Transcript How to take care of our patients

How to take care of our patients
Krisada Hanbunjerd M.D.
How to take care of our patients’
eye
Krisada Hanbunjerd M.D.
How to take care of our patients’eye
• Adequate prevention of preventable disease
• Appropriated treatment of treatable disease
Krisada Hanbunjerd M.D.
How to prevent
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What is preventable disease
How to detect preventable disease
Who is responsible for detection
Who is target group to be prevented
Krisada Hanbunjerd M.D.
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?
Krisada Hanbunjerd M.D.
Cytomegalovirus Retinitis
High Risk
• CD Count < 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 Jul;111(7):1326-33.
Krisada Hanbunjerd M.D.
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)
Krisada Hanbunjerd M.D.
Cytomegalovirus Retinitis
Symptoms
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asymptomatic
light flash
floater
visual field loss
blurred or distorted vision
Peripheral retinitis
Hemorrhage involve macula
CMV papillitis
Visual field loss at
correspondent retinitis
CMVR c CRAO
CMVR c RRD
• red eye,eye pain,photophobia are rare
Krisada Hanbunjerd M.D.
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
Krisada Hanbunjerd M.D.
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
Krisada Hanbunjerd M.D.
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
Krisada Hanbunjerd M.D.
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
Krisada Hanbunjerd M.D.
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
Krisada Hanbunjerd M.D.
CMV papillitis
Krisada Hanbunjerd M.D.
Inactive CMVR (retinal scar)
• Occur after treatment
(HAART+/-intravitreal gancyclovir)
Krisada Hanbunjerd M.D.
D/D for CMVR
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HIV retinopathy
Progressive Outer Retinal Necrosis
Toxoplasma Retinitis
Multiple choroiditis
Intraocular Lymphoma
Ocular Syphilis
Krisada Hanbunjerd M.D.
HIV retinopathy
• most common ophthalmic lesion
• characterized by
cotton wool spot
retinal hemorrhage
microaneurysm
telangiectatic vessel
• indicate immune deterioration
Krisada Hanbunjerd M.D.
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
Krisada Hanbunjerd M.D.
Toxoplasma Retinitis
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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)
Krisada Hanbunjerd M.D.
Multiple Choroiditis
• This slide show cryptococcal choroiditis
• They finally gone without visual compromise
Krisada Hanbunjerd M.D.
Take a break please
Krisada Hanbunjerd M.D.
Who is responsible for detection
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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…..
Krisada Hanbunjerd M.D.
doctor
• Ophthalmologist
• Non ophthalmologist
• Indirect ophthalmoscopy • Direct ophthalmoscopy
Krisada Hanbunjerd M.D.
direct v.s. Indirect ophthalmoscopy
Krisada Hanbunjerd M.D.
Systematic evaluation of fundus by
direct ophthalmoscopy
Krisada Hanbunjerd M.D.
Inactive CMVR without antiCMV treatment*
Reported Cases of Inactive Cytomegalovirus Retinitis Without Specific AntiCMV Therapy
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
*IVOS , Oct2000, Vol41, No.11
*IVOS , Oct2000, Vol41, No.11
Krisada Hanbunjerd M.D.
When CMVR was treated
• CMVR in critical zone =
Zone1 is retinal area that risk to vision loss
zone1 (posterior pole)
is perfect indication
• VA is finger count or better
(useful vision)
• Receive Antiretroviral
treatment
(since July 2000)
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 1989;107:1759-66.
Krisada Hanbunjerd M.D.
Appropriated Treatment
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For thai patients?
For rich or poor patients?
For urban or rural patients?
For Cytomegalovirus retinitis is/are………………
Krisada Hanbunjerd M.D.
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
Krisada Hanbunjerd M.D.
