三軍總醫院 蔡明霖醫師 M.D. Ph.D.

Uveitis and Sclera

Anatomy of eyeball

Uvea: vascular layer of the eye(Ocular branch of Ophthalmologic a.)iris, ciliary body, choroid. uvea

sclera

Eyeball:outer coat (cornea, sclera), middle vascular layer (uveal tract) inner sensory layer ( retina)

Origin of uveal vessel

4

3

5

2

Ocular branch 1. Central retinal artery 2. Anterior ciliary artery 3. long posterior ciliary artery 4. short posterior ciliary artery 5. Muscle Br

Internal carotid a.=>Ophthalmologic a.=>Ocular branch

Iris

anterior part of uveal tract

Iris 以 collarette 為界 ; 分成pupilary and ciliary 兩部份

Function of iris

• pupil open • Iris dilator muscle • cervical sympathetic trunk

• pupil close• Iris sphincter muscle • short ciliary nerve (brainstem: E-W Nu )

散瞳劑

副交感神經阻斷劑 :Atropine(1%) :2 weeks 。Scopolamine:1-3 days

Homatropine:1-3 days cyclopentolate(0.5%):24 hours

tropicamide (0.5%): 6 hours 。

Ciliary body

Function: aqueous productionaccommodation

middle part of uvea

Histology

Stroma : ciliary muscle (accommodation ) circular muscle=>near ( lens thickening) radial muscle=>far (lens thinning)

Epithelium:

pigmented epithelium

non-pigmented epithelium

(aqueous formation)

Accommodation

near lens thickening parasympathetic fiber ciliary circular M. contraction zonular relax

Far lens thinning sympathetic fiber ciliary radial M. contraction zonular contraction

睫狀肌鬆弛劑

•副交感神經阻斷劑 :Atropine(1%) :2 weeks 。Scopolamine:1-3 daysHomatropine:1-3 days cyclopentolate(0.5%):24 hourstropicamide (0.5%):6 hours 。

Choroidal function

• Retina : blood supply

(Inner 1/3 retina vessel; outer 2/3 choroid)

• light-absorbing layer

Uvea and scleral disease

• Uveitis

• Uveal tumor

• Scleral diseased

I Disease of Uvea Tract

• Uvea inflammation:• Incidence 1/1000 case • Etiology: infection, neoplasm, immunology, unknown

•anterior uveitis 75%; post uveitis 25%•Classification: location, duration, inflammation

Uveitis: Classification

• Location: iritis or anterior uveitis, cyclitis or intermediate uveitis choroiditis or posterior uveitis.• Duration: acute-within 3 months chronic- exceed 3 months• Inflammation type : non-granulomatous : granulomatous (nodule>1mm) (Koppe`s nodule papillary margin Busacca`s nodule: iris surface)

hypopyron

synethiae

KP

Uveitis: anterior segment sign

Flares,cellsKeratic precepitation

HypopyonSynechiae

hypopyron

synethiae

Uveitis: posterior segment sign

Intermediate uveitis: snowballs, string of pearls)

Retina: Retinal vasculitis

Choroid: Choroiditis, granuloma

snowballs vasculitis

Choroiditisgranuloma

Synptom/Sign of uveitis Sign/Symptom Description Pathogenic Mechanisms

Flare Milkiness of aqueous humor Protein is transudate from uveal vessels

Cells Inflammatory and pigmented cells in AC White blood cells released from uveal vessels

Fibrin (cyclytic membrane)

Coagulation of exudates in AC (only seen in severe cases)

Extreme inflammation with accumulation of fibrin 

Iris nodules: Koeppe and Busacca

Fluffy white nodular precipitates on inner surface of pupillary margin (Koeppe) or on surface of iris (Busacca) (seen in some systemic based diseases)

Inflammatory cellular infiltration into iris stroma

Keratic precipitates (KP's)

Deposits of inflammatory cells on endothelium. inferiorly; fine white (non-granulomatous) to giant waxy mutton fat (granulomatous); may be pigmented

Inflammatory cells from iris and uveal vessels which stick to corneal endothelium

Hypopyon Purulent exudate in lower AC (seen in severe cases)

Purulent Exudation from inflamed uveal vessels

Grading Cells and Flare

Grade Aqueous Cells Grade Flare

0 None 0Optically Empty Compared Bilaterally

12-5 Cells Seen in 45 Seconds or One Minute

1Faint: Haze or Not Equal Bilaterally

25-10 Cell Seen at Once

2Moderate: But Iris Detail Still Clear

3Cells Scattered Through Out Beam 20 or More

3Marked: Iris Details Becoming Hazy

4Dense Cells in Beam, More Than You Can Count

4Dense Haze: With Obvious Fibrin Collecting on Iris

Synptom/Sign of uveitis

IOP variation Low IOP is characteristic; glaucoma may develop as complication

Low IOP from decreased aqueous production; high IOP is seen if TM becomes clogged with inflammatory debris

