Transcript Chapter 18: Conflict and Negotiation

Ophthalmic
manifestations
of
HIV infection
KRISADA HANBUNJERD
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
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Noninfectious microangiopathy
 Conjunctival vessel abnormalities
capillaries dilatation
isolated vascular fragment
irregular vessel caliber
granular blood column
 HIV retinopathy
ophthalmic manifestation of HIV infection
HIV retinopathy
overview
 most common ophthalmic lesion
 characterized by
cotton wool spot
retinal hemorrhage
microaneurysm
telangiectatic vessel
 indicate immune deteriolation
ophthalmic manifestation of HIV infection
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HIV retinopathy
manifestations
Cotton Wool Spot
occur 28-92% of patient with AIDS
are microinfarct of nerve fiber layer of retina
clinically white fluffy lesion with feathery border
common site is peripapilla
resolved within 4-6 weeks
Retinal Hemorrhage
occur less than 20%
Perivascular Sheathing
occur less than 1%
more common in AFRICA
ophthalmic manifestation of HIV infection
HIV retinopathy
pathogenesis
 multifactorial
 may be immune complex deposition
HIV infection of retinal vascular
endothelium
local release of cytotoxic factors
rhealogic abnormalities such as
RBC aggregation,elevated fibrinogen level
circulating immune complex,plasma viscosity
ophthalmic manifestation of HIV infection
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Differentiation
 Diabetes
Mellitus
 Malignant
Hypertension
 Collagen
Vascular
Disease
ophthalmic manifestation of HIV infection
Differentiation
 especially from early Cytomegalovirus
Retinitis
ophthalmic manifestation of HIV infection
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Opportunistic ocular infections
(COMMON)
 Anterior segment
Microsporidial keratoconjunctivitis
Herpes zoster ophthalmicus eyelid Molluscum
contagiosum
ophthalmic manifestation of HIV infection
Opportunistic ocular infections
(COMMON)
 Posterior segment
Cytomegalovirus retinitis
Varicella zoster retinitis
Toxoplasma retinitis
ophthalmic manifestation of HIV infection
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Opportunistic ocular infections
(UNCOMMON)
 Anterior segment
Bacterial keratitis
Herpes simplex keratitis
 Posterior segment
Pneumocystic choroiditis
Fungal chorioretinitis
Ocular syphilis
Ocular tuberculosis
ophthalmic manifestation of HIV infection
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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Retinal Zone
ophthalmic manifestation of HIV infection
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Cytomegalovirus Retinitis
Dosage
Gancyclovir
Foscarnet
IV Dosage
IV Dosage
 Induction
5mg/kg q  Induction
12 hours 14-21 days
60 mg/kg q 8 hours
 Maintenance
14-21 days
5mg/kg daily or
 Maintenance
906mg/kg 5 out of 7 days
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
Cidofovir
IV 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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Cytomegalovirus Retinitis
Local Treatment
 Intravitreal drugs
Gancyclovir
Foscarnet
Cidofovir
fomivirsen
 Gancyclovir Intraocular Implant
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
 Maintenance
1.2-2.4 mg 2 times/week
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
Intravitreal Injection
ophthalmic manifestation of HIV infection
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Cytomegalovirus Retinitis
Gancyclovir Implant
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 life
 higher 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)
> 60
40 – 59
25 – 39
10 – 24
Induction Dose
900 mg twice daily
450 mg twice daily
450 mg once daily
450 mg every 2 days
ophthalmic manifestation of HIV infection
Maintenance Dose
900 mg once daily
450 mg once daily
450 mg every 2 days
450 mg twice weekly
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Comparison of Valgancyclovir
and IV,Oral Gancyclovir
ophthalmic manifestation of HIV infection
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CYTOMEGALOVIRUS RETINITIS
IN HAART ERA
 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
ophthalmic manifestation of HIV infection
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CLINICAL COARSE
CHANGE
 From
Progressive if lefted untreated
 To
Ability to discontinue AntiCMV
agent without progression
ophthalmic manifestation of HIV infection
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Reported Cases of Inactive Cytomegalovirus Retinitis Without Specific AntiCMV Therapy
Source,year
No of Patients
Median Time(Range)
No of Patients
(NoRx)
Not Receiving Therapy
With Reactivation When Therapy Stopped
month
CD4 Cell Count(Range)
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
ophthalmic manifestation of HIV infection
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ALTERED CLINICAL PRESENTATION
FROM 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)
3I
 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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IMMUNE RECOVERY VITRITIS
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 , orbit
inferior fornix is most common site
 non Hodkin’s lymphoma
non tender anterior orbital mass
proptosis , 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
 Cidofovir
anterior uveitis , hypotony , enopthalmos
ophthalmic manifestation of HIV infection
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Drug induced manifestations
 Rifabutin
anterior uveitis
 Terbinafine
anterior uveitis , iridodonesis
phacodonesis , conjunctival
hemorrhage
ophthalmic manifestation of HIV infection
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International Variation of Manifestations
most 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
ophthalmic manifestation of HIV infection
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QUESTION
Do Not Miss Unseen Thailand
ophthalmic manifestation of HIV infection
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Thanks
for
Your Attentions