• Anterior Uveitis
• Intermediate Uveitis
• Posterior Uveitis
• Panuveitis
• AIDS and the eye

• Common lab tests
• Behçet syndrome
• Fuchs heterochromic iridocyclitis
• Glaucomacyclitic crisis (Posner Schlossman)
• Herpetic iritis
• Idiopathic
• IOL- related iritis
• JRA-related iridocyclitis
• Kawasaki syndrome
• Lens related Uveitis
• Low-grade infectious endophthalmitis (P. acnes)
• Sarcoidosis
• Seronegative spondyloarthropathies
• Syphilis
• Traumatic iritis

• Common lab tests
• Intraocular lymphoma
• Lyme disease
• Multiple sclerosis
• Pars planitis
• Sarcoidosis

• Common lab tests
• Chororetinitis with vitritis
• Acute retinal necrosis (ARN) (HSV, VZV, CMV)
• Birdshot choroidopathy (vitiliginous chorioretinitis)
• Cysticercosis
• Infectious endophthalmitis
• Lymphoma
• Multifocal choroiditis with panuveitis
• Onchocerciasis
• Progressive outer retinal necrosis (PORN)
• Sarcoidosis
• Sympathetic ophthalmia
• Syphilis
• Toxocariasis
• Toxoplasmosis
• Tuberculosis
• Vogt-Koyanagi-Harada syndrome (VKH)
• Chorioretinitis without vitritis (usually)
• Neoplastic (metastasis)
• Ocular histoplasmosis
• Onchocerciasis
• Serpiginous choroidopathy
• White dot syndromes:
  • Acute multifocal placoid pigment epitheliopathy (AMPPE)
  • Acute retinal pigment epithelitis (ARPE)
  • Multiple evanescent white dot syndrome (MEWDS)
  • Punctate inner choroiditis PIC
• Vasculitis
• Beçhet syndrome
• Systemic lupus erythematosis
• Polyarteritis nodosa
• Wegener granulomatosis

• Cysticercosis
• Infectious Endophthalmitis (bacterial)
• Leptospirosis
• Lyme Disease
• Lymphoma
• Multifocal choroiditis and panuveitis
• Onchocerciasis
• Sarcoidosis
• Subretinal fibrosis and uveitis syndrome (SFU)
• Sympathetic Ophthalmia
• Syphilis
• Toxocariasis
• Toxoplasmosis
• Tuberculosis
• Vogt-Koyanagi-Harada (VKH) syndrome

Common Lab tests for Anteior Uveitis

• ACE level (sarcoidosis)
• ANA (JRA classification)
• CBC (leukemia)
• Chest X-ray (sarcoidosis, tuberculosis- may be supplanted by CT)
• ELISA, IFA for lyme dz
• FTA-ABS (syphilis)
• GI series or biopsy (ulcerative colitis or Crohn disease)
• HLA-B27 (ankylosing spondylitis & Reiter syndrome)
• TB skin test
• Serum lysozyme (sarcoidosis)

Common Lab tests for Intermediate Uveitis

• ACE level (sarcoidosis)
• Chest X-ray (sarcoidosis, tuberculosis- may be supplanted by CT)
• ELISA for toxocariasis
• FTA-ABS (syphilis)
• Serum lysozyme (sarcoidosis)
• Serum protein electrophoresis (sarcoidosis)
• TB skin test

Common Lab tests for Posterior Uveitis

• ACE level (sarcoidosis)
• Blood cultures, viral cultures, Antibody levels (CMV, HSV, Rubella)
• ELISA for Toxoplasmosis, Toxocara, Lyme dz
• FTA-ABS (syphilis)
• Serum electrophoresis (sarcoidosis)
• Serum lysozyme (sarcoidosis)

• Fulminant, necrotizing viral retinal infection
• Bilateral in 33% (BARN) fellow eye can follow up to 26 years later
• Most are not immunocompromized
• Etiologies: Varicella-zoster virus, herpes simplex virus type 2, cytomegalovirus
• Clinical appearance: AC inflammation (minor to severe), heavy vitritis, retinal arteriolitis, multifocal yellow-white peripheral retinitis- may coalesce to form confluent 360º "creamy" retinitis, posterior pole usually spared.
• Treatment:
• Acyclovir IV 1500 mg/m² per day in 3 divided doses over 10-14 days
• Gancyclovir (intravitreal) 200 microgram/0.1ml in the setting of HIV and poor systemic tolerance of gancyclovir
• Corticosteroids after 24-48 hours of acyclovir
• Aspirin or other anticolagulation agents if associated hypercoagulable state
• Multiple posterior retinal breaks often occur
  • Laser demarcation sometimes helpful
  • Scleral buckle, vitrectomy and silicone oil more successful than standard scleral buckle
• Prognosis: Poor visual prognosis
  • condition slowly resolves over 1-2 months
  • 65% have vision worse than 20/200