Synechiae Adhesions of the iris to the lens in the pupillary zone (posterior synechiae) or of iris to angle structures (peripheral anterior synechiae) -- these develop during acute phase and persist indefinitely if not broken

heavy exudation of protein (posterior); shallowing of AC from pupillary block, organization of exudates in angle, or from swelling of iris root (PAS)

Conjunctival and perilimbal injection

Pink to violet circumlimbal episcleral vessels (ciliary flush)

Inflammatory vasodilation of radial episcleral vessels

Cataract Opacification of crystalline lens From nutritional deprivation of lens fibers; or as a toxic response to inflammatory cell breakdown; or from topical or systemic steroid use

Small pupils Not always present; miosis relative to other pupil

Vasodilation of iris vessels; prostaglandin release

Diagnosis of uveitis

• Find curable uveitis: Trauma; Infection; Neoplasm• Find controllable disease Systemic associated ocular inflammation: rheumatoid arthritis; lupus Specific ocular inflammation

Diagnosis of uveitisFind curable uveitis

•Trauma : Hx•Infection: Bacteria (complete blood count; culture) Fungus (complete blood count; culture, culture) Parasite (complete blood count; culture, eosinophil) Virus: PCR; Serology: VDRL, HIV, Torch marker • Neoplasm: CBC, image study( PET)

Diagnosis of uveitisFind controllable disease

• Systemic associated ocular inflammation: ankylosing spondylitis( image study, HLA-B27) Rheumatoid arthritis ( image study; CRP) lupus( CBC; anti-ds DNA) sarcoidosis( CxR; biopsy) Behcet disease (oral ulcer)

• Specific ocular inflammation Vogt-Koyanagi-Harada's Disease Sympathetic ophthalmia

Uveitis treatment

Mandatory : 1. Treatment of underlying disease, if known ( traum

a, infection, neoplasm) 2. Cycloplegic agent 3. topical steroid Optional : 1. Periocular or systemic steroids: unresponsive to topical steroid 2. Immunosuppressors, anti-TNF therapy sight-threatening inflammation which has been unresponsive to steroids 3. control elevated intraocular pressure

Specific ocular uveitis• Anterior uveitis

– HLA-B27 associated uveitis(20-40%)– Sarcoidosis (15%) – Posner-Schlossman Syndrome (1-5%)

Posterior uveitisOcular toxoplasmosis(8-40%)Behcet disease (5%)Vogt-Koyanagi-Harada's Disease

Sympathetic ophthalmia

HLA-B27 associated uveitis

S/S: flares, cells, fibrin, seldom KPDx: 1. clinical picture 2. HLA-B27 positive. 3. associated systemic disease

Treatment: 1. Cycloplegic agent 2. Steroid3. NSAID4. anti-TNF therapy

HLA-B27 associated system disease

• Treatment: control uveitis, consult: CV, RIA , REH

• AS :systemic anti-inflammatory agent CV consult(heart block, aortic insufficiency) Reiter syndrome: systemic antibiotic Psoriasis: analgesics, immunosuppressive

AS(55-90%)

Psoriasis3-4%

Reiter syndrome

(8-21%)

sarcoisosis

• S/S Hilar enlaragement Granulomatous uveitis Mutton fat KP• Dx : biopsy, non-caseous granuloma

• Treatment Cycloplegic agent Steroid immunosuppressor

Posner –Schlossman syndromn (Glaucomatocyclitic crisis)

S/S: KP, IOP elevation Eti: prostaglandin induced trabeculitis Dx: clinical criteria 1. Fine KP 2. trabeculitis 3. IOP elevation

TX: 1. Steroid 2 atropine 3 control IOP 4 avoid miotic 5 avoid prostagradin

Ocular toxoplasmosis

S/S: central chorioretinal scar , vitritisEti: Toxoplasma gondii raw meat (cyst); contaminated vegetable (oocyst)Dx: serum anti-toxoplasma gondii antibody PCR ; biopsy - trophozoite, cystTx: 1. Sulfadiazine 2 clindamycin 3. Prednisolone 4. pyrimethamine (folic acid)

Toxoplasmosis

Behcet’s disease

S/S: systemic vasculitis, young male, HLA B51 Dx: clinical picture 1. Oral ulcer 2. Skin Lesions 3. Genital ulcer 4. Ocular inflammation

Eti: unknown. infection-induced autoimmune process to vessel endothelium is the most likely mechanism. TX: 1. Steroid 2 immunosuppressor

MAJOR CRITERIA MINOR CRITERIA

Recurrent Oral Aphthous Ulcers (pain) Arthritis (heat, effuse, limitation)

Skin Lesions:**Erythema nodosum-like lesions**Folliculitis

Epididymitis

Genital Ulcers( Gastrointestinal Involvement

Ocular Disease:**Iridocyclitis with hypopyon**Posterior Uveitis with retinal vasculitis

Vascular Involevement:**Thrombophlebitis

Neurologic Symptoms

Complete 　 Presence of all major criteria

Incomplete

3 major criteria2 major + 2 minor criteriaocular disease + 1 major criterionocular disease + 2 minor criteria

Suspect 2 major criteria

Possible 1 major criterion

Diagnosis

Vogt-Koyanagi-Harada's Disease (Uveomenigitic Syndrome)

• S/S: bilateral, painful visual loss associated with posterior or panuveitis. • pathogenesis: unknown. An autoimmune process to melanocyte is the most likely mechanism. • S/S :

Prodromal phasemeningeal phase, patients have headache, fever, and meningitis.

