Ophthalmic manifestations of HIV infection

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Ophthalmic manifestationsofHIV infection

• KRISADA HANBUNJERD

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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

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Noninfectious microangiopathy

• Conjunctival vessel abnormalities
• capillaries dilatation
• isolated vascular fragment
• irregular vessel caliber
• granular blood column
• HIV retinopathy

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HIV retinopathyoverview

• most common ophthalmic lesion
• characterized by
• cotton wool spot
• retinal hemorrhage
• microaneurysm
• telangiectatic vessel
• indicate immune deteriolation

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HIV retinopathymanifestations
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
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HIV retinopathypathogenesis

• 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

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Differentiation

• Diabetes Mellitus
• Malignant Hypertension
• Collagen Vascular Disease

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Differentiation

• especially from early Cytomegalovirus Retinitis

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Opportunistic ocular infections (COMMON)

• Anterior segment
• Microsporidial keratoconjunctivitis
• Herpes zoster ophthalmicus eyelid Molluscum
  contagiosum

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Opportunistic ocular infections (COMMON)

• Posterior segment
• Cytomegalovirus retinitis
• Varicella zoster retinitis
• Toxoplasma retinitis

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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

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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

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Cytomegalovirus Retinitis High Risk

• CD Count lt 50
• Associated with PCP, Extraocular CMV
  ,Toxoplasmosis
• HLA B44 , B51 , DR7

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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

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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

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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)

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Cytomegalovirus Retinitis Clinical Presentation

• Spectrum of fundus appearance
• fulminant/edematous form
• indolent form
• frosted branch angiitis form
• atypical form

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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

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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

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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)

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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)

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Retinal Zone
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Cytomegalovirus Retinitis 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

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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 (p0.685)
• Median survival 12.6 months for foscarnet V.S.
  8.5 months for gancyclovir

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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.
  11plt0.00)
• Toxicity resolved in 88 of cases after treatment
  switches

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Cytomegalovirus Retinitis Dosage

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

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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

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Cytomegalovirus Retinitis General Consideration
of Treatment(continue)

• IV Treatment is associated with catheters
  complication
• IV Treatment is costly
• IV Treatment needs hospitalization?
• Time consumed
• Systemic or Local Treatment

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Cytomegalovirus Retinitis Local Treatment

• Intravitreal drugs
• Gancyclovir
• Foscarnet
• Cidofovir
• fomivirsen
• Gancyclovir Intraocular Implant

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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

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Cytomegalovirus Retinitis Intravitreal Injection
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Cytomegalovirus Retinitis Gancyclovir Implant
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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

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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

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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

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CYTOMEGALOVIRUS RETINITIS Local
Treatment(disadvantages)

• unability to protect contralateral eye
• increase risk of extraocular CMVR
• less survival

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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?

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Role of oral Gancyclovir

• Low bioavailability
• Cause neutropenia
• Not indicate for induction therapy
• Suitable for maintenance therapy in higher dose
  (gt4500mg/day)
• May be combined with IV Gancyclovir or
  Gancyclovir implant
• due to low intraocular gancyclovir level

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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 (n73)

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Dosage of Valgancyclovir

• Dose Modifications for Patients with Impaired
  Renal Function
• CrCl(mL/min) Induction Dose Maintenance Dose
• gt 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

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Comparison of Valgancyclovir and IV,Oral
Gancyclovir
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CYTOMEGALOVIRUS RETINITISIN 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

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CLINICAL COARSECHANGE

• From
• Progressive if lefted untreated
• To
• Ability to discontinue AntiCMV agent without
  progression

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ALTERED CLINICAL PRESENTATIONFROM IMMUNE
RESTORATION

• Immune Recovery Vitritis
• Cystoid Macula Edema
• Epiretinal Membrane
• Vitreomacula traction syndrome
• Disc Edema and Neovascularization

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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 gt50 longer than 3
  months

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IMMUNE RECOVERY VITRITIS
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D/D for CMVR

• Progressive Outer Retinal Necrosis
• Toxoplasma Retinitis
• Intraocular Lymphoma
• Ocular Syphilis

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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

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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)

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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 Hodkins lymphoma
• non tender anterior orbital mass
• proptosis , diplopia , ptosis ,
• eyelid edema
• Conjunctival squamous carcinoma

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Neuroophthalmic Manifestations

• Cranial nerve palsy CN6 palsy
• Internuclear ophthalmoplegia
• CN 3 palsy
• Visual field defects

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Neuroophthalmic Manifestations

• Optic nerve disorder
• Papilledema , optic atrophy
• retrobulbar optic neuritis
• papillitis
• Cortical blindness

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Cryptococcal Papilledema

• cause increase intracranial pressure back to the
  eye
• these picture show optic nerve head in various
  stage

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Drug induced manifestations

• Cidofovir
• anterior uveitis , hypotony , enopthalmos

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Drug induced manifestations

• Rifabutin
• anterior uveitis
• Terbinafine
• anterior uveitis , iridodonesis phacodonesis
  , conjunctival hemorrhage

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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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QUESTION
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