Behçet Syndrome

• Generalized occlusive vasculitis of unknown cause. Chonic and tends to recurr every 2-4 years.
• Classic triad: 1) Acute iritis with hypopion, 2) Aphthous oral ulcers, 3) Genital ulcers
• Epidemiology
• Characteristics
• Lab Tests
• Treatment

Infectious Endophthalmitis

Intraocular lens related Uveitis

• Uveitis most likely to occur with use of rigid closed loop anterior chamber lenses (no longer used in U.S.)
• silicone IOL's have been implicated in the past with poor data to support the accusations
• Polypropylene haptics have enhanced bacterial and leukocyte binding
• In the postoperative period, make sure to rule out infectious endophthalmitis
• The iris is chafed by the IOL loops causing irritation and inflammation
• Incidence with modern lenses is ~1% or less.
• Intermittant corneal touch may lead to endothelial damage, corneal decompensation and microcystic edema
• Cystoid macular edema also possible
• UGH syndrome: uvitis-glaucoma-hyphema syndrome
  • becoming less common
  • caused by irritation of the iris root by warped footplates or faulty rigid anterior chamber IOL's
  • Flexable IOL's are less traumatic
  • Perepherial and superior corneal edema
  • Chronic low grade iridocyclitis
  • perepherial anterior synechaie
  • intermittent microhyphemia
• Treatment: remove and exchange IOL, treat glaucoma, corticosteroids or macular edema and uveitis, penetrating keratoplasty often needed for corneal decompensation.

Lens Related Uveitis

• Phacoantigenic endophthalmitis (phacoanaphylaxis)
• Phacotoxic uveitis
• Phacolytic glaucoma
• The above conditions may show considerable overlap in their clinical presentation

Phacotoxic uveitis

• An inflammation of the anterior chamber following lens extraction, especially if there are retained nuclear fragments
• Mild to moderate inflammation, less than occurs with phacoanaphylaxis
• Better term might be phacoallergic uveitis since the lens proteins are causing an inflammatory response with out the epitheloid macrophage response
• Treatment: corticosteroids, might need to remove retained nuclear fragments if inflammation persists

Seronegative Spondyloarthropathies

• HLA-B27 genotype
• Ankylosing spondylitis
• Inflammatory bowel disease
• Reiter syndrome
• Psoriatic arthritis
• Postinfectious (reactive) arthritis

HLA-B27 genotype

• Short arm of Chromosome 6
• Present in 1.4%-8% of normal population
• 50-60% of patients with acute iritis are positive
• Testing should be preformed on those with recurrent anterior nongranulomatous uveitis
• If HLA-B27 is found in asymptomatic patient-risk of developing spondyloarthritis or eye disease is 1 in 4

Ankylosing Spondylitis

• Lower back pain and stiffness
• Acute nongranulomatous anterior uveitis
• X-ray evidence of sacroilitis (sacroiliac view not lumbosacral spine film) and vertebrae fusion
• HLA-B27 is found in 88%
• Pulmonary apical fibrosis can occur
• Aortitis in 5%, associated with aortic valve insufficency

Inflammatory Bowel Disease

• Ulcerative colitis
  • Acute anterior iritis in 5-12%
  • Occasionally the bowel disease follows the onset of iritis
  • 60% have HLA-B27
  • 20% have sacroilitis
  • If sclerouveitis present, the patient tends to be HLA-B27 negative and symptoms are more like rhematoid like without sacroilitis
• Crohn disease
  • Acute anterior iritis in 2.4%

Reiter Syndrome

• Classic triad: 1.) Urethritis 2.) Polyarthritis 3.) Conjunctivitis and Iritis
• HLA-B27 is present in 85-95%
• Young adult males most common, 10% female
• Can be triggered by episodes of diarrhea or dysentary
• Triggering infections: chlamydia, ureaplasma, shigella, salmonella, yersinia
• Clinical findings:
  • Arthritis of knees, ankles, feet and wrists, often asymmetric involvement
  • Sacroilitis in 70%
  • Major diagnostic critera: (American Rheumatologic Association)
    • Urethritis
    • Polyarthritis
    • Iritis/Conjunctivitis
    • Keratoderma blennorrhagicum- scaly, erythematous, rash of palms and soles, resembling a pustular psoriasis
    • Circinate` balantitis- persistant, scaly, erythematous, circumferential rash of the distal penis
  • Minor diagnostic criteria:
    • plantar fasciitis
    • Achilles tendinitis
    • sacroilitis
    • nail-bed pitting
    • palate ulcers
    • tongue ulcers
• Eye findings
  • Conjunctivitis- mucopurulent and papillary
  • Punctate and subepithelial keratitis
  • Acute nongranulomatous iritis frequent
  • Iritis can become bilateral and chronic

