BASICS OF UVEITIS

MICAH TCHALE

INTRODUCTIONo Uveitis is one of the leading causes of

blindness, which makes it crucial for practicing optometrists to understand how best to diagnose, differentiate and treat it

o Uveitis was once considered as a single disease entity; however, we now know that uveitis can be caused by;

i. Autoimmune disordersii. Infectionsiii. Malignancyiv. Exposure to toxinsv. Idiopathic in nature

o Approx. 50% of uveitis are due to idiopathic conditions, 20% due to trauma, 20% due to systemic underlying cause eg rheumatoid arthritis or sarcoidosis, and 10% due to localized ocular condition eg herpes zoster or toxoplasmosis

o The sight threatening complications of uveitis;i. Glaucomaii. Damage to the retinaiii. Macular edema

PATIENT EVALUATION

o The key to targeted and efficient patient evaluation is a thorough history, physical examination and review of systems

o When patients present with a non-resolving, painful, red eye, our goal is to determine: What is the extent of the current condition? What ocular structures are affected? What is the underlying cause? How can the condition best be treated &

managed?

o The following steps will help answer those questions:

Acute or chronic?• First step is determine whether the clinical course

is acute or chronic• Acute conditions typically have an abrupt onset

lasting several weeks, while chronic conditions can wax and wane over months or years

What structures are affected?• The next step is to identify the anatomical location

of the inflammation or infection• The anatomical classification of uveitis

(International uveitis study group)i. Anterior uveitis (primary site of inflammation is

the anterior chamber)ii. Intermediate uveitis (primary site is ciliary

body and vitreous)

iii. Posterior uveitis (primary focus of inflammation is the retina and choroid)

iv. Panuveitis (primary site of inflammation involving all anterior and posterior)

• Common signs and symptoms of anterior uveitisi. Rednessii. Photophobiaiii. Pain

• Posterior uveitis presents withi. Floatersii. Visual disturbances

Granulomatous or nongranulomatous• Ocular histopathology is another classification

used to differentiate the condition• Granulomatous inflammation

may present acutely, but more often presents as a chronic condition with large, mutton-fat keratic precipitates (KPs) and inflammatory cells (epitheloid cells and macrophages) in the anterior chamber

Often associated with systemic conditions and autoimmune reaction eg syphilis, Lyme disease, TB or a local reactivation of herpetic viral infection

• Nongranulomatous inflammation Usually involves the anterior segment Has an acute onset accompanied by a cellular reaction

in the AC that represents smaller cell types (lymphocytes)

Are idiopathic or due to HLA-B27 involvement Occurs more frequently than does granulomatous

uveitis, especially in patients with anterior uveitis

Unilateral or bilateral• Laterality can help classify the type of uveitis• Unilateral conditions are more commonly acute

and can be infectious• Bilateral conditions are likely due to chronic,

systemic conditions

What are the symptoms and signs?• Patients with uveitis typically present with abrupt,

dull pain and photosensitivity • Additional signs and symptoms

i. Pain (temple or periorbital region)ii. Redness denser toward the limbus with no

mucopurulent dischargeiii. Blurring of visioniv. Watery discharge or tearing (rare)v. Mild epiphora from the pain response

o There are multiple clinical signs that are important for clinicians to look for to help with the differential diagnosis• Patients may present with a decrease in vision

ranging from mild to severe• Circumlimbal injection of the conjunctiva• In chronic uveitis, cornea edema may be present• Hypopyon may be present, which is highly

suggestive of diseases with HLA-B27, Behçet’s disease or infectious uveitis (rare)

• IOP should be taken into account in the diagnosis Low IOP is due to decreased aqueous production in the

acute phases High IOP is found in viral conditions eg HSV

keratouveitis• Peripheral anterior or posterior synechiae have the

potential to lead to secondary glaucomatous conditions

• Posterior subcapsular cataracts may develop with recurrent episodes due to chronic steroid use

Is there a systemic cause?• Ask the patients about their medical history and

other associated symptoms of their conditions provides invaluable clues to possible diagnoses

• Any time a patient presents with minimal signs and symptoms, bilateral presentation, a granulomatous response and a posterior extension of uveitis in the eye, be sure to consider systemic causes

