CYTOMEGALOVIRUS

RETINITIS
Lukman Edwar

Ocular Infection and Immunology Division

Department of Ophthalmology
Faculty of Medicine Universitas Indonesia – Cipto Mangunkusumo Hospital

Presented in INOIIS Meeting, Bali, 2012

FACTS ABOUT CMV

CMV is one of the herpes

viruses and one of the
largest human viruses and
encodes more than 200
proteins
In HIV patients with severe
immunocompromised,
reactivation of CMV may
cause some end organ
disease
EPIDEMIOLOGY

Before the epidemic of AIDS

very rare of CMV retinitis had
been reported in the medical
literature
immunocompromised
patients including organ
transplant recipients and
newborn with cytomegalic
inclusion disease

Holland. Am J Ophthalmol 2008;145:397–408

EPIDEMIOLOGY
Before introduction of HAART
CMV retinitis affected 30-
40% of HIV-infected
patients, with primarily
involved the posterior
segment of retina and
retinal detachment
After HAART
CMVR decreased to be ∼
10% of HIV-infected
Holland. Am J Ophthalmol 2008;145:397–408
OCULAR HIV - RSCM (2005-
2009)
RISK FACTORS

The value of the CD4 T-cell count of predicting the

occurrence of CMV disease is now established.
The results of studies by Gallant et al (1992), the risk of
developing CMV disease significantly higher for patients
with CD4 T-cell counts of <100 cells/mm3.
This risk varies from 5% to 11% at 6 months and increases
significantly, 13% to 15% when CD4 T-cell count decreases
to <50 cells/mm3.

Gallant et al. The Journal of Infectious Diseases 1992;166:1223-7

CLINICAL MANIFESTATIONS

Patients may complain of minor

visual symptoms such as
floaters,
flashing lights or
mild blurred vision,
visual field defect, or
Male, 43 years old, IDU (+)
VA 6/7.5 be totally asymptomatic

Jabs DA. Am J Ophthalmol 2011;151:198–216.

FUNDUSCOPY

It is recommended using indirect ophthalmoscope

Clinical signs
Fulminant type
Granular type
Frosted branch angiitis
Mixed type
FULMINANT TYPE

haemorrhagic retinal necrosis

“pizza like appearance” or
“tomato sauce on cottage cheese”
GRANULAR TYPE
FROSTED BRANCH ANGIITIS
TREATMENT

Should be early
Before whole retina / macula is affected
Permanent damage / blindness (2 mos)
Systemic treatment has the advantage of treating infection
elsewhere in the body as well as the other eye but has the
disadvantages of systemic side effects
ANTI-CMV

FDA has approved 5 anti-CMV drugs

Ganciclovir (available in Indonesia)

Foscarnet
Cidofovir
Fomivirisen

Valganciclovir (available in Indonesia)

Jacobson MA. Lancet 1997; 349: 1443–45

INTRAVITREAL GANCICLOVIR

CMV retinitis (fulminant type) with hemorrhagic retinitis

after 12th ganciclovir intravitreal injection
INTRAVITREAL GANCICLOVIR

CMV retinitis (frosted branch angiitis type)

after 8th ganciclovir intravitreal injection
INTRAVITREAL GANCICLOVIR

dosage
Initial (2-3 weeks), 2 mg/ 0.05 ml twice a week
Maintenance, 2 mg/ 0.05 ml a week
price, Rp. 900.000/vial
no evidence of systemic absorption
complication due to repeated injection
endophthalmitis
haemorrhage
retinal detachment
RSCM EXPERIENCE
CMVR TREATMENT (2005-2009)

Mean CD4 T-lymphocyte count in CMV retinitis patients

was 27.77 cells/μl (range 0-91 cells/μl)
Intravitreal ganciclovir injection was given to 34 patients
(41 eyes)
Patients were collected every Tuesday and Friday
RSCM EXPERIENCE
CMVR TREATMENT (2005-2009)

Ocular Infection and Immunology Outpatient Clinic Data, 2005 - 2009

WHEN DO WE STOP?

Discontinuation of maintenance therapy in patient with

quiescent CMV retinitis may be considered with HAART-
induced elevated CD4+ counts above 100 cells/µl
Close observation for evidence of recurrent retinitis is
indicated or immune recovery uveitis
QUIESCENT RETINA
Quiescent CMV Retinitis is defined as:
Retinal pigment epithelium (RPE) changes
Chorioretinal atrophy, without retinal whitening or
border opacification, in a region of previously active
CMVR
IMMUNE RECOVERY UVEITIS

a condition in which heightened intraocular

inflammatory reactions,
attributable to the improved immune function associated
with new potent antiretroviral therapies,
occurs in some patients with preexisting cytomegalovirus
retinitis

French et al. AIDS 2004, 18:1615–1627

Gallant et al. Optom Vis Sci 2011;88:E344–E351
RSCM EXPERIENCE

IRU developed in 2 patients

male, 37 years old, VA improved from 1/60 to 6/7.5,
injection stopped after CD 160 cells/μl. Three months
later, VA dropped to 1/60 with epiretinal membrane
and exudative RD. Patient was operated (vitrectomy)
male, 26 years old, with vitreous haze and retinal
detachment, because of very poor visual function, no
further treatment
CMV encephalitis developed in 1 patients after intravitreal
ganciclovir
DIFFERENTIAL DIAGNOSIS

Clinical signs similar with CMVR

Atypical retinochoroiditis toxoplasmosis
Acute retinal necrosis (ARN)
Posterior outer retinal necrosis (PORN)
HIV vasculopathy
Other modalities for diagnosis
PCR
pp65 and IE-1 antigen
Lin et al. Retina 22:268–277, 2002
PCR

The study by Yamamoto et al. (2003), showed that

aqueous humor specimens which taken from 37/42
patients (88.1%) had positive CMV DNA prior treatment
and negative for inactive CMVR
Study by Smith et al. (1998) showed that 20/21 vitreous
specimens (95%) from active CMVR were positive and all
vitreous (16 samples) from healed or quiescent CMVR
were negative

Yamamoto et al. Ophthalmologica 2003;217:45–48

Smith et al. The Journal of Infectious Diseases 1999;179:1249–53
ATYPICAL RETINOCHOROIDITIS
TOXOPLASMOSIS
ACUTE RETINAL
NECROSIS
HIV VASCULOPATHY
FFA - HIV VASCULOPATHY
TAKE HOME MESSAGES

Use indirect ophthalmoscope

Treat CMV retinitis as systemic disease
Valganciclovir per-oral (very expensive)
Intravenous Ganciclovir (expensive)
collect CMVR patients for intravitreal ganciclovir
Follow the patients routinely, during treatment and after
CMVR treatment
THANK YOU
TRANSMISSIONS AND SIGNS

It is transmitted from person to person by saliva, by

breast milk, or by sexual contact; it can also be
transmitted by organ transplantation
Primary CMV infection can occur at any age :
in children, primary CMV infection - few or no
symptoms
in adults, primary CMV infection usually causes a
nonspecific febrile illness lasting 1–3 weeks associated
with a transient lymphocytosis and abnormal LFT

Carmichael A. Eye advance online publication, 16 December 2011