HIV infected
Person with or
Without visual
symptoms
Complete eye
examination
Suspected
Cytomegalovirus
retnitis
Active
Cytomegalovirus
retinitis
Serial follow up
Other conditions
No
Useful vision
No
Supportive
treatment
Yes
Yes
Treatment with
Intravitreal
gancyclovir
Relapse
retinitis
Yes
Receive
HAART
Follow up
Complete
eye
examination
q 2wks
No
partial
Follow up
Complete eye
examination q 4wks
Advice to
Response to
treatment
Follow up
Complete
eye
examination
q 2wksx2
complete
Continuous
inactive lesion
No
Yes
Continue
Intravitreal
treatment
< 100
no or Virus detectable
Monitor CD4count
Available viral
load
Consider
Discontinue
Intravitreal
gancyclovir
≥100
Yes and virus undetectable
Krisada Hanbunjerd M.D.
FDA approved Drug for treatment
Cytomegalovirus Retinitis
Systemic Treatment
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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
Krisada Hanbunjerd M.D.
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
Krisada Hanbunjerd M.D.
How to prepare intravitreal drug
Krisada Hanbunjerd M.D.
Cytomegalovirus Retinitis
Intravitreal Injection
Krisada Hanbunjerd M.D.
CYTOMEGALOVIRUS RETINITIS
local 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
Krisada Hanbunjerd M.D.
Intraocular ganciclovir Level
microgram/ml
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intravenous induction
intravenous maintenance
oral ganciclovir
implant
intravitreal injection ( at 24hr )
intravitreal injection ( at 72hr )
0.78
0.63
0.83
4
143*
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. 1996;80:214-216
Krisada Hanbunjerd M.D.
CYTOMEGALOVIRUS RETINITIS
Local Treatment(complications)
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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-Jun;35(3):254-5.
Krisada Hanbunjerd M.D.
Rhegmatogenous retinal detachment
may result from tear of retinitis
Krisada Hanbunjerd M.D.
Cytomegalovirus Retinitis
in 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
Krisada Hanbunjerd M.D.
Clinical Course Change (more)
• CMVR is still be risk factor for mortality in AIDS
patients*
: RR=1.6 when CMVR presence
: RR=1.9 when CMV viral load >400 copy/ml
• Decrease rate of second eye involvement **
from 0.40 to 0.07(0.34:0.02)/PY
• Decrease rate of retinal detachment**
from 0.50 to 0.06(0.30:0.02)/PY
• Decrease rate of retinitis progression***
from 3.0 to 0.10(0.58:0.02)/PY
*Risk factors for mortality in patients with AIDS in the era of highly activeantiretroviral therapy. Ophthalmology.2005 May;112(5):771-9
**Course of cytomegalovirus retinitis in the era of highly active antiretroviral therapy: 2. Second eye involvement and retinal detachment.
Ophthalmology. 2004 Dec;111(12):2232-9.)..
*** Course of cytomegalovirus retinitis in the era of highly active
antiretroviral therapy: 1. Retinitis
progression. Ophthalmology. 2004 Dec;111(12):2224-31
*Ophthalmology.2005
May;112(5):771-9
**Ophthalmology. 2004 Dec;111(12):2232-9.
***Ophthalmology. 2004 Dec;111(12):2224-31.
Krisada Hanbunjerd M.D.
Altered Clinical Presentation
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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 Jun;24(3):376-82.
**Br J Ophthalmol 2001 ( November ) ; 85:1384
***Am J Ophthalmol. 2004 Apr;137(4):636-8.
Krisada Hanbunjerd M.D.
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 >50 longer than
3 months
Krisada Hanbunjerd M.D.
question
Krisada Hanbunjerd M.D.
ปัญหาและอุปสรรค
• คนใข้ loss follow up เพราะ ไม่มีเงินค่ าเดินทาง จากการเก็บ
รวบรวมข้ อมูลวิจยั สถาบันบาราศนราดูรพบ29คนใน98คน (29.5%)
• คนใข้ ฉีดยาเข้ าตาเกินความจาเป็ นเพราะไม่มีเงินตรวจCD4 count
• คนใข้ ไม่มีคนรักษาโรคจอตาอักเสบจากcytomegalovirus
• หมอใช้ เวลากับคนใข้ น้อยเกินไปเพราะคนใข้ มาก
• หมอสงสัยว่าทาไมต้ องเป็ นฉันเท่านันที
้ ่รักษาโรคพวกนี ้
Krisada Hanbunjerd M.D.
Thank you for your attention
Krisada Hanbunjerd M.D.