herpetische uveitis anterior - saoo€¦ · • vzv-uveitis: history of ipsilateral zoster...

SAoO-Kongress 28.2.2018

Herpetische Uveitis

FEBO-Kurs

Prof. Dr. Matthias Becker

Seite 1

SAoO-Kongress 28.2.2018Seite 2

Which one of the following concerning necrotizingherpetic retinitis (acute retinal necrosis) is false?

1. Anterior segment inflammation is variable.2. Posterior segment inflammation is generally heavy.3. The periphery of the retina is affected earlier and

more severely than the posterior pole.4. Retinal detachment occurs in up to three-quarters of

cases.5. Like other viral retinitides, affected patients are

usually immunosuppressed.


Each of the following statements is true aboutvalacyclovir except:

1. Valacyclovir acts as a “prodrug” because it isconverted into acyclovir in the small intestine andliver.

2. Oral valacyclovir is substantially more bioavailablethan oral acyclovir.

3. Valacyclovir may reduce the incidence of postherpeticneuralgia, if given within 72 hours of onset ofsymptoms.

4. Although a typical regimen for herpes zoster may beless expensive than acyclovir, the standard dosing ofvalacyclovir is more frequent than that for acyclovir.

5. Concurrent use of cimetidine can increase plasmaconcentrations of the active drug.


Cytomegalovirus (CMV) retinitis is the most commonocular manifestation of human immunodeficiencyvirus (HIV) infection.

1. TRUE2. FALSE


In Übergängen denken…

Seite 5


Herpesviridae

• Large family of DNA viruses (>130 herpesviruses) • Large double-stranded, linear DNA genomes• At least five species of Herpesviridae are extremely

widespread among humans• More than 90% of adults have been infected with at

least one of these• Latent form of the virus remains in most people

Seite 6


Herpesvirus types

Herpesvirus types known to infect humans:1. Herpes simplex virus 1 (HSV-1)2. Herpes simplex virus 2 (HSV-2)3. Varicella-zoster virus (VZV)4. Epstein–Barr virus (EBV)5. Cytomegalovirus (CMV)6. Human herpesvirus 6A (HHV-6A)7. Human herpesvirus 6B (HHV-6B)8. Human herpesvirus 7 (HHV-7)9. Kaposi's sarcoma-associated herpesvirus (KSHV)

Seite 7

Herpetic anterior Uveitis

Seite 8


Zoster ophthalmicus• Vesicles on the tip or

the side of the nose• Hutchinson sign• Precedes the

development ofuveitis

• Nasociliary branch ofN. V. innervatesboth: cornea, lateral dorsum of the nose

Seite 9

Courtesy of D. Goldstein, BCSC


Clinical signs (VZV, HSV)

• VZV-uveitis: history of ipsilateral zoster ophthalmicus• Varicella-zoster sine herpete: anterior uveitis without prior

cutaneous component• Variable corneal involvemet (keratouveitis) • Decreased corneal sensation (diffuse or localized)• Anterior, posterior synechiae• Hypopyon (hemorrhagic)

Seite 10


Übersicht Endothel-Präzipitate

Granulomatös („speckig“)• Sarkoidose, Tuberkulose, MS (beidseitig)• Herpetische Uveitis (einseitig)

Nicht-granulomatös• Fein

• Ankylosierende Spondylitis, HLA-B27+ AAU• Sternförmig-diffus

• Fuchs Uveitis Syndrom


DD: Präzipitate - granulomatös


DD: Nicht-granulomatös / fein


DD: Nicht-granulomatös/ sternförmig


Keratic precipitates

Seite 15

• Large, central greasy• Fine stellate, diffusely

distributed


Iris atrophy

• Patchy or sectoral• Pupil dilated

Seite 16

Atrophy of irispigment epitheliumnot just anteriorstroma


Ocular hypertension

• Trabeculitis• Frequent complication (DD: toxoplasmosis)• Other uveitides: decreased IOP (ciliary body

hyposecretion)

Seite 17


Clinical signs (CMV)

• Immunocompetent adults• Chronic or recurrent, unilateral, anterior uveitis, mild

