Uveitis

8 Uveitis



PATHOPHYSIOLOGY

CLASSIFICATION

ANTERIOR UVEITIS

INTERMEDIATE UVEITIS

POSTERIOR UVEITIS

ENDOPHTHALMITIS

PANUVEITIS

MASQUERADE SYNDROMES

DIFFERENTIAL DIAGNOSIS OF UVEITIS WITH ASSOCIATED SIGNS

SURGERY AND UVEITIS


Pathophysiology





Inflammatory reaction



Acute: chemical mediators (histamine, serotonin, kinins, plasmin, complement, leukotrienes, prostaglandins)

Chronic: cellular infiltrates
NONGRANULOMATOUS: lymphocytes, plasma cells

GRANULOMATOUS: epithelioid and giant cells (Langhans’, foreign body, Touton)
3 PATTERNS: diffuse (e.g. VKH syndrome), discrete (e.g. sarcoidosis), zonal (e.g. lens-induced)


Retinal S-antigen



Protein found in human retinal photoreceptors and pineal gland

Most potent uveitic antigen; thought to be an enzyme located in rod outer segments

In animal model: produces uveitis when injected into nonocular sites (experimental autoimmune uveitis [EAU]; type 4 hypersensitivity); removal of thymus prevents EAU (supports T cell-mediated basis of inflammatory response)

Human diseases that resemble EAU: VKH, sympathetic ophthalmia, birdshot retinochoroidopathy; lymphocytes from these patients develop an in vitro proliferative response to retinal S-antigen, suggesting an autoimmune basis for these diseases


Classification





Pathology


nongranulomatous, granulomatous



Etiology


infection, immune response, malignancy, trauma, chemical, idiopathic



Location


sclerouveitis, keratouveitis, anterior uveitis (iritis), iridocyclitis, lens-induced uveitis, intermediate uveitis, endophthalmitis (infection or inflammation of the vitreous, anterior chamber, ciliary body, and choroid), posterior uveitis (retinitis, choroiditis, vasculitis), panuveitis (endophthalmitis and involvement of the sclera)



Anterior uveitis


Inflammation of iris (iritis) and ciliary body (cyclitis)


Most common cause of anterior uveitis in adults is idiopathic (followed by HLA-B27 associated)


Most common cause of acute, noninfectious, hypopyon iritis is HLA-B27-associated iritis





Etiology



Children: JRA, ankylosing spondylitis, psoriatic arthritis, acute interstitial nephritis, Fuchs’ heterochromic iridocyclitis, sarcoidosis, postviral, HSV, Lyme disease, trauma, Kawasaki’s disease

50% have posterior component (toxoplasmosis in 50% with posterior component)

Young adults: HLA-B27 associated, sarcoidosis, syphilis, Fuchs’, Behçet’s disease, spillover from intermediate or posterior uveitis

Older adults: idiopathic, sarcoidosis, HZO, masquerade syndromes (peripheral RD, intraocular foreign body, JXG, multiple sclerosis, malignancies [retinoblastoma, leukemia, large cell lymphoma, malignant melanoma])


Classification



Nongranulomatous:
ACUTE: idiopathic, HLA-B27 associated (5% of general population; associated with acute, recurrent uveitis; usually starts unilaterally; associated with the following 4 disorders: ankylosing spondylitis, Reiter’s syndrome, psoriatic arthritis, inflammatory bowel disease), Behçet’s disease, glaucomatocyclitic crisis (Posner-Schlossman syndrome), HSV, Kawasaki’s disease, Lyme disease, traumatic, postoperative, other autoimmune diseases (lupus, relapsing polychondritis, Wegener’s granulomatosis, interstitial nephritis)

CHRONIC (duration >6 weeks): JRA, Fuchs’ heterochromic iridocyclitis

Granulomatous:
INFECTIOUS: syphilis, TB, leprosy, brucellosis, toxoplasmosis, P. acnes, fungal (Cryptococcus, Aspergillus), HIV

IMMUNE-MEDIATED: sarcoidosis, VKH syndrome, sympathetic ophthalmia, phacoanaphylactic


