associated infection or systemic disease (ie, idiopathic).

If there is an associated infection (eg, Lyme disease) or systemic disease (eg, sarcoidosis), then the term intermediate uveitis should be used. Sometimes, spillover uveitis (middle inflammation or anterior vitreous cells) may occur, indicating that the primary source of disease is anterior. Intermediate uveitis or cyclitis is commonly associated with major granulomatous diseases (eg, tuberculosis, sarcoidosis, Lyme disease, lues).

Posterior uveitis

Posterior uveitis is inflammation of the choroid and the retina and includes retinochoroiditis, retinitis, and neuroretinitis. Spillover into the adjacent choroid, creating a retinochoroiditis or a chorioretinitis, may occur. Retinitis typically manifests by toxoplasmic or herpetic infection. Choroiditis may occur with any of the granulomatous uveitides (eg, tuberculosis, sarcoidosis, Lyme disease, lues), histoplasmosis, or more unusual syndromes, such as birdshot or serpiginous chorioretinitis. Papillitis may occur with toxoplasmosis, viral retinitis, lymphoma, or sarcoidosis.

Panuveitis

The term panuveitis is reserved for those situations in which there is no predominant site of inflammation, but inflammation is observed in the anterior chamber, vitreous, and retina and/or choroid (ie, retinitis, choroiditis, retinal vasculitis). Diffuse uveitis, panuveitis, or endophthalmitis generally occur with overwhelming infections, such as infantile toxocariasis, postoperative bacterial endophthalmitis, or severe toxoplasmosis. Many of the granulomatous uveitides may produce a highly disseminated pattern, especially when delayed diagnosis occurs.

CHARACTER OF THE INFLAMMATORY PROCESS

Section 6 of 10  

• Authors and Editors
• Classification Systems
• Classification Parameters
• Patient Demographics
• Localization of the Inflammatory Process
• Character of the Inflammatory Process
• Etiology of the Inflammatory Process
• Classification
• Practical Diagnostic Approach to Uveitis Outline
• References

The character of an ocular inflammatory disease can be described in terms of the pathology observed, distribution of lesions documented, location and character of keratic precipitates (KP) in the anterior chamber, presence or absence of synechiae, nodules, or fibrin, and presence of known identifier systemic correlates.

Pathology

Traditional terms have used the granulomatous and nongranulomatous monikers to describe the general character of intraocular inflammation. The term granulomatous is reserved for large, globular, mutton-fat KP, Busacca (iris stroma) and Koeppe (iris margin) nodules, choroidal granulomata, and other indicators of pronounced severe inflammation.

Histopathologic correlates have been established in the literature. The classic granulomatous uveitides (eg, tuberculosis, sarcoidosis, Lyme disease, lues) often are manifested by a classic granulomatous inflammation pattern. Many other uveitides exist that also produce granulomatous inflammation. Nongranulomatous inflammation generally describes a more benign intraocular appearance with smaller KP, less likelihood of synechiae formation, and fewer nodules.

Chorioretinal lesion distribution

Retinal lesions may have several distribution patterns, which may provide invaluable diagnostic clues. There may be a single lesion (focal), several lesions (multifocal), many scattered lesions (disseminated), or diffuse lesions. Diffuse lesions may be seen in lues, sarcoidosis, birdshot retinochoroidopathy, or VKH. Focal lesions are more characteristic of toxoplasmosis. Diffuse inflammation is seen in vasculitic or ischemic disease, and sectorial retinitis may identify herpetic infection in acute retinal necrosis (ARN) or CMV retinitis. Peripheral retinitis may be seen in pars planitis, multiple sclerosis, sarcoidosis, punctate outer toxoplasmosis, or ARN.

Anterior chamber cells and flare

In acute anterior uveitis, the aqueous contains many cells and severe flare. In chronic cases, although the number of cells is considerably smaller, flare may be conspicuous. This is because of the structural alteration in the blood vessels due to long-term inflammation that leads to leaking of proteinaceous fluid and persistent flare. The grading schema for intraocular inflammation typically uses an ordinal scale ranging from 0 to 4+. The SUN Working Group standardized the grading of anterior chamber cells and flare to achieve better compatibility between data from different groups and different studies.

