Viral Uveitis

Prof. Dr. Yonca

Aydın Akova

Bayındır Hastanesi Ankara

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Viral Uveitis •  Herpes simplex virus

(HSV) •  Herpes zoster virus

(VZV) •  Cytomegalovirus (CMV) •  Fuchs Uveitis

Epidemiyology •  Herpes simplex or varicella zoster

virus uveitis are responsible for 5-10% of all uveitis cases • Most common cause of anterior

infectious uveitis •  HSV uveitis may occur at any age

(children/ young adults) •  VZV uveitis in elderly/

immunocompromised patients

Pathogenesis

•  Intact virus particules in anterior chamber •  Immune reaction •  Iris stroma is infiltrated by

lymphocytic cells

Herpetic Uveitis •  Unilateral •  Recurrent attacks •  Acute ocular

hypertension •  Active/inactive

corneal involvement •  Isolated entity

Anterior Uveitis

•  1 week to several months •  Recurrences are

common •  Anterior chamber

inflammation may be mild or severe – Hypopyon – Hyphema

Keratic Precipitates •  Keratic precipitates

(KPs) are diffusely distributed on the corneal endothelium – Fine stellate Kps – Moderate/large size

mutton fat keratic precipitates

– Collect frequently under areas of active keratitis

Diffuse Large KPs

Herpetic uveitis iris atrophy

Pupillary Distorsion Dilated Pupil

High Intraocular Pressure

•  Acute increase in IOP (90%) •  İnflammation of the trabecular

meshwork •  Responds to topical

corticosteroid therapy •  Similar to the attacks of Posner-

Schlossman syndrome

Diagnosis •  Clinical findings •  Presence or hx of

herpetic dermatitis or dendritic keratitis •  Corneal stromal scars or

edema •  Decreased corneal

sensation •  Acutely elevated

intraocular pressure, or iris atrophy

Disciform Endothelitis

• Central / paracentral stromal /epithelial edema • KPs •  İritis • High IOP

Diffuse Endothelitis

•  Diffuse stromal/epithelial edema •  KPs •  Hypopyon/

retrocorneal plaque •  High IOP

Herpetic uveitis

Herpetic Uveitis & immune ring

Lineer Endothelitis

•  Lineer KPs •  Peripheral stromal and epithelial edema

Diagnosis •  The signs of herpetic eye disease can

be subtle – High degree of suspicion is important

•  Unilateral uveitis •  Elevated intraocular pressure •  Patchy or sectoral iris atrophy •  Keratic precipitates are diffusely

distributed on the corneal endothelium

Diagnosis

•  Clinical Diagnosis •  Viral culture • Quantitative multiplex real time

polymerase chain reaction (PCR) • Goldmann-Witmer coefficient •  Confocal mikroskopy

Molecular Diagnosis •  0.1 cc aqueous

humour aspirated •  Quantitative real

time PCR –  Viral DNA

genome detection •  Gold standard •  %80-96 positive

Goldmann-Witmer (GW) Coefficient

• Measuring local production of specific anti-virus antibodies (ELISA) • Goldmann-Wittmer coefficient (Q) GW = AC anti HSV Ab : AC Ig Serum anti HSV Ab Serum Ig • GW > 4 local antibody production

Confocal Microscopy

•  High amounts of Dendritic cells in the corneal subepithelial nerve plexus

Therapetic Approach •  Topical steroids – Gradual tapering – Long term/low

dose therapy

•  Topical antiviral ttheray indicated when corneal involvement present

•  Topical/systemic antiglaucomatous treatment

Systemic Antiviral Therapy Treatment Acyclovir 400 mg five times per day Valacyclovir 1000 mg twice per day Famciclovir 250 mg three times per day •  Long term low dose profilaxis may be

helpful reducing recurrences and inflammation

Prophylaxis Acyclovir 400 mg twice daily Valacyclovir 1000 mg once daily

Herpetic Eye Disease Study (HEDS)

The role of oral acyclovir in herpetic uveitis?

•  In addition to topical therapy •  Oral acyclovir vs placebo 400 mg X 5 10

weeks •  No statistical difference

HEDS Group Arch Ophthalmol 1996;114:1065-72

Herpes Zoster Uveitis

•  Usually in older patients but it may occur at any age •  History of ipsilateral zoster

dermatitis •  Pseudodendrites •  Decreased corneal sensation •  Sectoral iris atrophy

Herpes Zoster Uveitis

•  Uveitis occurs 40 % of HZO patients 1-3 weeks after the onset of skin rash •  Anterior uveitis – Recurren – Granulamatous

•  IOP rise •  Iris atrophy

Herpes Zoster Uveitis

•  Patchy iris atrophy at the iris •  Similar to herpes

simplex uveitis •  PCR

Herpes Zoster Uveitis

Granulamatous KPs

Iris atrophy

Herpes Zoster Uveitis Iris Atrophy

Differential Diagnosis

•  It is often very difficult to distinguish herpes simplex versus herpes zoster based on clinical signs alone