Symptoms


pain, photophobia, decreased vision, redness



Findings


conjunctival and episcleral injection, ciliary injection (circumcorneal flush from branches of anterior ciliary arteries), miosis (iris sphincter spasm), AC reaction; may have hypopyon, keratic precipitates, iris nodules, dilated iris vessels (occasionally, rubeosis), synechiae (posterior [iris adhesions to lens; seclusio pupillae is a complete adhesion that can result in iris bombe] or anterior [iris adhesions to cornea and angle]) (Figure 8-1)


Keratitic precipitates (KP): aggregates of white blood cells on corneal endothelium; typically located inferiorly and centrally (Figure 8-2)

May occur with any intraocular inflammation, most commonly with uveitis

May be white or pigmented, small or large, nongranulomatous (fine) or granulomatous (mutton fat), diffuse or focal
NONGRANULOMATOUS: composed of lymphocytes and PMNs

GRANULOMATOUS: composed of macrophages, lymphocytes, epithelioid cells, and multinucleated giant cells

DDX OF DIFFUSE KP: Fuchs’ heterochromic iridocyclitis, sarcoidosis, syphilis, keratouveitis, toxoplasmosis (rarely)

Iris nodules:
KOEPPE: located at pupil margin; occur in granulomatous and nongranulomatous uveitis

BUSACCA: located on anterior iris surface; occur only in granulomatous uveitis (Figure 8-3)

BERLIN: located in anterior chamber angle; occur in granulomatous uveitis

image

Figure 8-1 Severe idiopathic anterior uveitis with fibrinoid reaction.


(From Hooper PL: Idiopathic and other anterior uveitis. In Yanoff M, Duker JS [eds]: Ophthalmology, London, Mosby, 1999.)


image

Figure 8-2 Keratic precipitates in anterior uveitis.


(From Forster DJ: General approach to the uveitis patient and treatment strategies. In Yanoff M, Duker JS [eds]: Ophthalmology, London, Mosby, 1999.)


image

Figure 8-3 Chronic granulomatous uveitis demonstrating Busacca nodules.


(From Forster DJ: General approach to the uveitis patient and treatment strategies. In Yanoff M, Duker JS [eds]: Ophthalmology, London, Mosby, 1999.)



DDx of hypopyon


HLA-B27 associated, infection (keratitis, endophthalmitis), foreign body, Behçet’s disease, VKH syndrome, malignancy (leukemia, retinoblastoma), toxic (rifabutin)



DDx of uveitic glaucoma


HSV, HZV, Posner-Schlossman syndrome, Fuchs’ heterochromic iridocyclitis, sarcoidosis; rarely toxoplasmosis, syphilis, sympathetic ophthalmia



Diagnosis



Minimum: CBC with differential, urinalysis, VDRL and FTA-ABS

Expanded (for recurrent anterior [3 or more attacks], granulomatous, positive review of systems, or posterior involvement): ESR, ACE, ANA, ANCA, IL-10, PPD plus anergy panel, CXR or chest CT; consider Lyme test in endemic areas, HLA typing (25% with HLA-B27 develop sacroiliac disease, so obtain sacroiliac X-ray), HIV Ab test

Targeted approach:
RECURRENT UVEITIS, WITH BACK STIFFNESS UPON AWAKENING: rule out ankylosing spondylitis
HLA-B27

Lumbosacral spine imaging (CT)

GRANULOMATOUS UVEITIS: rule out TB and sarcoidosis
CXR

Upper body gallium scan

Angiotensin-converting enzyme ([ACE]; elevated in 60% with sarcoidosis; also in Gaucher’s disease, miliary tuberculosis, silicosis)

Lysozyme

Serum calcium

Liver function tests and bilirubin

PPD

CHILD WITH RECURRENT OR CHRONIC IRIDOCYCLITIS: rule out JRA (usually ANA-positive, RF-negative)
ANA

RF

HLA-B8

RETINAL VASCULITIS, RECURRENT APHTHOUS ULCERS, PRETIBIAL SKIN LESIONS: rule out Behçet’s disease
Skin lesion biopsy

HLA-B51 and -B27

PARS PLANITIS AND EPISODIC PARESTHESIAS: rule out multiple sclerosis (MS)
Brain MRI

Lumbar puncture

RETINOCHOROIDITIS ADJACENT TO PIGMENTED CR SCAR: rule out toxoplasmosis
Toxoplasma IgM and IgG titers

