How to take care of our patients

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How to take care of our patients
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How to take care of our patients

• eye

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How to take care of our patientseye

• Adequate prevention of preventable disease
• Appropriated treatment of treatable disease

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How to prevent

• What is preventable disease
• How to detect preventable disease
• Who is responsible for detection
• Who is target group to be prevented

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CMVR is preventable disease

• Who is the high risk group for CMV retinitis
• Prevention is done by early detection
• Early detection is for early treatment
• The best way to prevent CMVR occurrence is HAART
  in timely period?

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Cytomegalovirus Retinitis High Risk

• CD Count lt 50
• The following clinical risk factors were
  significant predictors of CMV retinitis
• flashing lights or floaters (OR, 11.42 95 CI,
  3.43 to 38.01),
• cotton-wool spots (OR, 2.90 95 CI, 1.01 to
  8.29),
• previous opportunistic infections (OR, 1.81 95
  CI, 1.24 to 2.64),
• previous nonocular CMV infection (OR, 82.99
  95 CI, 6.86 to 1004.58),
• previous Mycobacterium infection (OR, 3.41 95
  CI, 0.99 to 11.85),
• homosexuality (OR, 2.83 95 CI, 1.13 to 7.12).
• HLA B44 , B51 , DR7

Clinical risk factors for cytomegalovirus
retinitis in patients with AIDS Ophthalmology.
2004 Jul111(7)1326-33.
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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
• (not be done in normal setting)

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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

Peripheral retinitis
Visual field loss at correspondent retinitis
CMVR c CRAO
CMVR c RRD
Hemorrhage involve macula
CMV papillitis
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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 Clinical Presentation

• Spectrum of fundus appearance
• Fulminant / Edematous form
• Indolent form
• Frosted Branch Angiitis form
• Atypical form
• Post Treatment
• Inactive lesion
• Reactivated lesion

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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
• after treatment

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CMV papillitis
after treatment
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Inactive CMVR (retinal scar)

• Occur after treatment
• (HAART/-intravitreal gancyclovir)

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D/D for CMVR

• HIV retinopathy
• Progressive Outer Retinal Necrosis
• Toxoplasma Retinitis
• Multiple choroiditis
• Intraocular Lymphoma
• Ocular Syphilis

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HIV retinopathy

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

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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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Toxoplasma Retinitis

• usually acquired disease
• granulomatous anterior uveitis
• focal or multifocal retinitis /- vitritis
• With or without previous toxoplasma
  retinochoroidal scar
• approximately 50 of retinitis patient
• have encephalitis
• (not vice versa)

after treatment
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Multiple Choroiditis

• This slide show cryptococcal choroiditis
• They finally gone without visual compromise

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Take a break please
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Who is responsible for detection

• Detection is diagnosis
• Diagnosis is both process and output
• What is/are input ?
• Inputs are doctor,knowledge,skill,instrument
• Doctor should be ophthalmologist,internist or
  general physician?
• The truth(answer) is out there..

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doctor

• Ophthalmologist
• Indirect ophthalmoscopy

• Non ophthalmologist
• Direct ophthalmoscopy

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direct v.s. Indirect ophthalmoscopy
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Systematic evaluation of fundus bydirect
ophthalmoscopy
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Inactive CMVR without antiCMV treatment
IVOS , Oct2000, Vol41, No.11
IVOS , Oct2000, Vol41, No.11
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When CMVR was treated

• CMVR in critical zone zone1 (posterior pole)
• is perfect indication
• VA is finger count or better
• (useful vision)
• Receive Antiretroviral treatment
• (since July 2000)

Zone1 is retinal area that risk to vision loss
Holland GN , Buhles WC Jr , Mastre B , et al. A
controlled retrospective study of gancyclovir
treatment for cytomegalovirus retinopathy use of
a standardized system for the assessment of
disease outcome. Arch Ophthalmol
19891071759-66.
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Appropriated Treatment

• For thai patients?
• For rich or poor patients?
• For urban or rural patients?
• For Cytomegalovirus retinitis is/are

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CMVR Treatment in Bamrasnaradura Institute

• Intravitreal ganciclovir is first line treatment
  option in AIDS patients
• (except comorbid extraocular cytomegalovirus
  infection such as CMV colitis, esophagitis)
• Dosage 2000 microgram in 0.02 cc every 2 weeks
• (No induction)
• Insulin syringe 29 gauge U100 type
• OPD setting
• Release pressure by AC tapping as necessary

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(No Transcript)
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FDA approved Drug for treatment Cytomegalovirus
Retinitis

• Systemic Treatment
• IV ganciclovir Induction and Maintenance
• IV Foscarnet Induction and Maintenance
• IV ganciclovir Induction and Oral ganciclovir
  Maintenance
• IV Cidafovir Induction and Maintenance
• Oral valganciclovir for Induction and Maintenance
  
