ophthalmic manifestations of hiv infection krisada hanbunjerd
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Ophthalmic Ophthalmic manifestationsmanifestations
ofofHIV infectionHIV infection
KRISADA HANBUNJERD
ophthalmic manifestation of HIV infection
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Ophthalmic manifestations
Incidence = 44.6%* consist of Noninfectious microangiopathy Opportunistic ocular infections Neoplasm of ocular adnexa Neuroophthalmic manifestation Drug-induced manifestation*epidemiology of ocular complication of HIV infection in ChiangMai
ophthalmic manifestation of HIV infection
Noninfectious microangiopathy
Conjunctival vessel abnormalitiescapillaries dilatationisolated vascular fragmentirregular vessel calibergranular blood column
HIV retinopathy
ophthalmic manifestation of HIV infection
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HIV retinopathyoverview
most common ophthalmic lesion characterized by
cotton wool spot
retinal hemorrhage
microaneurysm
telangiectatic vessel
indicate immune deteriolation
ophthalmic manifestation of HIV infection
HIV retinopathymanifestations
Cotton Wool Spotoccur 28-92% of patient with AIDSare microinfarct of nerve fiber layer of retinaclinically white fluffy lesion with feathery bordercommon site is peripapillaresolved within 4-6 weeks
Retinal Hemorrhageoccur less than 20%
Perivascular Sheathingoccur less than 1%more common in AFRICA
ophthalmic manifestation of HIV infection
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HIV retinopathypathogenesis
multifactorial may be immune complex deposition
HIV infection of retinal vascular endotheliumlocal release of cytotoxic factorsrhealogic abnormalities such as
RBC aggregation,elevated fibrinogen level
circulating immune complex,plasma viscosity
ophthalmic manifestation of HIV infection
Differentiation
Diabetes Mellitus
Malignant Hypertension
Collagen Vascular Disease
ophthalmic manifestation of HIV infection
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Differentiation
especially from early Cytomegalovirus Retinitis
ophthalmic manifestation of HIV infection
Opportunistic ocular infections (COMMON)
Anterior segmentMicrosporidial keratoconjunctivitisHerpes zoster ophthalmicus eyelid Molluscum
contagiosum
ophthalmic manifestation of HIV infection
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Opportunistic ocular infections (COMMON)
Posterior segment
Cytomegalovirus retinitis
Varicella zoster retinitis
Toxoplasma retinitis
ophthalmic manifestation of HIV infection
Opportunistic ocular infections(UNCOMMON)
Anterior segmentBacterial keratitisHerpes simplex keratitis
Posterior segmentPneumocystic choroiditisFungal chorioretinitisOcular syphilisOcular tuberculosis
ophthalmic manifestation of HIV infection
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Cytomegalovirus Retinitis overview
The most common of opportunistic ocular infection in patient with AIDS
occur in approximately 20-40% of these patient
progressive if left untreated potentially blinding disease ultimately developed bilateral
ophthalmic manifestation of HIV infection
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Cytomegalovirus Retinitis High Risk
CD Count < 50 Associated with PCP, Extraocular
CMV ,Toxoplasmosis HLA B44 , B51 , DR7
ophthalmic manifestation of HIV infection
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Cytomegalovirus Retinitis Symptoms
asymptomatic light flash floater visual field loss blurred or distorted vision red eye,eye pain,photophobia are rare
ophthalmic manifestation of HIV infection
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Cytomegalovirus Retinitis Signs
no conjunctival hyperemia minimal anterior chamber inflammatory
reaction minimal vitreous inflammatory reaction typically yellow to white area of retinal
necrosis that follow a vascular distribution
ophthalmic manifestation of HIV infection
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Cytomegalovirus Retinitis Diagnosis
based on clinical fundus appearance
vitreous and aqueous humor analysis for CMV DNA **
endoretinal biopsy **
** for atypical presentation or unresponsive to treatment (usually not be done in normal setting)
ophthalmic manifestation of HIV infection
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Cytomegalovirus Retinitis Clinical Presentation
Spectrum of fundus appearance fulminant/edematous form indolent form frosted branch angiitis form atypical form
ophthalmic manifestation of HIV infection
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Cytomegalovirus Retinitis Clinical Presentation
Fulminant form dense confluent
area of retinal opacification location along vesseles no clear central atrophic area sufficient retinal hemorrhage inflammatory perivascular
sheathing
ophthalmic manifestation of HIV infection
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Cytomegalovirus Retinitis Clinical Presentation
Indolent form faint grainy opacification
or blush fire location not overlying vessel may have central clear
atrophic area no or minimal retinal hemorrhage no inflammatory vascular
sheathing
ophthalmic manifestation of HIV infection
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Cytomegalovirus Retinitis Clinical Presentation