RETINAL VASCULITIS AND SINUSITIS: rule out Wegener’s granulomatosis
ANCA

CXR

Sinus films

Urinalysis

RECURRENT UVEITIS AND DIARRHEA: rule out inflammatory bowel disease (IBD)
GI consult

Endoscopy with biopsy

CHOROIDITIS, EXUDATIVE RD, EPISODIC TINNITUS: rule out Harada’s disease/VKH syndrome
FA

Lumbar puncture

Brain MRI

Audiometry

ELDERLY FEMALE WITH VITRITIS: rule out intraocular lymphoma or infection
Vitreal biopsy for culture or cytology

UNILATERAL IRIDOCYCLITIS, FINE WHITE KP, LIGHTER IRIS IN AFFECTED EYE: rule out Fuchs’ heterochromic iridocyclitis
IOP

Gonioscopy (fine-angle vessels)


Treatment


topical steroids, cycloplegic; may require systemic steroids, immunosuppressive agents, antibiotics


Poor response to steroids: Fuchs’, syphilis, toxoplasmosis, keratouveitis, Lyme disease, chronic postoperative endophthalmitis, ARN, CMV


Complications


iris atrophy, band keratopathy, cataract, glaucoma, cystoid macular edema



Ankylosing Spondylitis


90% HLA-B27-positive; typically young men



Symptoms


lower back pain and stiffness with inactivity (upon awakening in morning)



Findings


anterior uveitis (30%; recurrent in 40%), episcleritis, scleritis



Other findings


arthritis (sacroiliac and peripheral joints), heart (aortic insufficiency, heart block), colitis (10%), lungs (restricted chest expansion, apical fibrosis)



Sacroiliac X-ray


sclerosis and narrowing of joint space; ligamentous ossification can occur



Reiter’s Syndrome


Triad of conjunctivitis, urethritis, and arthritis


75% HLA-B27; males > females


Associated with infections: Chlamydia, Ureaplasma urealyticum, Yersinia, Shigella, Salmonella



Findings


mucopurulent conjunctivitis, keratitis, acute anterior uveitis



Diagnosis


3 major criteria, or 2 major and 2 minor criteria


Major:
Urethritis

Polyarthritis (knees, sacroiliac joints)

Conjunctivitis

Keratoderma blenorrhagicum (scaling skin lesion, often on feet and hands [20%]; similar to pustular psoriasis)

Minor:
Plantar fasciitis and Achilles tendinitis

Circinate balanitis

Painless mouth ulcers

Prostatitis

Cystitis

Spondylitis/sacroiliitis

Tendinitis

Recent history of diarrhea

Iritis/keratitis


Psoriatic Arthritis


Associated with HLA-B17 and HLA-B27


Uveitis does not occur in psoriasis without arthritis



Findings


conjunctivitis, dry eyes, anterior uveitis



Other findings


arthritis (hands, feet, sacroiliac joints), psoriatic skin and nail changes



Inflammatory Bowel Disease (IBD)


Uveitis occurs in ulcerative colitis (10%) and Crohn’s disease (3%)



Findings


conjunctivitis, keratoconjunctivitis sicca, episcleritis, scleritis, anterior uveitis, orbital cellulitis, optic neuritis



Other findings


arthritis, erythema nodosum, pyoderma gangrenosum, hepatitis, sclerosing cholangitis



Fuchs’ Heterochromic Iridocyclitis


Occurs in young adults; unilateral


Associated with chorioretinal scars (toxo)



Symptoms


blurred vision



Findings


diffuse small white stellate KP, minimal AC reaction, no posterior synechiae, iris heterochromia (diffuse atrophy of stroma, loss of iris crypts; involved iris is paler; 15% bilateral), fine-angle vessels (may bleed during gonioscopy, cataract surgery, or paracentesis) (Figure 8-4)


image

Figure 8-4 Fuchs’ uveitis


(From Hooper PL: Idiopathic and other anterior uveitis. In Yanoff M, Duker JS [eds]: Ophthalmology, London, Mosby, 1999.)