Psoriatic arthritis

• Anterior nongranulomatous uveitis can occur with psoriasis if arthritis is also present
• Iritis does not occur if arthritis is absent
• 20% develop sacroilitis
• Association with inflammatory bowel disease
• Typical findings: erythematous hyperkeratotic rash, distal interphlangeal joint inflammation, subungual hyperkeratosis, oncyolysis, nail bed pitting.

Toxoplasmosis

• Epidemiology
• Organism
• Clinical Manifestations
• Diagnosis
• Treatment

Toxoplasmosis- Epidemiology

• Estimated 500 million have antibodies worldwide
• 50% of adult population in US have had asymptomatic infection
• 60% of those over 80 years have been infected
• Only 10% under age 5 have had the infection
• And only 30% of the women of child bearing age have antibodies
• 28-55% of all cases of posterior uveitis
• Most cases are presumed reactivation of congenital infection
• 2 to 6/1000 women acquire infection while pregnant, 40% risk of transmission to fetus.
• Of infected infants: 70% chorioretinal scars, 5% will die or severe disability, 1-2% severe visual impairment
• Northern Brazil has high rate of acquired disease

• Toxoplasma gondii -obligate intracellular protozoan
• First isolated from the brain of a "gondii" (North African Rodent)
• Cat family is definitive host, can infect other mammals and birds
• Oocysts found in intestinal tracts of cats
• Cysts ingested (most likely) because of poor hygiene and injesting infected pork and chicken but probably not beef
• Can survive outside host for up to 1 year
• Two forms in humans: cysts or tachyzoites.
• Propensity for cardiac and skeletal muscle and neural tissue (brain & eye)

• Systemic: (10% of affected neonates, rare in adults)
  • 90% lympadenopathy
  • fever, malaise, vomiting, diarrhea, anemia, jaundice, hepatosplenomegaly, sore throat (adults)
  • CNS- abnomal CSF, convulsions, intracranial calcifications, hydrocephalus, microcephalus, mental retardation
  • immunocompromised- more likely to have fulminant CNS disease
• Ocular
  • Keratic Precipitates, anterior chamber cell and flare, posterior synechia, cataract
  • Retinochoroiditis- active or inactive
    • Active: white elevated retinal lesion with cells and protein exuding into vitreous
    • Inactive: pigmented flat scar
  • Vitritis- concentrated over lesion, scaffolding of vitreous strands
  • Macular edema
  • Retinal vasculitis
  • Visual field defect in area of scar
  • Flourscein angiography of active lesion shows early blockage and subsequent leakage
• Atypical presentations
  • In early infection: gray-white fine punctate lesions in deep retina and RPE, progress to more classic lesions
  • Papillitis, vitreal inflammation, nerve fiber bundle defects
  • Bullous like inflammatory lesions in mid-periphery
  • Wide ring-like lesion near extreme periphery resembling pars planitis
  • Scleritis
  • Microphthalmos
  • Cataract
• Reasons for vision loss
  • Vitreal inflammation causing clouding
  • Lesion in posterior pole with edema affecting fovea
  • Lesion in fovea
  • Subsequent choroidal neovascularization

• Typical lesions are supportive of diagnosis
• Toxoplasmosis titers are supportive
  • IgM titers- can be missed  (mothers IgM do not cross placenta)
  • IgG titers- high rate of false positives (mother's IgG are gone by 4-6 months)
  • Immunoflourescence, ELISA
  • Sabin-Feldman dye test- older test to detect toxo specific IgG
• Western blot for Toxo antigens
• PCR and Southern Blot for Toxo DNA
• CT of the brain if congenital toxoplasmosis suspected
• In all rule out: Tuberculosis and Syphilis
• In newborn rule out: CMV, HSV, retinoblastoma, Coats disease, candidiasis, AIDS, Aicardi syndrome
• Conditions resembling ocular toxoplasmosis: nocardiosis, sporotrichosis, cryptococcosis, choroidal dystrophies, histoplasmosis, CHRPE, macular colobomas, traumatic scars, Best Disease, toxocariasis