Frosted branch angiitis form
usually neglected case indicate insufficient
control of disease ( practically seen in patient who lost follow up treatment)
ophthalmic manifestation of HIV infection
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Cytomegalovirus Retinitis Systemic Treatment
FDA approved IV Gancyclovir Induction and Maintenance IV Foscarnet Induction and Maintenance IV Gancyclovir Induction and Oral
Gancyclovir Maintenance IV Cidafovir Induction and Maintenance Oral valgancyclovir for Induction and
Maintenance (non zone1CMVR)
ophthalmic manifestation of HIV infection
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Cytomegalovirus Retinitis Dosage
GancyclovirIV Dosage Induction 5mg/kg
q 12 hours 14-21 days
Maintenance 5mg/kg daily or 6mg/kg 5 out of 7 days
FoscarnetIV Dosage Induction
60 mg/kg q 8 hours 14-21 days
Maintenance 90-120 mg/kg daily
ophthalmic manifestation of HIV infection
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SOCA1 234 patients with newly diagnosed CMVR
randomized to gancyclovir or foscarnet Time to progression :56 days for
gancyclovir V.S. 59 days for foscarnet (p=0.685)
Median survival 12.6 months for foscarnet V.S. 8.5 months for gancyclovir
ophthalmic manifestation of HIV infection
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SOCA1 More neutropenia with gancyclovir More infusion related symptoms
genitourinary symptoms,nephrotoxic effect and electrolyte abnormality with foscarnet
Patient with foscarnet more likely to be switched to alternative treatment (46% V.S. 11%;p<0.00)
Toxicity resolved in 88% of cases after treatment switches
ophthalmic manifestation of HIV infection
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Cytomegalovirus Retinitis Dosage
CidofovirIV Dosage Induction 5mg/kg weekly 2 weeks Maintenance 5mg/kg every 2 weeks
ophthalmic manifestation of HIV infection
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Cytomegalovirus Retinitis General Consideration of Treatment
IV Antivirals are all effective for induction and maintenance
IV Antivirals have unique complications
gancyclovir-neutropenia
foscarnet-nephrotoxic
cidofovir-nephrotoxic,uveitis,hypotony
ophthalmic manifestation of HIV infection
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Cytomegalovirus Retinitis General Consideration of Treatment(continue)
IV Treatment is associated with catheter’s complication
IV Treatment is costly IV Treatment needs hospitalization? Time consumed Systemic or Local Treatment
ophthalmic manifestation of HIV infection
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Intravitreal drugs
Gancyclovir
Foscarnet
Cidofovir
fomivirsen Gancyclovir Intraocular Implant
Cytomegalovirus Retinitis Local Treatment
ophthalmic manifestation of HIV infection
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Cytomegalovirus Retinitis Intravitreal Injection
Gancyclovir Dosage Induction :200-4000microgram 2-3times/week Maintenance: same dose weekly
Foscarnet Dosage Induction 1.2-2.4 mg 2 times/week Maintenance 1.2-2.4 mg weekly
Cidofovir Dosage 20 microgram q 5-6 weeks
ophthalmic manifestation of HIV infection
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Cytomegalovirus Retinitis Gancyclovir Implant
release drug 1 microgram/hour for 32 weeks
intravitreal drug level 4 fold higher than intravenous
median time to progress = 226 days retinal detachment 11-23% contralateral involvement 50% in 6 months
ophthalmic manifestation of HIV infection
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CYTOMEGALOVIRUS RETINITIS Local Treatment(advantages)
prevent systemic side effect need less drug so less cost improve quality of lifehigher drug concentration
ophthalmic manifestation of HIV infection
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Intraocular Gancyclovir Level
microgram/ml intravenous induction 0.78 intravenous maintenance 0.63 oral gancyclovir 0.83 implant 4 intravitreal injection(24hr) 143 intravitreal injection(72hr) 23
ophthalmic manifestation of HIV infection
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CYTOMEGALOVIRUS RETINITIS Local Treatment(disadvantages)
unability to protect contralateral eye increase risk of extraocular CMVR less survival
ophthalmic manifestation of HIV infection
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CYTOMEGALOVIRUS RETINITIS Local Treatment(complications)
increase intraocular pressure
increase risk of retinal detachment
vitreous hemorrhage endophthalmitis
scarring of injected site,retinal toxicity?
ophthalmic manifestation of HIV infection
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Role of oral Gancyclovir
Low bioavailability Cause neutropenia Not indicate for induction therapy* Suitable for maintenance therapy in higher
dose (>4500mg/day)* May be combined with IV Gancyclovir or
Gancyclovir implant*due to low intraocular gancyclovir level
ophthalmic manifestation of HIV infection
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valgancyclovir(valcyte)
is an L-valyl ester (prodrug) of ganciclovir absolute bioavailability was approximately 60% rapid conversion to ganciclovir elimination by renal excretion through glomerular
filtration and active tubular secretion.