DDx of iris heterochromia


trauma (intraocular metallic foreign body), inflammation, congenital Horner’s syndrome, iris melanoma, Waardenburg’s syndrome (iris heterochromia, telecanthus, white forelock, congenital deafness), Parry-Romberg syndrome (iris heterochromia, Horner’s syndrome, ocular motor palsies, nystagmus, facial hemiatrophy), glaucomatocyclitic crisis, medication (topical prostaglandin analogues [Xalatan, Lumigan, Travatan]), nevus of Ota



Pathology


plasma cells in ciliary body



Treatment


poor response to steroids



Complications


glaucoma (60%), cataract (PSC; 50%)



Juvenile Rheumatoid Arthritis (JRA)


(See Ch. 5, Pediatrics/Strabismus)



Kawasaki’s Disease


(See Ch. 5, Pediatrics/Strabismus)



Lyme Disease


Due to Borrelia burgdorferi (spirochete)


Ocular involvement is usually bilateral


Affected organ systems: skin, CNS, cardiovascular, musculoskeletal



Findings (in stage 2 and 3 disease)


cranial nerve palsies (CN 7 most common), orbital myositis, follicular conjunctivitis, symblepharon, episcleritis, keratitis (multiple nummular stromal infiltrates), chronic granulomatous iridocyclitis with posterior synechiae and vitreous cells, intermediate or posterior uveitis, pars planitis, chorioretinitis, exudative RD, CME, BRAO, retinal vasculitis, papilledema, pseudotumor cerebri, optic neuritis, optic atrophy



Posner-Schlossman Syndrome (Glaucomatocyclitic Crisis)


Recurrent anterior uveitis and increased IOP; episodes are typically self-limited



Symptoms


unilateral pain



Findings


mild AC reaction, few or no KP, elevated IOP



Treatment


may require topical glaucoma medications to control IOP, steroids to control inflammation



Phacoanaphylactic Endophthalmitis


Immune complex disease (type 3 hypersensitivity reaction) when normal tolerance to lens protein is lost


Previous rupture of lens capsule in same or fellow eye, followed by latent period; with re-exposure to lens protein during surgery, zonal granulomatous uveitis occurs


Associated with trauma (80%)


May develop severe uveitis with hypotony, secondary open-angle glaucoma



Pathology


zonal pattern (PMNs infiltrate central lens material; epithelioid histiocytes and mononuclear cells around nidus)



Treatment


remove lens



Interstitial Nephritis


Rare; can be idiopathic or triggered by allergic reaction to medicines (antibiotics, NSAIDs)


Associated with acute anterior uveitis



Pathology


interstitial edema with mononuclear inflammatory cells; eosinophils can be present



Intermediate uveitis





Etiology


pars planitis, multiple sclerosis (5–25% have periphlebitis and intermediate uveitis), Lyme disease, sarcoidosis, Fuchs’ heterochromic iridocyclitis



Pars Planitis


Most common cause of intermediate uveitis (85–90%)


Usually young adults; females > males; 75% bilateral


Accounts for 25% of uveitis in children


Associated with HLA-DR15 and MS



Etiology


unknown; diagnosis of exclusion



Symptoms


floaters, decreased vision



Findings


light flare with a few KP, anterior vitritis, snowballs (white vitreous cellular aggregates near ora serrata; may coalesce to form peripheral fibrovascular accumulation [snowbank] over inferior pars plana and vitreous base), peripheral retinal periphlebitis, hyperemic disc, no chorioretinitis, no synechiae (Figure 8-5)


image

Figure 8-5 Inferior pars plana snowbank with attached snowballs.


(From Zimmerman PL: Pars planitis and other intermediate uveitis. In Yanoff M, Duker JS [eds]: Ophthalmology, London, Mosby, 1999.)



