ocu hiv.ppt

Ophthalmic
Manifestations
of
HIV infection
OPH
MCK

2/5/2024 9:18 AM ophthalmic manifestation of HIV infection 2
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

Ocular findings
prevalence
 Micro-vasculopathy -(25%)
 Uveitis - (8%)
 Cytomegalovirus retinitis - (7%)
 Neuro-ophthalmic manifestations - (6%)
 Herpes zoster ophthalmicus - (5%)
 Kaposi sarcoma lid - (3%)
 Conjunctival carcinoma -(2%)
 Sub-conjunctival haemorrhage -(1%)
 Others (conjunctivitis, blepharitis, corneal ulcer) -(53%)
SOUTH AFRICAN STUDY-2004

Noninfectious microangiopathy
 Conjunctival vessel abnormalities
Capillaries dilatation
Isolated vascular fragment
Irregular vessel caliber
Granular blood column
 HIV Retinopathy

HIV retinopathy
overview
 Most common ophthalmic lesion
 Characterized by
Cotton wool spot
Retinal hemorrhage
Micro aneurysm
Telangiectatic vessel
 Indicate immune deterioration

HIV Retinopathy
manifestations
Cotton Wool Spot
Occur in 28-92% of patient with AIDS
Are micro infarct of nerve fiber layer of retina
Clinically white fluffy lesion with feathery border
Common site is peripapilla
Resolves within 4-6 weeks
Retinal Hemorrhage
Occur less than 20%
Peri vascular Sheathing
Occur less than 1%
More common in AFRICANS

HIV retinopathy
pathogenesis
 Multifactorial
 May be immune complex deposition
HIV infection of retinal vascular endothelium
Local release of cytotoxic factors.
Rhea logic abnormalities such as
RBC aggregation,elevated fibrinogen level
circulating immune complex
increase in plasma viscosity

Differentiation from retinopathy
of
 Diabetes
Mellitus
 Malignant
Hypertension
 Collagen
Vascular
Disease

Differentiation
 Especially from early
Cytomegalovirus[CMV] Retinitis

Opportunistic ocular infections
(COMMON)
 Anterior segment
Microsporidial keratoconjunctivitis
Herpes zoster ophthalmicus - Eyelid Molluscum
contagiosum

(COMMON)
 Posterior segment
Cytomegalovirus retinitis
Varicella zoster retinitis
Toxoplasma retinitis

(UNCOMMON)
 Anterior segment
Bacterial keratitis
Herpes simplex keratitis
 Posterior segment
Pneumocystic choroiditis
Fungal chorioretinitis
Ocular syphilis
Ocular tuberculosis

Cytomegalovirus Retinitis
overview
 The most common of opportunistic ocular
infection in patient with AIDS
 Occur in approximately 20-40% of these
patients
 Progressive if left untreated
 Potentially blinding disease
 Ultimately develop bilaterally

High Risk
 CD4 Count < 50
 Associated with PCP
 Extra ocular CMV
 Toxoplasmosis
 HLA B44 , B51 , DR7

Symptoms
 Asymptomatic
 Light flash
 Floaters
 Visual field loss
 Blurred or distorted vision
 Red eye,eye pain,photophobia are rare

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

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)

Clinical Presentation
Spectrum of fundus appearance
 Fulminant/edematous form
 Indolent form
 Frosted branch angiitis form
 Atypical form

Fulminant form
 Dense confluent
area of retinal opacification
 Location along vessels
 No clear central atrophic area
 Sufficient retinal hemorrhage
 Inflammatory peri vascular
sheathing

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

Frosted branch
angiitis form
 Usually neglected
case
 Indicate insufficient
control of disease
( practically seen in
patient who lost
follow up treatment)

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)

Retinal Zone

Dosage
Gancyclovir
IV Dosage
 Induction
5mg/kg q 12 hours
14-21 days
 Maintenance
5mg/kg daily or
6mg/kg 5 out of 7 days
Foscarnet
IV Dosage
 Induction
60 mg/kg *q 8 hours
14-21 days
 Maintenance
90-120 mg/kg daily

RCT
 234 patients with newly diagnosed CMVR
randomized to Group A And Group B
 Group A- Gancyclovir
 Group B- Foscarnet
 Time to progression :56 days for
gancyclovir V/S. 59 days for foscarnet
(p>0.685)
 Median survival 12.6 months for A-
foscarnet V/S. 8.5 months for B-gancyclovir