Keratic precipitates

KPs come in several varieties. Mutton-fat KPs occur in granulomatous inflammatory diseases, and they generally fill the Arlt triangle inferiorly. Arlt distribution is caused by convection currents within the anterior chamber and the cooler temperature in the inferior cornea. These larger granulomatous KPs will pigment and then shrink as inflammation abates or is controlled by steroid therapy. They often fail to disappear completely, and they may alter the endothelium where they rest, leaving a halo on the endothelium. Granulomatous deposits also may be seen in the anterior chamber angle by gonioscopy.

Nongranulomatous KPs are small to medium in size and are white in color with an Arlt distribution pattern. Old KPs accumulate pigment, and, as they begin to involute, shrink and disappear.

Either type of KP may be seen within the distribution of a central or peripheral herpetic disciform keratitis, which is often also accompanied by herpetic uveitis. Although the intraocular pressure is, as a rule, lowered in acute anterior uveitis, some patients may have elevated intraocular pressure because of inflammatory debris in the trabecular meshwork or herpetic trabeculitis. Precipitates identical in histopathologic content to KPs also may be seen deposited within the chamber angle, intraocular lenses, or seton implants.

Stellate KPs are unique, fibrillar, dendriform, microscopic lesions found throughout the endothelium. No predilection exists for the center, periphery, or Arlt inferior triangle. Stellate KP typically is seen in Fuchs heterochromic iridocyclitis, but they commonly are noted in herpes simplex, herpes zoster, and CMV retinitis infections. Stellate KPs can be seen in toxoplasmosis, but granulomatous or nongranulomatous KPs also are seen.

Peripheral KPs may be seen following intraocular surgery, with peripheral corneal edema following intracapsular cataract surgery (Brown syndrome), with herpes simplex or zoster uveitis, following acute angle-closure glaucoma, or after blunt ocular trauma.

KPs must be differentiated from corneal endothelial guttatae and pigment deposits. Pigment may have a random, diffuse, central, or disciform distribution following previous inflammation. Krukenberg spindles are found in a central vertical pattern, which is not characteristic of inflammation. Guttatae are central or diffuse and do not fulfill the usual distribution patterns of inflammatory disease. Guttatae can be identified by specular microscopy and more elegantly by confocal microscopy.

Synechiae

Posterior synechiae typically form during acute inflammatory episodes at the location of Koeppe nodules. Both granulomatous and nongranulomatous cases may develop posterior synechiae quite rapidly, but they do not appear in pars planitis. Patients with both intermediate cyclitis and posterior synechiae should be evaluated aggressively for an etiology distinct from pars planitis syndrome. Chronic anterior uveitis also frequently develops posterior synechiae, with or without gross papillary distortion.

Anterior synechiae occur in the angle during chronic or acute inflammation. They may develop during low-grade chronic inflammation with only flare seen in the anterior chamber without cells noted. Significant anterior synechiae in the presence of a functioning ciliary body and compromised trabecular outflow may create severe angle-closure glaucoma despite a deep anterior chamber. Anterior synechiae more commonly are found in deeply pigmented eyes, granulomatous diseases, and traumatized eyes.

Fibrin

Fibrinous exudates occur when overwhelming inflammation produces significant breakdown of the blood aqueous barrier and subsequent massive protein leakage. Fibrinous exudates most characteristically are seen in HLA-B27 disease, as well as severe granulomatous uveitis, postoperative endophthalmitis, trauma, and disseminated infections (eg, fungal endophthalmitis following intravenous drug abuse). Fibrin may form a retracting clot once resolution or aggressive therapy has been instituted.

Nodules

Koeppe nodules occur on the iris sphincter margin and commonly are seen in Fuchs heterochromic iridocyclitis without synechiae formation. Koeppe nodules can be seen in HLA-B27 disease, herpetic infections, and any granulomatous uveitis. Busacca nodules generally are accompanied by even more severe inflammation; therefore, they are less common than Koeppe nodules. These are seen with granulomatous uveitis and never with nongranulomatous uveitis; hence, they are valuable diagnostically.

Duration

The terms acute and chronic have been used inconsistently in the literature and have been used variably to refer to the onset of the uveitis, the duration of an attack of uveitis, or the course of uveitis.

The SUN Working Group standardized these terminologies. The onset of uveitis should be described as either sudden or insidious. The duration of an attack of uveitis should be described as either limited, if 3 months or less in duration, or persistent, if greater than 3 months in duration.

