Viral Uveitis
Prof. Dr. Yonca
Aydın Akova
Bayındır Hastanesi Ankara
Financial Disclosure
Alcon
Thea
Allergan
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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