• (CMVR not in zone1 )
• Local treatment
• Intravitreal fomivirsen
• ganciclovir implant

Note Intravitreal ganciclovir were not approved
by FDA
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Cytomegalovirus Retinitis Local Treatment
(available)

• Intravitreal drugs
• ganciclovir Induction 200-4000 mcg
  2-3times/week
• Maintenance same dose weekly
• Foscarnet Induction 1.2-2.4 mg twice/week
• Maintenance same dose weekly
• Cidofovir 20 mcg every 5-6 weeks
• Fomivirsen induction 330 mcg biweekly x2
• maintenance same dose monthly
• ganciclovir Intraocular Implant every 6-8 months

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How to prepare intravitreal drug
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Cytomegalovirus Retinitis Intravitreal Injection
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CYTOMEGALOVIRUS RETINITISlocal treatment

• advantages
• prevent systemic side effect
• need less drug so less cost
• improve quality of life
• higher drug concentration

• disadvantages
• Inability to protect contralateral eye
• increase risk of extraocular cmv infection
• less survival

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Intraocular ganciclovir Level

• microgram/ml
• intravenous induction 0.78
• intravenous maintenance 0.63
• oral ganciclovir 0.83
• implant 4
• intravitreal injection ( at 24hr ) 143
• intravitreal injection ( at 72hr ) 23

Morlet N,Young S,Naidoo D,Graham G,Coroneo
MT. High dose intravitreal ganciclovir injection
provides a prolonged therapeutic intraocular
concentration. Br J Ophthalmol. 199680214-216
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CYTOMEGALOVIRUS RETINITIS Local
Treatment(complications)

• increase intraocular pressure
• increase risk of retinal detachment
• vitreous hemorrhage
• scarring of injected site
• retinal toxicity?
• Endophthalmitis
• Post-surgical scleritis

After treatment
Ophthalmic Surg Lasers Imaging. 2004
May-Jun35(3)254-5.
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Rhegmatogenous retinal detachmentmay result from
tear of retinitis
NORMAL
compared to
RRD
retinal tear not shown here
left fundus of another patient
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Cytomegalovirus Retinitisin HAART era

• Decrease Incidence
  From 21.9 Per 100
  Person-Year (PY)
  To 3.7 Per 100 Person-Year
• Change in the Clinical Course of the Disease
• From Progressive if lefted untreated
• To Ability to discontinue AntiCMV agent without
  progression
• Altered Clinical Presentation

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Clinical Course Change (more)

• CMVR is still be risk factor for mortality in
  AIDS patients
• RR1.6 when CMVR presence
• RR1.9 when CMV viral load gt400 copy/ml
• Decrease rate of second eye involvement
• from 0.40 to 0.07(0.340.02)/PY
• Decrease rate of retinal detachment
• from 0.50 to 0.06(0.300.02)/PY
• Decrease rate of retinitis progression
• from 3.0 to 0.10(0.580.02)/PY

Risk factors for mortality in patients with AIDS
in the era of highly activeantiretroviral
therapy. Ophthalmology.2005 May112(5)771-9
Course of cytomegalovirus retinitis in the era
of highly active antiretroviral therapy 2.
Second eye involvement and retinal detachment.
Ophthalmology. 2004 Dec111(12)2232-9.)..
Course of cytomegalovirus retinitis in the era of
highly active antiretroviral therapy 1.
Retinitis progression. Ophthalmology. 2004
Dec111(12)2224-31
Ophthalmology.2005 May112(5)771-9
Ophthalmology. 2004 Dec111(12)2232-9.
Ophthalmology. 2004 Dec111(12)2224-31.
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Altered Clinical Presentation

• Immune Recovery Vitritis
• Cystoid Macula Edema
• Epiretinal Membrane
• Vitreomacula traction syndrome
• Disc Edema and Neovascularization
• Uveitic glaucoma
• Panuveitis
• Varicella zoster virus
• immune recovery stromal keratitis

Retina. 2004 Jun24(3)376-82. Br J
Ophthalmol 2001 ( November ) 851384 Am J
Ophthalmol. 2004 Apr137(4)636-8.
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Immune Recovery Uveitis (IRU)

• Criteria diagnosis is 3I
• Intraocular inflammation characterized by
  vitritis ,disc edema , cystoid macula edema
• Inactive cytomegalovirus retinitis
• Immune recovery by CD4 rise gt50 longer than 3
  months

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question
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???????????????

• ????? loss follow up ????? ???????????????????
  ??????????????????????????????????????????????29??
  ??98?? (29.5)
• ????????????????????????????????????????????????CD
  4 count
• ?????????????????????????????????cytomegalovirus
• ?????????????????????????????????????????
• ??????????????????????????????????????????????????
  ?

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Thank you for your attention