The term acute is used to describe the course of specific uveitic syndromes characterized by sudden onset and limited duration, such as HLA-B27–associated acute anterior uveitis. The term chronic is used to describe persistent uveitis characterized by prompt relapse ( <3 mo) after discontinuation of therapy (eg, chronic uveitis of Fuchs heterochromic cyclitis, JIA–associated uveitis, tuberculous uveitis). The term recurrent should be used to describe repeated episodes of uveitis separated by periods of inactivity without treatment.

Systemic correlates

The basic history for a patient with uveitis is quite simple and includes questions regarding demographics outlined in Classification and a focused pertinent review of systems. This review includes arthritis (hands, fingers, heels, toes, lower back, spine, weightbearing joints), rashes, GI disease (dysentery, colitis, gastritis), oral lesions, genital lesions, sexually transmitted disease, headache, neurologic symptoms, and pulmonary disease.

These specific questions contribute to the ophthalmologist's understanding of each patient presentation. The eye care professional maintains a uniquely advantageous position to provide the most focused cost-effective evaluation of the patient with uveitis.

Many times physicians are frustrated when a new patient with intraocular inflammation is referred back to their internist for workup, only to find that numerous, expensive, nonspecific, unnecessary screening tests were ordered.

Herpes titers are rarely helpful. Toxoplasmosis titers are useful only in the presence of at least somewhat typical retinitis scars. Angiotensin-converting enzyme (ACE) test results are often negative in sarcoidosis cases limited to the eye. Lysozyme is difficult at best to interpret. Lyme disease testing is not applicable to patients who have not been to endemic areas. Fungal titers are rarely applicable, unless typical posterior segment findings are suggestive. Screening sacroiliac films are insensitive in the absence of typical pelvic symptoms. On the other hand, an order for luetic serology in any patient is impossible to criticize.

Remember that many cases of mild, first episode unilateral uveitis may be associated with either trauma or an idiopathic viral or sinus infection. Since these cases present little risk of complications and recurrence, these patients are best served by symptomatic treatment, observation, and no initial diagnostic testing.

ETIOLOGY OF THE INFLAMMATORY PROCESS

Section 7 of 10  

• Authors and Editors
• Classification Systems
• Classification Parameters
• Patient Demographics
• Localization of the Inflammatory Process
• Character of the Inflammatory Process
• Etiology of the Inflammatory Process
• Classification
• Practical Diagnostic Approach to Uveitis Outline
• References

When diagnostic testing has been performed, the specific etiology of the underlying process may be identified. Sometimes, only the category, but not the actual cause of inflammation may be known. This knowledge alone may be sufficient to initiate appropriate therapy. For instance, when history rules out trauma, age rules out ischemia, and comprehensive serologies rule out infection in the presence of arthritis, systemic anti-inflammatory therapy may begin despite the absence of a specific diagnostic syndrome.

Etiology provides the ultimate classification system. A useful technique to classify an inflammatory process, or any process within the eye for that matter, uses the 7 "I" system. This system places every source of ocular inflammation into 1 of 7 categories, with an eighth case for the process of elimination and frustration when all diagnostic means fail to reveal a specific etiology, as follows:

1. Inflammatory - Primary autoimmune disease
2. Infectious - Due to known ocular and systemic pathogens
3. Infiltrative - Referring to invasive neoplastic processes
4. Injurious - Trauma commonly seen in general offices
5. Iatrogenic - Surgery, inadvertent trauma, or medication
6. Inherited - Metabolic or dystrophic disease
7. Ischemic - Impaired circulation can cause inflammation
8. Idiopathic

A diagnosis of idiopathic uveitis implies not only that a thorough, specific, tailored, cost-effective diagnostic workup was performed, but it also implies that treatable infectious diseases have been acceptably ruled out.

CLASSIFICATION

Section 8 of 10  

• Authors and Editors
• Classification Systems
• Classification Parameters
• Patient Demographics
• Localization of the Inflammatory Process
• Character of the Inflammatory Process
• Etiology of the Inflammatory Process
• Classification
• Practical Diagnostic Approach to Uveitis Outline
• References

Age

Infant

Child

Adolescent

Young adult

Elderly adult

Demographics

Sex

Race

Residence location(s)