Uveitic phaseThe uveitic phase, which lasts for several weeks

Convalescent phaseThis phase is characterized by dermatologic changes

Chronic phaseThe chronic phase consists of smoldering panuveitis with acute episodes of anterior uveitis.

• Treatment: steroid or immunosuppressor for 6 months

Vogt-Koyanagi-Harada's DiseaseDiagnostic criteria ( American Uveitis Society, 1978)

1. No history of ocular trauma or surgery

2. At least 3 out of the following 4 criteria:

Bilateral chronic iridocyclitis Bilateral posterior uveitis

•Cutaneous findings: alopecia,

poliosis, or vitiligo (late)

•Neurological signs: tinnitus, neck stiffness, cranial nerve or central nervous system dysfunction, or cerebrospinal fluid pleocytosis

Sympathetic ophthalmia

• S/S: injury in one eye , granulomatous i

nflammation developed in following eye

• Pathogenesis: granulomatous inflammation to to melanocyte • Dx: Dallen-Fuch nodule•Treatment : repair would steroid or immunosuppressor for 6 months

Uveal melanoma• most common primary intraocular

malignancy• How to DD from benign tumor:

MSOFT

1. Ill-defined margin 2. symptoms (Rapid growth) 3. orange pigmentation 4. fluid 5.thinkness>2mm

II Uveal tumor

•Uveal melanoma 最常見的原發性眼內惡性腫瘤•眼內最常見的腫瘤為 metastatic uveal tumor•女性最常見的的轉移性腫瘤 ,來源為乳癌•男性最常見的的轉移性腫瘤 ,來源為肺癌

Uveal melanoma• Pathology:spindle cell A, spindle cell B, mixed type

• Treatment

Photocoagulation, brachytherapy, enucleation, cyberknife

III Sclera and scleral disease

Sclera histology : two layerEpisclera, Scleral stroma( 越後面越厚 )

•Sclera: white outer covering of the eye•Muscle insertion : danger site of eyeball rupture MR 5.5; IR 6.5; LR 7.0; SR 7.8mm

Episcleritis: episcleral tissue inflammation

S/S: red eye episcleral vessel engorgement(between the conjunctiva and the sclera)

Eti: allergy, unknown,…DD: epinephrine => bleach Tx: steroid

ScleritisScleritis: an inflammation of the sclera stromaS/S: red eye Eti: unknown, 50% associated with immune disease such as : rheumatoid arthritis, Crohn’s disease, Wegener’s granulomatosis, metabolic disorders, infections and chemical or physical injuries.DD: epinephrine => scleral vessel bleach do not bleach Tx: 1. Steroid 2 immunosuppressor 3 scleral graft

Video for uveitis Biopsy

THANKS

Find systemic disease

Diagnostic imaging • Chest x-ray (TB, sarcoidosis, histoplasmosis, tumor) • Sacroiliac films (HLA-B27, Reiter, ankylosing spondylitis) • Orbital image (tumor, foreign body, thyroid, scleritis) • Skull films (congenital toxoplasmosis) • Joint films (rheumatoid, HLA-B27, JRA, lupus, gonorrhea) • Gallium scan (sarcoidosis, infection, metastasis)

HLA B27

VKH

VKH

• minimum of 6 months, has been shown to improve the prognosis by reducing the length of disease, increasing the incidence of a convalescent phase, and decreasing the extraocular manifestations.

SO: 須找出傷口

Sarcoidosis

• The initial dose is 30 to 60 mg of prednisone daily for 8 to 12 weeks, followed by slow tapering over 6 or 12 weeks to establish the minimal effective dose.5,6 Pulsed intravenous methylprednisolone might be necessary in some cases. A maintenance dose of oral corticosteroid at 10 to 15 mg per day in alternate days should be given at least for 3 months.

HLA-B27 associated system disease

• Treatment: control uveitis, consult: CV, RIA , REH

• AS :systemic anti-inflammatory agent CV consult(heart block, aortic insufficiency) Reiter syndrome: systemic antibiotic Psoriasis: analgesics, immunosuppressive

AS(55-90%)

Psoriasis3-4%

Reiter syndrome

(8-21%)

Find systemic disease

Diagnostic imaging • Chest x-ray (TB, sarcoidosis, histoplasmosis, tumor) • Sacroiliac films (HLA-B27, Reiter, ankylosing spondylitis) • Orbital image (tumor, foreign body, thyroid, scleritis) • Skull films (congenital toxoplasmosis) • Joint films (rheumatoid, HLA-B27, JRA, lupus, gonorrhea) • Gallium scan (sarcoidosis, infection, metastasis)