AC activity• Ocular hypertension• Corneal edema• Variable degrees of sectoral iris atrophy• No corneal scars, no posterior synechiae, no flare or

fibrin and no posterior segment involvement

Seite 18


CMV

• Fails to respond to corticosteroids and high doses ofacyclovir

• Can present as acute relapsing hypertensive anterioruveitis, also known as Posner-Schlossman syndrome(PSS); half of all presumed cases of PSS are CMV-positive

Seite 19


Epstein-Barr Virus

• Associated with infectious mononucleosis (IM), Burkittlymphoma, nasopharyngeal carcinoma, Hodgkin disease, and Sjögren syndrome

• Primary infection in the context of IM: mild, self-limitingfollicular conjunctivitis

• Most ocular disease is self-limiting and does not require treatment

• Topical corticosteroids and cycloplegia

Seite 20


Diagnostic options

• Aqueous tap• Real-time PCR analysis• Goldmann-Witmer coeffizient

Seite 21


Therapeutic management: Topical

• Corticosteroids• Cycloplegics• Antiviral drugs (Zovirax) for keratouveitis (to prevent

dendritic keratitis as a complication of topicalcorticosteroid therapy)

• Prolonged topical antiviral therapy is associated with thedevelopment of keratopathy

Seite 22


Therapeutic management: Systemic

HSV or VZV (higher doses) :• Acyclovir (Zovirax, 400– 800 mg, 5 times/day)• Valacyclovir (Valtrex, 500 mg to 1 g, 2 times/day)• Famciclovir (Famvir, 250–500 mg, 3 times/day)

Seite 23


Prophylactic therapy

HSV: • Acyclovir, 400 mg 2 times/day• Valacyclovir, 500 mg/day

VZV • Acyclovir, 800 mg 2 times/day• Valacyclovir, 1 g/day

Immunization• VZV (Zostavax)

Seite 24


Take home message

• Diagnosis often made clinically• Viable therapeutic options available• Role of corticosteroids• Sometimes long-term therapy necessary

Seite 25

Herpetic posterior Uveitis


Clinical manifestations

• Viral retinitis• Spectrum of necrotizing herpetic retinopathies

• Vasculitis• Anterior segment ischemia• Retinal artery occlusion• Scleritis• Vasculitis in the orbit: cranial nerve palsies

Seite 27


Necrotizing herpetic retinopathies

• Spectrum• Rapidly progressing• Clinical picture depends upon host’s immune status:

• Immunocompetent:• Peripheral necrotizing retinitis accompanied by vasculitis, iridocyclitis,

and vitritis (ARN) • Immunocompromised:

• Necrotizing retinitis, may rapidly involve the macula + peripheral retina• without significant intraocular inflammation or vasculopathy (PORN)

Seite 28


Acute Retinal Necrosis (ARN)

• Immunocompetent patients• Most common cause of ARN syndrome is VZV, followed

by HSV-1, HSV-2, and rarely CMV• Patients with ARN due to HSV-1 and VZV tend to be

older, while those with HSV-2 tend to be younger

Seite 29

Van Gelder RN, Willig JL, Holland GN, et al. Ophthalmology. 2001;108:869


Diagnostic criteria (ARN)American Uveitis Society (AUS) criteria• Single or multiple areas of retinal necrosis with distinct borders• Necrotic foci usually located in peripheral retina• Rapid disease progression if antiherpetic treatment not instituted• Extension of foci of retinal necrosis in a circumferential fashion• Presence of occlusive vasculopathy with arteriolar involvement• Prominent anterior chamber and vitreous inflammation• Characteristics that support but are not required for diagnosis: Optic

neuropathy or atrophy, scleritis, pain

Seite 30

Holland GN Am J Ophthalmol. 1994;117:663


http://eyewiki.aao.org/Acute_retinal_necrosis


DD ARNFAST• Progressive outer retinal

necrosis (PORN)• CMV retinitis• Atypical toxoplasmosis• Acute multifocal hemorrhagic

retinal vasculitis• Bacterial/Fungal retinitis or

endophthalmitis• Autoimmune retinal vasculitis• Behc ̧et‘s disease• Commotio retinae• Central or branch retinal artery

occlusion

Seite 33

SLOW• Syphilis• Intraocular lymphoma or

leukemia• Sarcoidosis• Sympathetic ophthalmia• Vogt-Koyanagi-Harada

syndrome• Collagen-vascular disease• Retinoblastoma• Ocular ischemic syndrome


Progressive outer retinal necrosis(PORN)