The half-life (t1/2) of ganciclovir following oral
administration of valganciclovir tablets was 4.08 +- 0.76 hours (n=73)
ophthalmic manifestation of HIV infection
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Dosage of Valgancyclovir
Dose Modifications for Patients with Impaired Renal Function
CrCl(mL/min) Induction Dose Maintenance Dose > 60 900 mg twice daily 900 mg once daily 40 – 59 450 mg twice daily 450 mg once daily 25 – 39 450 mg once daily 450 mg every 2 days 10 – 24 450 mg every 2 days 450 mg twice weekly
ophthalmic manifestation of HIV infection
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Decrease incidence From 21.9 Per 100 Person-Year To 3.7 Per 100 Person-Year
Change in the clinical course of the disease
Altered Clinical presentation
CYTOMEGALOVIRUS RETINITISIN HAART ERA
ophthalmic manifestation of HIV infection
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CLINICAL COARSECHANGE
From Progressive if lefted untreated To Ability to discontinue AntiCMV
agent without progression
ophthalmic manifestation of HIV infection
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Source,year No of Patients Median Time(Range) No of Patients CD4 Cell Count(Range)
(NoRx) Not Receiving Therapy With Reactivation When Therapy Stopped
month 10 /L
Whitcup,1997 4(1) 6(4-12) 0 0.24-0.28
Reed,1997 4(4) 5(4-7) 0 not available
Tural,1998 7(0) 9(9-12) 0 0.18-0.52
Macdonald,1998 11(0) 5(3-18.5) 0 0.06-0.41
Vrabec,1998 8(0) 13.5(3-16) 0 0.09-0.24
Whitcup,1998 2(2) 9.5(7-12) 1 0.06-0.11
Jabs,1998 15(0) 8(3-16) 0 0.09-0.65
Whitcup,1999 14(0) 16.4(8-22) 0 0.08-1.3
Reported Cases of Inactive Cytomegalovirus Retinitis Without Specific AntiCMV Therapy
ophthalmic manifestation of HIV infection
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ALTERED CLINICAL PRESENTATIONFROM IMMUNE RESTORATION
Immune Recovery Vitritis Cystoid Macula Edema Epiretinal Membrane Vitreomacula traction syndrome Disc Edema and Neovascularization
ophthalmic manifestation of HIV infection
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IMMUNE RECOVERY UVEITIS(IRU)
3 I Intraocular inflammation characterized by
vitritis ,disc edema , cytoid macula edema usually reversible , treated by local steroid if still unchanged
Inactive cytomegalovirus retinitis Immune recovery by CD4 rise >50 longer
than 3 months
ophthalmic manifestation of HIV infection
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D/D for CMVR
Progressive Outer Retinal Necrosis Toxoplasma Retinitis Intraocular Lymphoma Ocular Syphilis
ophthalmic manifestation of HIV infection
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Progressive Outer Retinal Necrosis caused by VZV , Herpes simplex
virus , CMV minimal anterior and vitreal
inflammatory reaction start at peripheral retina first
as deep multifocal opacification then progress rapidly to
posterior pole and cause secondary retinal detachment finally
ophthalmic manifestation of HIV infection
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Toxoplasmic Retinitis usually acquired disease granulomatous anterior uveitis focal or multifocal retinitis +/- vitritis no previous toxoplasma retinochoroidal
scar approximately 50% of retinitis patient have
encephalitis (not vice verca)
ophthalmic manifestation of HIV infection
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Neoplasm of Ocular Adnexa Kaposi sarcoma
usually asymptomatic sites involved are eyelid , conjunctiva , orbitinferior fornix is most common site
non Hodkin’s lymphomanon tender anterior orbital massproptosis , diplopia , ptosis ,eyelid edema
Conjunctival squamous carcinoma
ophthalmic manifestation of HIV infection
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Neuroophthalmic Manifestations Cranial nerve palsy: CN6 palsy
Internuclear ophthalmoplegia CN 3 palsy
Visual field defects
ophthalmic manifestation of HIV infection
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Neuroophthalmic Manifestations
Optic nerve disorder
Papilledema , optic atrophy
retrobulbar optic neuritis
papillitis Cortical blindness
ophthalmic manifestation of HIV infection
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Cryptococcal Papilledema cause increase
intracranial pressure back to the eye
these picture show optic nerve head in various stage
ophthalmic manifestation of HIV infection
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Drug induced manifestations
Cidofoviranterior uveitis , hypotony ,
enopthalmos
ophthalmic manifestation of HIV infection
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Drug induced manifestations
Rifabutinanterior uveitis
Terbinafineanterior uveitis , iridodonesis
phacodonesis , conjunctival hemorrhage
ophthalmic manifestation of HIV infection
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International Variation of Manifestationsmost common reported ocular conditions
Industrialized Countries
Subsaharan Africa
Latin America
South and Southeast Asia
CMVR
HZO
conjunctival squamous cell tumors
CMVR
ocular toxoplasmosis CMVR
HZO
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