Pathology



Snowballs: epithelioid cells and multinucleated giant cells

Snowbank: preretinal membrane of fibroglial and vascular elements

Peripheral retinal veins: often have perivascular cuff of lymphocytes


DDx


sarcoidosis, toxoplasmosis, toxocariasis, syphilis, Lyme disease, MS


Multiple sclerosis: bilateral pars planitis can occur (80% bilateral, 20% unilateral); may present with band keratopathy, mild AC reaction, vitreous cells in a young patient; can also have cataract (PSC), epiretinal membrane, CME, retinal phlebitis


Treatment


(main indication is CME with reduced vision): periocular and oral steroids; consider immunosuppressive agents, vitrectomy, cryotherapy to areas of peripheral NV (controversial; can decrease leakage and macular edema, but can lead to retinal tears)



Prognosis


10% self-limited, 90% chronic (image with exacerbations)



Complications


cataract, retrolenticular cyclitic membrane, VH (from peripheral retinal neovascularization), tractional RD, CME (primary cause of vision loss, followed by cataract), band keratopathy



Posterior uveitis


Most common cause of posterior uveitis in adults is toxoplasmosis (followed by retinal vasculitis)





Signs


vitreous cells, membranes, opacities, inflammatory exudates (’snowballs’), vasculitis (opacification around vessels [sheathing {whole vessel}, cuffing {segment of vessel}]), exudates (candlewax drippings), retinitis, pigmentary changes (due to RPE inflammation), choroiditis (focal, multifocal, or diffuse), choroidal detachment



DDx of vitritis



Panuveitis: sarcoidosis, TB, syphilis, VKH, sympathetic ophthalmia, Behçet’s disease

Postsurgical/trauma: Irvine-Gass syndrome

Endophthalmitis

Choroiditis: acute posterior multifocal placoid pigment epitheliopathy (APMPPE), serpiginous, birdshot, multifocal choroiditis, Toxocara, POHS

Retinitis: ARN, CMV, toxoplasmosis, candidiasis, cysticercosis, onchocerciasis

Vasculitis: Eales disease

Other infections: nematodes, Whipple’s disease, EBV, Lyme disease

Other: amyloidosis, ocular ischemia, masquerade syndromes, spillover from anterior uveitis

Intermediate uveitis: pars planitis, MS


Complications


NV, CME, ON swelling and atrophy


CME: common cause of vision loss in pars planitis, birdshot retinochoroidopathy, retinal vasculitis, and any iridocyclitis (especially chronic, recurrent cases); CME does not occur in VKH


Indications for cytotoxic therapy


Behçet’s disease, sympathetic ophthalmia, VKH, pars planitis, Eales disease, retinal vasculitis, serpiginous choroidopathy, OCP, necrotizing scleritis, inflammations unresponsive to maximum steroid therapy



Infections



Toxoplasmosis


(See Ch. 5, Pediatrics/Strabismus)



Toxocariasis


(See Ch. 5, Pediatrics/Strabismus)



Presumed Ocular Histoplasmosis Syndrome (POHS)


(See Ch. 11, Posterior Segment)



Cytomegalovirus (CMV)


Progressive hemorrhagic necrotizing retinitis involving all retinal layers


Occurs in 15–46% of AIDS patients; usually when CD4 count <50 cells/mm3


40% bilateral at presentation


Rare syndrome of neonatal cytomegalic inclusion disease



Symptoms


often asymptomatic; may have floaters, scotoma



Findings


well-circumscribed necrotizing retinitis (2 appearances), mild AC and vitreous reaction


Brushfire: indolent, granular, yellow-white advancing edge with peripheral atrophic ‘burned out’ region

Pizza-pie fundus: thick, yellow-white necrosis; hemorrhage, vascular sheathing (Figure 8-6)

image

Figure 8-6 Cytomegalovirus retinitis.


(From Hudson HL, Boyer DS, Martin DF, et al: Viral posterior uveitis. In Yanoff M, Duker JS [eds]: Ophthalmology, London, Mosby, 1999.)



Pathology


infected retinal cells are markedly enlarged, then necrotic, finally atrophic; large owl’s eye intranuclear inclusions



Treatment


antiviral therapy (induction during first 2 weeks)


Ganciclovir (Cytovene): virostatic
TOXICITY: neutropenia and thrombocytopenia

INDUCTION: 5–7.5 mg/kg IV bid × 2–4 weeks

MAINTENANCE: 5–10 mg/kg IV qd

INTRAVITREAL INJECTION: 200–2000 µg/0.1 mL 2–3 times a week × 2–3 weeks

Foscarnet: virostatic
TOXICITY: renal

INDUCTION: 90 mg/kg IV bid or 60 mg/kg IV tid × 2 weeks

MAINTENANCE: 90–120 mg/kg IV qd

INTRAVITREAL INJECTION: 2.4 mg/0.1 mL 2–3 times a week × 2-3 weeks, then 1–2 times a week