Travel

Immigration

Occupation

Hobbies

Nutritional and eating habits

Pets

Other illnesses

Stress events and factors

Personality factors

Social history

Smoking

Alcohol use

Drug abuse

Sexual orientation

Anatomical location

Anterior - Iritis, iridocyclitis, anterior cyclitis

Intermediate - Posterior cyclitis, pars planitis, hyalitis

Posterior - Retinitis, retinochoroiditis, chorioretinitis, choroiditis, papillitis

Panuveitis - Diffuse uveitis, endophthalmitis

Chronology or duration

Acute

Subacute

Chronic

Recurrent

Character

Pathology - Granulomatous, nongranulomatous

Lesions - Focal, multifocal, disseminated, diffuse

KP pattern - Focal, central, disciform, Arlt triangle, stellate or diffuse, peripheral (rare)

Associated findings - Synechiae, fibrin, nodules

PRACTICAL DIAGNOSTIC APPROACH TO UVEITIS OUTLINE

Section 9 of 10  

• Authors and Editors
• Classification Systems
• Classification Parameters
• Patient Demographics
• Localization of the Inflammatory Process
• Character of the Inflammatory Process
• Etiology of the Inflammatory Process
• Classification
• Practical Diagnostic Approach to Uveitis Outline
• References

Naming

Patient identifier based upon a repeatable classification system

Meshing

Formulation of a differential diagnosis ordered by probability

Office testing

• Delayed hypersensitivity skin testing for tuberculosis (purified protein derivative [PPD]), anergy for sarcoidosis (Candida or mumps), and rarely histoplasmosis or coccidioidomycosis
• Behcet skin testing
• Photostress and Amsler grid (macular edema, macular retinitis)
• Fluorescein angiography (macular edema, vasculitis, papillitis, choroiditis, retinitis, posterior scleritis
• Tear function testing - Schirmer and breakup time (Sjögren, sarcoidosis, connective tissue diseases)
• Tear lysozyme or lactoferrin (Sjögren, sarcoidosis)
• Conjunctival biopsy (sarcoidosis)
• Aqueous paracentesis (infection, antibody titer, tumor, lens-induced uveitis, eosinophilia)
• Visual fields (glaucoma, optic atrophy, papillitis)
• Contrast sensitivity, color vision (optic neuritis, papillitis)
• Glare testing (cataract, synechiae, capsular opacification)
• Ultrasonography (posterior scleritis, retinal detachment, vitreitis)
• Electroretinogram (chloroquine toxicity, opaque media, birdshotchoroidoretinopathy, retinitis pigmentosa, nonspecific)
• Electro-oculogram (diabetic retinopathy, siderosis retinae, vitiliginous maculopathy, and shallow retinal pigment epithelial detachments)

Specific clinical laboratory tests

• Bacterial antibody testing (toxocariasis, toxoplasmosis, B henselae, brucellosis)
• Viral antibody testing (herpes simplex virus [HSV], CMV, varicella-zoster virus [VZV], Epstein-Barr virus [EBV], hepatitis, HIV, human T lymphotrophic virus (HTLV)
• Luetic serology - Treponemal tests (fluorescent treponemal antibody absorption [FTA-ABS] test, microhemagglutination-Treponema pallidum [MHA-TP]) and nontreponemal tests (rapid plasma reagin [RPR], Venereal Disease Research Laboratory [VDRL] test)
• Lyme disease testing - Serology and polymerase chain reaction (PCR)
• Leptospirosis serology
• Fungal serology - Blastomycosis, coccidioidomycosis, histoplasmosis serum antibodies
• Connective tissue disease - Rheumatoid factor (RF), antinuclear antibody (ANA), lupus anticoagulant, complement, protein electrophoresis, antineutrophil cytoplasmic antibody (ANCA), and specific antinuclear antibodies (single stranded, double stranded DNA, Smith, ribonucleoprotein)
• Nonspecific inflammation - Erythrocyte sedimentation rate (ESR), C-reactive protein (CRP)
• Feces for parasites (Ascaris, Entamoeba histolytica, Escherichia coli, Endolimax nana, Giardia lamblia)
• Angiotensin-converting enzyme (sarcoidosis)
• Lysozyme (sarcoidosis, tuberculosis)
• Major histocompatibility antigens (HLA-B27 syndromes and HLA-A29 in birdshot chorioretinopathy)
• Standard tests - CBC, differential, clotting factors, chemistry, urinalysis
• Cryoglobulins (myeloma and other myeloproliferative neoplasms, rheumatoid arthritis, Sjögren syndrome, lupus erythematosus, Waldenström macroglobulinemia, hepatitis, CMV infections, infective endocarditis, mononucleosis, leprosy)
• Complement levels, interleukin levels, circulating immune complexes
• Chlamydial complement-fixation test
• AIDS tests (ELISA and Western Blot)