• Morphologic variant of acute necrotizing herpetic retinitis, profoundly immunosuppressed

• Most often in advanced AIDS (CD4+ T lymphocytes ≤50 cells/μL)

• VZV infection most common cause• Posterior pole may be involved early in the course of the

disease, vitreous inflammatory cells are typically absent, and the retinal vasculature is minimally involved, at least initially

• PORN in HIV: history of cutaneous zoster (67%) andeventually incur bilateral involvement (71%)

Seite 34


PORN

• Similarly high rate (70%) of retinal detachment as in ARN • 2/3 final visual acuity of no light perception• Often resistant to treatment with intravenous acyclovir

alone, successful with combination systemic andintraocular therapy using foscarnet and ganciclovir

Seite 35


Cytomegalo-Virus (CMV) Retinitis

• Human immunodeficiency virus (HIV) retinopathy isthe most common ocular manifestation of patients withacquired immunodeficiency syndrome (AIDS), and occursin 50% of cases.

• Most common viral manifestation of both congenital CMV infection and of CMV as an opportunistic coinfection in HIV/AIDS

• Combination antiretroviral regimens (HAART) resultednot only in a significant decline in HIV/AIDS–associatedmortality, but also in an 80% decline in new cases per year of CMV retinitis and its complications

• 3 distinct variants:

Seite 36


CMV Type 1: Classic or Fulminant• Large areas of retinal hemorrhage against a background

of whitened, edematous, or necrotic retina• Typically appears in the posterior pole, from the disc to

the vascular arcades, in the distribution of the nerve fiberlayer, and associated with blood vessels

Seite 37


CMV Type 2: Granular or Indolent

• Retinal periphery• Little or no retinal edema, hemorrhage, or vascular

sheathing• With active retinitis progressing from the borders of the

lesion

Seite 38

Courtesy of C. LowderBCSC


CMV Type 3: Perivascular

• Variant of “frosted-branch” angiitis

Seite 39

Courtesy of A Vitale BCSC


CMV ARN• Immunocompromised• Posterior pole along

vessels• Hemorrhage (pizza pie)• No vitritis• Periphlebitis• Valganciclovir, ganciclovir

Seite 40

• Immunocompetent• Initially peripheral, later

posterior pole• Hemorrhage less severe• Severe vitritis• Occlusive arteriolitis• Valaciclovir, aciclovir


EBV-induced posterior uveitis

• Isolated optic disc edema and optic neuritis• Macular edema• Retinal hemorrhages• Retinitis• Punctate outer retinitis• Choroiditis• Multifocal choroiditis and panuveitis (MCP)• Pars planitis and vitritis• Progressive subretinal fibrosis• Secondary choroidal neovascularization (CNV)

Seite 41


Intraocular fluid / tissue analysis

• Aqueous tap• Diagnostic vitrectomy• Retinal biopsy

Seite 42


Polymerase chain reaction (PCR)

• May detect minute quantities of herpetic DNA• Most sensitive, specific, and rapid diagnostic method• Vitreous an aqueous samples• Has largely supplanted viral culture, intraocular antibody

titers, and serology• Quantitative PCR-based tests may provide additional

information• viral load• disease activity• response to therapy

Seite 43


Goldmann-Witmer (GW) coefficient

• Ratio > 3 is diagnostic of local antibody production to a specific microbial pathogen

• Adjunct to the diagnosis of HSV and VZV uveitis• Little value for CMV retinitis• Combining GW coefficient with PCR analysis

Seite 44


Medical ManagementThe goals of treatment of ARN 1. Stop the retinal necrosis in order to avoid the late

consequences of the disease (retinal detachment andoptic atrophy)

2. Minimize the collateral damage caused by severeinflammation and vascular occlusions

3. Protect the fellow eye (second eye involvement 3-35%, usually within 6 weeks of disease onset, BARN)

Antiviral therapy should begin immediately after theclinical diagnosis is made, rather than waiting for

results of laboratory testing!Seite 45


General therapeutic considerations• Initiation of oral antiviral therapy at the onset of uveitis• Prolonged corticosteroid therapy with very gradual

tapering• Topical corticosteroids: very long-term, albeit extremely

low doses (1 drop per week)• Prednisone (0.5-2.0 mg/kg/day orally for up to 6-8

weeks) initiated 24-48 hours after the start of antiviral therapy or once regression of retinal necrosis beendemonstrated