Cidofovir (Vistide): longer half-life
TOXICITY: renal, uveitis (50%), hypotony

INDUCTION: 3–5 mg/kg IV once a week × 2 weeks

MAINTENANCE: 3–5 mg/kg IV once every 2 weeks

Administered through peripheral line (central line required for ganciclovir and foscarnet)

INTRAVITREAL INJECTION: 165–330 µg once a week × 3 weeks, then every 2 weeks

Associated with lowering of IOP (about 2 mmHg), 20–50% develop iritis (about 5 days after last infusion)

Probenecid and hydration with each dose to reduce renal toxicity and decrease iritis

Median time to progression = 120 days

B-scan ultrasound in patients with severe hypotony revealed CB atrophy

Ganciclovir (Vitrasert):
Median time to progression = 194 days (vs 72 days with IV ganciclovir and 15 days with no treatment)

May be increased risk of RD with implantation

Oral ganciclovir: poor bioavailability; only 6% absorbed with food, 9% absorption without food

Surgery: vitrectomy with long-acting tamponade for RD repair


Complications


rhegmatogenous RD



Acute Retinal Necrosis (ARN)


Acute self-limited confluent peripheral necrotizing retinitis due to infection with VZV, HSV, or rarely CMV


Usually occurs in immunocompetent individuals; 33% bilateral (BARN), commonly in immunosuppressed


Association with HLA-DQw7 (50%)



Symptoms


rapid onset of ocular/periocular pain, pain on eye movement, redness, photophobia, floaters, decreased vision, constriction of visual field



Findings


diffuse episcleral injection, mild iritis with granulomatous KP, vitritis; ‘thumbprint’ nummular infiltrates posterior to equator with isolated peripheral patches of necrotizing retinitis that becomes confluent; sawtooth demarcation line between necrotic and healthy retina, generalized obliterative retinal arteritis (with peripheral vaso-occlusion), pale disc edema (Figure 8-7); within 2 months, retinitis gradually resolves and necrotic retina sloughs; coarse salt and pepper pigmentation


image

Figure 8-7 Acute retinal necrosis.


(From Kaiser PK, Friedman NJ, Pineda II, R: Massachusetts Eye and Ear Infirmary Illustrated Manual of Ophthalmology, 2nd edn. Philadelphia, WB Saunders, 2004.)



Pathology


necrosis occurs from virally induced cytolysis, arteriolar and choriocapillaris occlusion; necrotic cells slough into vitreous, leaving large areas devoid of retina



FA


focal areas of choroidal hypoperfusion early; late staining



Treatment


acyclovir (IV × 5–10 days, then oral × 6 weeks; decreases risk of development of ARN in fellow eye by approximately 50%; ganciclovir is an alternative); oral steroids; aspirin to inhibit vascular thrombosis



Prognosis


watch fellow eye closely (usually develops ARN within 4 weeks)


65–90% develop rhegmatogenous RD (usually within 3 months)



Progressive Outer Retinal Necrosis (PORN)


Variant of ARN in AIDS but painless with minimal intraocular inflammation


Often have history of cutaneous zoster


74% unilateral at presentation, 70% become bilateral


Findings: multiple discrete peripheral or central areas of retinal opacification/infiltrates (deep with very rapid progression), ‘cracked mud’ appearance after resolution; vasculitis is not prominent (Figure 8-8)


image

Figure 8-8 Progressive outer retinal necrosis, early stage.


(From Hudson HL, Boyer DS, Martin DF, et al: Viral posterior uveitis. In Yanoff M, Duker JS [eds]: Ophthalmology, London, Mosby, 1999.)


Treatment: combination of foscarnet and ganciclovir; poor response to antivirals


Prognosis: 67% become NLP within 4 weeks; RD in 90%



Herpes Zoster


Uveitis typically develops during convalescence from acute Varicella infection

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  3. Pediatrics / Strabismus
  4. Neuro-ophthalmology

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Jun 4, 2016 | Posted by in OPHTHALMOLOGY | Comments Off on Uveitis

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