STANDARDIZED GRADING SCALES FOR UVEITIS standardization of uveitis nomenclature

(SUN) scheme for anterior chamber cells (using 1mm slit beam)

GRADE CELLS IN FIELD

0 <10.5+ 1-51+ 6-152+ 16-253+ 26-504+ 50+

SUN Grading scheme for anterior chamber flare

GRADE DESCRIPTION

0 None

1+ Faint

2+ Moderate (iris/lens details clear)

3+ Marked (iris/lens details hazy)

4+ Intense (fibrin/plastic aqueous)

CAUSES OF UVEITIS AUTOIMMUNE Juvenile idiopathic

arthritis Ankylosing

spondylitis Ulcerative colitis Crohn’s disease Reiter’s syndrome Lens induced

INFECTIONS Syphilis Tuberculosis Herpes zoster Herpes simplex Adenovirus

MALIGNANCY Retinoblastoma Leukemia Lymphoma Malignant melanoma

POSTERIOR Cytomegalovirus Toxoplasmosis AIDS Herpes simplex Herpes zoster Candida

IDIOPATHIC TRAUMATIC

ANTERIOR UVEITISo AU is the presence of cell and flare in the

anterior chambero Also referred to as iritis, iridocyclitis and

anterior cyclitiso AU can be associated with other ocular

inflammatory conditions including scleritis, episcleritis, keratitis, posterior segment diseases, postsurgical inflammation or lens related

o The largest number of anterior uveitis cases is idiopathic (HLA-B27 negative)

o The next common etiology is HLA-B 27 positive

o Be sure to perform a thorough case history and a complete review of systems before diagnosing a patient as idiopathic

o Other associated conditions commonly seen with anterior uveitis include; Juvenile idiopathic arthritis Ulcerative colitis Crohn’s disease Reiter’s syndrome Herpes simplex/zoster virus Syphilis tuberculosis

INTERMEDIATE UVEITISo Defined as intraocular inflammation that

predominantly involves the peripheral retina, pars plana and vitreous

o Aka chronic cyclitis, peripheral uveitis and pars planitis

o Proportion of patients with intermediate uveitis is estimated to be 4% to 8% of uveitis cases

Causes of intermediate uveitis include; 69% of unknown etiology 22% due to sarcoid 1% due to multiple sclerosis and Lyme disease

o Helpful questions include asking patients about difficulty in breathing or symptoms of eye pain, neurological symptoms consistent with multiple sclerosis and any history of tick bites

POSTERIOR UVEITISo Defined as inflammation that is limited to the

posterior segment of the eyeo Ii is associated with the highest risk of severe

vision losso There are many systemic causes for posterior

uveitis Ocular toxoplasmosis is the most common cause

of posterior uveitis and accounts for 90%

o Noninfectious causes may include immunologic or allergic origins, unknown causes and masquerade conditions (including neoplasm)

o Ocular diseases associated with posterior uveitis include; Sarcoidosis Toxoplasmosis Eales’ disease Frosted branch angitis Acute retinal necrosis Retinal arteritis and aneurysms Birdshot choroiditis Pars planitis

o Ancillary testing are useful for diagnosis Fluorescein angiography Optical coherence tomography B-scan ultrasonography Visual field testing

LABORATORY TESTINGo Indications for laboratory testing

Bilateral uveitis Affects an atypical age group Recurrent, recalcitrant or hyperacute uveitis Patients with uveitis that worsens with tapering Uveitis that is causing decreased visual acuity Immunocompromised patients

o Minimal laboratory testing should include; Complete blood cell count Urinalysis (psoriatic arthritis, proteins) Lyme titers HLA-B27 (ankylosing spondylitis) Antinuclear antibody (ANA) test (juvenile idiopathic

arthritis) Angiotensin converting enzyme (ACE) test (sarcoidosis) Veneral disease research laboratory (VDRL) test