• Should you treat it at all? The following are potentially reasons to treat:
  • Lesion within temporal arcade
  • Lesion next to optic nerve or large vessel
  • Lesion has induced large degree of hemorrhage
  • Vision drop of > two lines
  • Multiple recurrences with vitreal contraction
• No truly randomized, controlled clinical trials to compare efficacy of various treatments
• Generally 4-6 weeks, multi-drug regimens
• Medications:
  • Sulfadiazine 1g PO QID
  • Pyrimethamine 75-100mg load and 25-50mg PO BID (bone marrow suppression, nausea)
    • Use concurrently with : Folinic Acid 3-5mg PO 3 times/week (Baseline CBC, follow q week)
  • Clindamycin 150-300mg PO TID-QID (reduces recurrence?, risk of pseudomembranous colitis)
  • Trimethoprim-sulfamethoxazole (DS) 1 PO BID
  • Atovaquone (Mepron) 750mg PO BID (kills cysts in vitro)
  • Tetracycline 2g load and 250mg PO QID (to replace clindamycin)
  • Prednisone 20-60 mg/day not used alone.

Toxocariasis

• Epidemiology
• Clinical Presentation
• Diagnosis
• Treatment

Toxocariasis- Epidemiology

• Caused by intestinal parasite of dogs or cats: Toxocara canis or Toxocaris cati (only dog organisms have been isolated from human eye)
• Children injest ova from dirt or other objects contaminated by dog or cat feces including improperly cleaned foods
• Ova produce larvae that invade intestine then blood and lymphatic vessels on course to liver, lung and eyes
• As organisms move through the retina they leave hemorrhage, infammation and necrosis- eosinophilic granuloma
• Incidence unknown
• Average age of infecton is 7-8 years with range from 2-9 years.

Toxocariasis- Clinical Presentation

• Chronic unilateral uveitis
• Granuloma: white, dome-like retinal lesion in the macula or periphery
• Vitreous opacification overlying an eosinophilic granuloma
• Exudative retinal detachment
• Posterior synechaie
• Cyclitic membrane

Toxocariasis- Diagnosis

• Typical lesion seen
• ELISA specific for Toxocara available
• Elevated eosinophiles in perepherial blood
• Eosinophiles in aqueous
• Granuloma usually does not calcify (contrast to retinoblastoma)

Toxocariasis- Treatment

• Active inflammation may respond to topical, periocular or systemic corticosteroids
• Intraocular steroid has also been used recently
• Inflammation begins after larvae die
• Thiabendazole is effective against living toxocara (if seen moving in the retina)
• Pars plana vitrecomy and lensectomy may be necessary if a cataract or cyclitic membrane forms or significant vitreous opacification occurs
• Prognosis is worse for eyes with chronic inflammation, perepherial granulomas may distort the macula and affect central vision

• Epidemiology
• Systemic signs/symptoms
• Ocular signs/symptoms
• Diagnosis
• Treatment

• Rare cause of posterior or panuveitis.
• Chronic, diffuse, granulomatous uveitis.
• No history of ocular injury.
• Most commonly Asian or American Indian, 30-50 y/o.
• Mechanism possibly immune reaction to melanin-associated protein, melanocytes or RPE.

VKH- Systemic Signs & Symptoms

• headache
• hearing loss, tinnitis, dysacusis
• stiff neck, loss of consciousness, paralysis, seizures, fever, coma,
• hemiparesis, focal neurologic deficits,
• transient lymphocytosis in CSF,
• alopecia, vitiligo, poliosis, (skin and hair signs in 30% and occur several weeks to months after onset of ocular inflammation)

VKH- Ocular Signs & Symptoms

• Bilateral vision loss, severe pain, redness, photophobia,
• AC cell moderate to severe with seclusion of pupil, keratic precipitates, synechiae, perilimbal vitiligo,
• hypotony, exudative choroidals,
• optic neuropathy, with swollen disc,
• vitreous opacities, CME, exudatitive retinal detachment and often spontaneous reattachment.
• Focal areas of RPE atrophy and hyperpigmentation.
• "Sunset glow fundus"- depigmentation of the choroid with orange-red discoloration with healing.

VKH- Diagnosis

• Rule out sympathetic ophthalmia.
• FFA- mutiple areas of subretinal leakage early.
• U/S shows diffuse retinal thickening.
• LP showing lymphocytosis .
• HLA-DR4 strongly associated.

VKH- Treatment

• Systemic, local and periocular steroids
• cycloplegic/mydriatics
• Occasionally cyclosporine or another immunosuppressive.
• Watch for PAS and subsequent glaucoma, subretinal neovascularization, cataract and phthisis bulbi.