Diagnostic imaging

• Chest x-ray (tuberculosis, sarcoidosis, histoplasmosis, tumor)
• Sacroiliac films (HLA-B27, Reiter, ankylosing spondylitis)
• Orbital films, CT scan, or MRI (tumor, foreign body, thyroid, scleritis)
• Skull films (congenital toxoplasmosis)
• Joint films (rheumatoid, HLA-B27, JIA, lupus, gonorrhea)
• Gallium scan (sarcoidosis)

Specialty consultations

• Internal medicine and pediatrics (general evaluation, medication monitor)
• Oncology (cytotoxic immunosuppressive medication monitor)
• Infectious disease (diagnostic and therapeutic assistance, antibiotic medication monitor)
• Dentistry, periodontology (diagnostic assistance with mucosal lesions)
• Dermatology (diagnostic assistance with cutaneous lesions)
• Rheumatology (diagnostic and therapeutic collaboration)

Therapeutic tests

• Tuberculosis systemic therapy
• Luetic systemic therapy
• Lyme disease systemic therapy
• Toxoplasmosis systemic therapy
• Antiviral systemic therapy
• Corticosteroid therapy (nonspecific)
• Diagnostic lensectomy (phacoanaphylaxis)

Invasive diagnostic testing

• Diagnostic vitrectomy
• Aqueous paracentesis
• Vitreous tap
• Corneal biopsy
• Impression cytology
• Conjunctival biopsy
• Retinal biopsy
• Choroidal biopsy
• Impression cytology

Diagnosis and treatment

With a careful history, a directed physical examination, appropriate use of office diagnostic procedures, a tailored approach to laboratory testing, and selective medical consultations, the ophthalmologist can mesh a collection of useful data to obtain a diagnosis in up to 80% of referral uveitis patients and about 50% of uveitis patients in a comprehensive ophthalmology practice.

The main aim of uveitis treatment is to prevent visual loss, discomfort, and ocular morbidity. Depending upon the severity of the condition, the decision to start treatment is made. The initial treatment of uveitis is nonspecific and consists of mydriatic- cycloplegic agents, corticosteroids, immunomodulatory agents, and NSAIDs. Later, as the result of laboratory investigations, special tests and consultations ensue, and specific treatment may be instituted. However, most cases that require treatment only need nonspecific treatment. Expeditious and specific treatment based on a complete and organized diagnostic evaluation is best for the patient, physician, and economy.

REFERENCES

Section 10 of 10

• Authors and Editors
• Classification Systems
• Classification Parameters
• Patient Demographics
• Localization of the Inflammatory Process
• Character of the Inflammatory Process
• Etiology of the Inflammatory Process
• Classification
• Practical Diagnostic Approach to Uveitis Outline
• References

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• Gritz DC, Wong IG. Incidence and prevalence of uveitis in Northern California; the Northern California Epidemiology of Uveitis Study. Ophthalmology. Mar 2004;111(3):491-500; discussion 500. [Medline].
• Jabs DA, Nussenblatt RB, Rosenbaum JT. Standardization of uveitis nomenclature for reporting clinical data. Results of the First International Workshop. Am J Ophthalmol. Sep 2005;140(3):509-16. [Medline].
• Karcioglu ZA, Brear R. Conjunctival biopsy in sarcoidosis. Am J Ophthalmol. Jan 15 1985;99(1):68-73. [Medline].
• Sheppard JD. Posterior uveitis. Ophthalmol Clin North Am. 1993;6:1.
• Sheppard JD, Garovoy MR. The major histocompatibility complex in ophthalmology. In: Friedlander MH, ed. Duane's Basic Ophthalmologic Science. Vol. 1. 1991.
• Sheppard JD, Nozik RA. Practical diagnostic approach to uveitis. In: Duane JA, Jaeger EW, ed. Duane's Clinical Ophthalmology. Vol. 4. 1989.
• Smith RE, Nozik RA. Uveitis: A Clinical Approach to Diagnosis and Management. 2nd ed. Baltimore: Williams & Wilkins;1988.

Article Last Updated: Feb 14, 2007