(syphilis) Fluorescent treponemal antibody absorption (FTA-ABS)

test (syphilis)o Chest X-ray should also be performed when testing

for TB and sarcoidosis

LAB TESTS WHEN YOU SUSPECT SYSTEMIC DISEASE

Condition Clinical features Tests indicated

Ankylosing spondylitis Young male, low back pain, chest pain

HLA-B27, Sacroiliac X ray

Reiter’s syndrome Young male, arthritis, urethritis, conjunctivitis

HLA-B27, ESR, CRP

Juvenile idiopathic arthritis

Slight male predilection, sacrolitis, common

ANA, RF, knee radiograph

Inflammatory bowel disease

Ulcerative colitis, diarrhea, abdominal cramps

HLA-B27, GI referral for endoscopy

sarcoidosis African Americans, females, posterior segment inflammation ie vasculitis, vitris

ACE, chest X-ray or CT scan

Tuberculosis Prolonged cough, fever, chills, night sweats, weight loss

PPD, chest X-ray

Cont….Condition Clinical features Tests indicated

Syphilis History of sexual contact with infected person, rash, fever, malaise, headache, joint pain

FTA-ABS, VDRL, RPR

Toxoplasmosis Immunocompromised status, exposure to cats, hx of eating raw meat, punched-out retinal lesions

Toxoplasma IgG or IgM for acute acquired cases

Birdshot retinochoroidopathy

Diffuse atrophic choroidal granulomata, optic atrophy, maculopathy

HLA-A29

Lyme disease Recent tick bite Lyme Western BlotWegener’s granulomatosis

Sinus, pulmonary, kidney disease, scleritis

ANCA, sinus films, chest X-ray, serum creatinine

CURRENT TREATMENTS FOR UVEITIS

o The goal of uveitis treatment and management is to alleviate the patient’s symptoms and control inflammation

o Prior to initiating treatment, you must rule out any infectious condition

o Topical steroids are the mainstay of treatment for the majority of uveitis, but steroids injections and oral steroids are often needed in cases of intermediate and posterior conditions

o Steroids should always be used aggressively to treat and suppress the inflammatory response, with initial dose ranging from q1h to q.i.d.

o Using steroids aggressively In order to be effective, steroids should be pulse-

dosed frequently upon initial presentation, with a gradual taper over several weeks depending on the response to treatment

Steroids should not be tapered until there is a two-grade improvement in clinical signs (eg 4+ cells to 2+ cells), and should not be stopped until there is a complete resolution of all cells, flare and macular edema

o Compliance with these drops is crucial for the resolution of uveitis, so emphasize its importance to the patients

o Steroid treatment should be continued even after the resolution of all cell and ocular inflammation Patients should a tapering regimen after resolution

to decrease the risk of any rebound effect

o Pred Forte (prednisolone acetate 1%) has been the gold standard in the uveitis treatment and continues to be a very effective treatment today

o Whenever you prescribe steroids, always monitor for increased IOP and cataract formation

o Side effects of topical steroids Increased IOP Cataract formation Delayed wound healing or epithelialization Reactivate latent herpes simplex infections Potentiate bacterial, fungal or acanthamoebal

infections

o When considering IOP lowering agents, use caution with prostaglandin analogues because they may exacerbate the inflammatory response

TREATMENT CONSIDERATIONSo If you have a patient with diagnosed systemic

disease, chronic uveitis is often well controlled with immunomodulatory or antimetabolite systemic therapy Stay in contact with a rheumatologist

o Pain and photophobia are common symptoms in uveitis that can be treated effectively with cycloplegics Cycloplegics improve comfort by;

Immobilizing the inflamed iris and ciliary body Stabilizing the blood aqueous barrier to prevent the

leakage of proteins Breaking synechiae formation

The most popular cycloplegics used are homatropine 5% b.i.d., scopolamine 0.25% tds, atropine 1%

o Additional treatments for uveitis include; Sunglasses Topical or oral NSAIDs (for analgesia) Immunosuppressants Periocular steroid injections Intravitreal steroid injections Long and short-acting intravitreal steroid implants Intravitreal VEGF inhibitor injections Specific surgical procedures

REFERENCE Whitley W, Sheppard J (2011) The Basics of

Uveitis. Review of Optometry. Available from http://www.reviewofoptometry.com/continuing_education/tabviewtest/lessonid/107773/