• Long-term, suppressive, low-dose antiviral therapy maybe indicated

• Aspirin may minimize vascular thrombosis andpropagation of further retinal ischemia and necrosis

Seite 46


HSV and VZV1. Intravenous acyclovir, 10 mg/kg every 8 hours for 10–

14 days (check serum creatinine and liver enzymes)2. After 24–48 hours systemic corticosteroids (prednisone,

1 mg/kg/day) are introduced to treat active inflammationand are subsequently tapered over several weeks

3. Acyclovir at 800 mg orally 5 times daily, Valacyclovirat 1 g orally 2-3 times daily, or famciclovir at 500 mg orally 3 times daily should be continued for 3 months(HSV oral dose is one-half of that for VZV)

4. Extended antiviral therapy may reduce the incidenceof contralateral disease or bilateral ARN by 80% over 1 year.

Seite 47


Medical management: CMV

• Intravenous• Ganciclovir (Cymevene®, 5 mg/kg twice daily) • Foscarnet (Foscavir®, 90 mg/kg twice daily) for 2

weeks• Low-dose daily maintenance therapy or oral

valganciclovir (900 mg twice daily) for 3 weeks• Maintenance therapy (900 mg/day)

Seite 48


Antiviral agents intravitreally

Especially if retinitis (HSV, VZV, CMV) is threatening themacula or optic disc:

• Ganciclovir (Cymevene®, 200 - 2000 µg per 0.1 ml)• Foscarnet (Foscavir®, 1.2 - 2.4 mg per 0.1 ml)

Seite 49


Therapy EBV

• Systemic corticosteroids• Efficacy of systemic antiviral therapy for EBV infection

has not been established

Seite 50


Surgical Management

• Large retinal breaks frequently develop in areas of retinalnecrosis

• Tractional–rhegmatogenous retinal detachment in 50-75% of patients with ARN

• Exudative retinal detachment may arise with severeinflammation

• Prophylactic laser photocoagulation• posterior to the area of retinitis• 360°-barrier retinal photocoagulation delay laser until retinal

detachment necessitates surgery• Prophylactic vitrectomy, esp. when PVD occurs• Vitrectomy, endolaser, silicon oil

Seite 51


ComplicationsMany cases finally have less than 20/200 due to

• Vitreous hemorrhage• Retinal holes and tears• Retinal detachment• Macular pucker• Proliferative vitreoretinopathy (PVR) • Optic neuropathy• Encephalitis, dementia

Untreated, ca. 2/3 final V/A of 20/200 or worseTreated, ca. ½ final V/A of 20/40 or better; 92% better than20/400

Seite 52


Take Home Message

• Outcomes of posterior entities may be devastating• Prognosis for patients with severe immune dysfunction

remains guarded• Early diagnosis and treatment remains the key to

successful management

Seite 53


Which one of the following concerning necrotizingherpetic retinitis (acute retinal necrosis) is false?

1. Anterior segment inflammation is variable.2. Posterior segment inflammation is generally heavy.3. The periphery of the retina is affected earlier and

more severely than the posterior pole.4. Retinal detachment occurs in up to three-quarters of

cases.5. Like other viral retinitides, affected patients are

usually immunosuppressed.


Each of the following statements is true aboutvalacyclovir except:

1. Valacyclovir acts as a “prodrug” because it isconverted into acyclovir in the small intestine andliver.

2. Oral valacyclovir is substantially more bioavailablethan oral acyclovir.

3. Valacyclovir may reduce the incidence of postherpeticneuralgia, if given within 72 hours of onset ofsymptoms.

4. Although a typical regimen for herpes zoster may beless expensive than acyclovir, the standard dosing ofvalacyclovir is more frequent than that for acyclovir.

5. Concurrent use of cimetidine can increase plasmaconcentrations of the active drug.


Cytomegalovirus (CMV) retinitis is the most commonocular manifestation of human immunodeficiencyvirus (HIV) infection.

1. TRUE2. FALSE


Thank you!

herpetische uveitis anterior - saoo€¦ · • vzv-uveitis: history of ipsilateral zoster...

Documents