RCT
 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

Dosage
Cidofovir
IV Dosage
 Induction - 5mg/kg weekly 2 weeks
 Maintenance- 5mg/kg every 2 weeks

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

General Consideration of Treatment(continue)
 IV Treatment is associated with catheter’s
complication
 IV Treatment is costly
 IV Treatment needs hospitalization?
 Time consuming
 Systemic or Local Treatment

 Intravitreal drugs
Gancyclovir
Foscarnet
Cidofovir
fomivirsen
 Gancyclovir Intraocular Implant
Local Treatment

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/Week 5-6 weeks

Intravitreal Injection

Gancyclovir Implant

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%
 Contra lateral involvement 50% in 6
months

CYTOMEGALOVIRUS RETINITIS
Local Treatment(advantages)
 Prevent systemic side effect
 Need less drug so less cost
 Improve quality of life
 Higher drug concentration

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

Local Treatment(disadvantages)
 Inability to protect contra lateral eye
 Increase risk of extra ocular CMV
 Less survival

Local Treatment(complications)
 Increase intraocular
pressure
 Increase risk of retinal
detachment
 Vitreous hemorrhage
 Endophthalmitis
 Scarring of injected
site,retinal toxicity?

Role of oral Gancyclovir
 Low bioavailability
 Cause neutropenia
 Not indicated 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

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)

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

Comparison of Valgancyclovir
and IV,Oral Gancyclovir

 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
IN HAART ERA

CLINICAL COURSE
CHANGE
 From
Progressive if left untreated
 To
Ability to discontinue Anti CMV
agent without progression

ALTERED CLINICAL PRESENTATION
FROM IMMUNE RESTORATION
 Immune Recovery Vitritis
 Cystoid Macula Edema
 Epiretinal Membrane
 Vitreomacula traction syndrome
 Disc Edema and Neovascularization

IMMUNE RECOVERY UVEITIS(IRU)
 3 I
 Intraocular inflammation characterized by
vitritis ,disc edema , cystoid macular
edema usually reversible , treated by local
steroid if still unchanged
 Inactive cytomegalovirus retinitis
 Immune recovery by CD4cell rise >50
longer than 3 months

IMMUNE RECOVERY VITRITIS

D/D for CMVR
 Progressive Outer Retinal Necrosis
 Toxoplasma Retinitis
 Intraocular Lymphoma
 Ocular Syphilis

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

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 versa)

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

Neuro ophthalmic Manifestations
 Cranial nerve palsy: CN6 palsy
Internuclear ophthalmoplegia
CN 3 palsy
 Visual field defects

Neuro Ophthalmic Manifestations
 Optic nerve disorder
Papilledema , optic atrophy
retro bulbar optic neuritis
papillitis
 Cortical blindness

Cryptococcal Papilledema
 Cause- increase
intracranial pressure back
to the eye
 These picture show optic
nerve head in various
stage

Drug induced manifestations
 Cidofovir
anterior uveitis , hypotony , enopthalmos

Drug induced manifestations
 Rifabutin
anterior uveitis
 Terbinafine
anterior uveitis , iridodonesis
phacodonesis , conjunctival
hemorrhage

International Variation of Manifestations
most common reported ocular conditions
 Industrialized
Countries
 Sub-Saharan Africa
 Latin America
 South and Southeast
Asia
 CMVR
 HZO
conjunctival Squamous
cell tumors
 CMVR
ocular toxoplasmosis
 CMVR
HZO

Easy &Difficult
 Easy is to get a place in
someone's address book.
 Easy is to judge the mistakes
of others
 Easy is to talk without thinking
 Easy is to hurt someone who loves
us.
 Easy is to ask for forgiveness
.
 Difficult is to get a place
in someone's heart
Difficult is to recognize our
own mistakes
Difficult is to refrain
the tongue
Difficult is to heal the wound
Difficult is to forgive others

Easy and Difficult
 Easy is to set rules.
 Easy is to dream every night.
 Easy is to exult in victory.
 Easy is to enjoy life every day.
 Easy is to promise something
to someone.
 Difficult is to follow them
Difficult is to fight for a
dream
Difficult is to assume defeat
with dignity...
Difficult is to give it real
value
Difficult is to fulfill that
promise

QUESTION ?
YOUR EYE HEALTH TOO

TO CONCLUDE

an OPH MCK PRESENTATION BY
DR.P.RAJEEVAN.M.Phil.
Thanks
for
Your Attention

ocu hiv.ppt

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