Differential Dignosis HSV vs VZV Anterior Uveitis

HSV •  In children/ young

adults •  Skin lesions grouped

vesicles •  Dendrites/stromal •  İris atrophy at

pupillary margin

HZV •  In elderly/

immunocompromised patients

•  Vesicles follows a dermatomal distribution

•  Pseudodendrites/stromal

•  Patchy iris atrophy

Ophthalmologic Findings of Patients with Rubella Virus- and Herpes Virus-Associated Anterior Uveitis

RV Uveitis HSV Uveitis VZV Uveitis

Conjunctival redness 6/46(13%) 23/37(62%) 4/7(57%) Corneal edema 1/55(1.8%) 20/37(54%) 3/10(30%) Previous keratitis 2/56(3.6%) 12/36(33%) 2/8(2.5%) KPs present† 47/56(84%) 29/38(76%) 7/10(70%) Cells ≥2+ 8/56(14%) 21/39(54%) 2/10(20%)

Posterior synechiae 4/55(7.3%) 14/37(38%) 4/10(40%) Heterochromia 13/56(23%) 0/37 0/10 Inflammatory cells 45/51(88%) 10/23(43%) 5/6(83%) in vitreous Wensing B Ophthalmology, 118:1905, 2011

Cytomegalovirus Anterior Uveitis

•  Newly described entity •  Immunocompetant

patient •  Unilateral uveitis/

endotheliitis •  Acute recurrent/

chronic uveitis •  IOP rise

Cytomegalovirus Uveitis/Endotheliitis

•  Focal endoteliitis (multiple coin shaped lesions) •  Diffuse endoteliitis •  Local/diffuse corneal

edema/descemet folds •  Medium sized

keratic precipitates – Ring or lineer pattern

CMV Anterior Uveitis

CMV Endothelitis

Cytomegalovirus Uveitis

•  Mild anterior chamber reaction •  Patchy or diffuse iris

atrophy + •  No posterior synechiae •  No corneal scar •  No fibrin/flare •  No posterior segment

involvement

Diffuse Corneal Edema

Differential Diagnosis •  Herpes simplex •  Herpes zoster

uveitis/keratouveitis •  Fuchs uveitis

Diagnosis •  High index of clinical

suspicion •  No response or partial

response to acylovir treatment

•  Focal endotheliitis (single/multiple coin shaped lesions)

•  Diagnostic anterior chamber tap and quantitative PCR analysis

•  Proper antiviral therapy

•  Goldmann-Witmer coefficient

When we should tap anterior chamber?

•  Frequent recurrence •  No response or partial

response to systemic acyclovir/valacylovir and steroid therapy

•  Clinical findings suggesting CMV uveitis

•  Decreased vision

Real Time PCR Diagnostic anterior chamber tap •  100 µl aqeous is aspirated with 27

gauge needle •  Stored and transported at 2-4

degrees Celsius for 24 hours •  Real time quantitative multiplex

PCR – CMV, HSV, HZV

Persistent Corneal Edema Risk Factors

•  Pretreatment severe edema 75 % •  Older age •  Previous corneal

graft •  Glaucomatous

damage •  Late diagnosis

Chee SP Graefes Clin Exp Ophthalmol 2012

Therapy •  Systemic valganciclovir –  450 mg 2x2, 6 weeks –  450 mg 2x1 3-9 month

•  Ganciclovir jel, 0.15% 4x1 6 weeks •  İntravitreal ganciclovir •  Ganciclovir implant •  Topical steroids •  Antiglaucomatous

therapy

CMV Endoteliitis/Akova •  9 patients •  Age 17- 59 •  All cases immunocompetent •  6 patients with focal endoteliitis/anterior

uveitis •  3 patients with diffuse edema •  8/9 IOP rise •  8/9 recurrent chronic inflammation •  First case 2009, last 18 months 6 cases

CMV Endoteliitis/Akova

•  In all patients anterior chamber tap and quantitative multiplex PCR for HSV, VZV, CMV, EBV were performed •  CMV was positive •  Time between referral and diagnosis

1 week - 5 years

Therapy •  7 patients received oral ganciclovir

(average 7 months), •  2 patients received additional topical

ganciclovir •  2 patients received only topical

ganciclovir •  Corneal decompensation in 2 eyes •  In 7 eyes inflammation was controlled

with mild recurrences (3 eyes)

Conclusions •  Focal or diffuse endotheliitis, and

corneal edema •  IOP rise •  Chronic and/or recurrent inflammation •  Partial or no response to acyclovir/

valacyclovir therapy – Anterior chamber tap – Multiplex real time PCR – Early diagnosis and treatment

Fuchs Uveitis •  Unilateral chronic

anterior uveitis •  Vitreous opacities •  Heterochromia •  Stellate KPs •  Diffuse iris atrophy •  No posterior synechia

Patogenesis In Fuchs Uveitis •  Intraocular evidence of rubella virus (in

European) – Rubella genome detection in aqueous – Positive GWC results

•  Intraocular evidence of CMV virus (in Asian) – CMV genome detection in aqueous – Positive GWC results Quentin CD et al, Am J Ophthalmol, 2004;138:46–54. Chee SP al Am J Ophthalmol, 2008;146 :883-9

Thank you

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yoncaakova@yahoo.com