2. CMV RETINITIS
• Herpesviridae
• neurotropic virus
• in HIV - Rate - 15–40% (declining after HAART), typically with CD4+ ≤50 cells/μL,
• HAART era - may develop CMV retinitis with CD4 > 100/μL,
• leukemia, lymphoma, transplant recipients, conditions requiring systemic
immunomodulation
• demands aggressive treatment
• ? presenting sign of systemic CMV infection
3. A CLASSIC OR FULMINANT
• retinitis - large areas hemorrhage against
whitened, edematous,
or necrotic retina
• appears in the posterior pole
• Typically along arcades
• More risk to CMV encephelitis
4. PERIPHERAL (CMV) RETINITIS
• minimal retinal hemorrhage, less aggressive
• After healing - glial scar and only minimal pigmentary changes
6. • vitritis and anterior uveitis
• optic atrophy - widespread retinal destruction
• CMV encephalitis especially when the retinitis involves the peripapillary region
7. INVESTIGATION
• Congenital CMV
• PCR testing in urine, saliva, and subretinal fluid
• complement-fixation test is of value 5–24 months
• Congenital CMV retinitis is usually associated with other systemic manifestations
• fever, thrombocytopenia, anemia, pneumonitis, and hepatosplenomegaly
• in patients with HIV/AIDS or undergoing IMT is essentially clinical
8. TREATMENT
• FDA approved drugs for CMV retinitis
• ganciclovir,
• valganciclovir,
• cidofovir,
• foscarnet
9. TREATMENT
• Principle - antiretroviral regimens - increased risk in mortality
• IV ganciclovir (5 mg/kg twice daily) * 2 weeks or
• or oral valganciclovir (900 mg twice daily) * 3 weeks or
• IV foscarnet (90 mg/kg twice daily) * 2 weeks
• IV cidofovir 5 mg/kg weekly for approximately 3 weeks
• maintenance therapy oral valganciclovir (900 mg/day)
• Can be Discont. On sustained immune recovery (CD4+ T ≥100 cells/μL for 3–6 months)
provided HAART cont.
• risk for recurrence - monitored at 3-month intervals
10. SIDE-EFFECTS OF GANCICLOVIR
• granulocytopenia, defined as <500 neutrophils per microliter
• neurologic dysfunction, abnormal liver function tests,
• and rarely, thrombocytopenia
• Resistance
• alternating foscarnet–ganciclovir - reported to be effective
11. VALGANCICLOVIR
• oral
• Diarrhea - the most common adverse effect
• nausea, fever,
• neutropenia (neutrophil count <500 cells/μL),
• anemia (hemoglobin <8.0 g/dL), and
• thrombocytopenia (platelet count <25, 000 cells/μL)
12. FOSCARNET
• inhibits the DNA polymerase of herpesviruses
• Nephrotoxic – dose limitng
• Hypocalcemia – arrhythmia, seizures
• Bone-marrow suppression - neutropenia, anemia, and thrombocytopenia
• In patients resistant to ganciclovir
• not as well tolerated as ganciclovir
13. CIDOFOVIR
• Nephrotoxicity
• Dose reduction
• administration of probenecid 2 g orally 2 hours before, and 1 g 2 hours and 8 hours after
injection .
• 1 liter of normal saline 1 hour before infusion
• Nutropenia
• Iritis, hypotony
14. CMV RESISTANCE
• In patients on maintenance therapy
• cross-resistance – better to use combination
• intravitreal therapies appear to be more effective in such circumstances
15. COMBINATION THERAPIES: GANCICLOVIR–
FOSCARNET
• multiple intravenous infusions daily
• continuation of previous maintenance therapy plus induction with the other drug for
2 weeks followed by
• Maintenance therapy with both drugs,
• ganciclovir sodium at 5 mg/kg per day and
• foscarnet sodium at 90 mg/kg per day
16. INTRAOCULAR THERAPY
• who cannot tolerate intravenous systemic therapy because of myelotoxicity
• Disadv. - extraocular systemic CMV and the fellow eye untreated
• Ganciclovir 2 mg twice a week
• Foscarnet 2.4 mg given one or two times weekly
• Cidofovir 20 μg every 6 weeks
• iritis and hypotony (simillar to systemc route)
17. IMMUNE RECOVERY UVEITIS
• immune reconstitution
• CMV antigens persist at the borders of clinically healed CMV lesions after
treatment with ganciclovir
• Healed CMV lesions with
• iritis, vitritis, macular edema, and ERM formation VMT, PVR, panuveitis with
hypopyon, and uveitic angle closure glaucoma, posterior synechia
• Rx - Periocular steroids - ?recurrence
18. • Acute retinal necrosis (ARN) is part of a spectrum of necrotizing herpetic
retinopathies
• Immunocompromised, CD4 count is usually above 60/μL
• fifth and seventh decades of life
NECROTISING AND NON NECROTIZING
HERPATIC RETINITIS
19. • most common - VZV infection, followed by HSV-1, HSV-2, rarely, CMV
• acute unilateral loss of vision, photophobia, floaters, and pain
• Fellow eye involvement - approximately 36% of cases, usually within 6 weeks, but
may be delayed
• significant AC inflammation, KPs, posterior synechiae, IOP, heavy vitreous
infiltration
• Within 2 weeks, the classic triad evolves
• occlusive retinal arteriolitis
• vitritis,
• multifocal yellow-white peripheral retinitis
20. • Early on, the peripheral retinal lesions are
discontinuous and arise in the outer retina
• vitritis, arteriolitis
21. • Within days the lesions coalesce to form a
confluent 360° creamy retinitis that progresses
in a posterior direction, leaving full-thickness
retinal necrosis, arteriolitis, phlebitis, and
occasional retinal hemorrhage
22. • Widespread necrosis of the midperipheral
retina, multiple posterior retinal breaks, and PVR
predispose eyes to combined detachments in
75% of patients
• posterior pole tends to be spared
23. • The optic nerve is frequently involved - disc swelling and RAPD
• diagnosis is made clinically, important differential diagnosis -
• CMV retinitis,
• atypical toxoplasmic retinochoroiditis
• syphilis,
• lymphoma, leukemia,
• autoimmune vasculitis - Behçet disease
• (PCR) testing of aqueous and/or vitreous samples
• Quantitative PCR - additional information - viral load, disease activity, and response
to therapy
24. • Goldmann-Witmer (GW) coefficient - measure of host response to a specific microbial
pathogen
• A ratio of greater than 3 is considered diagnostic of local antibody production
25. TREATMENT
• IV acyclovir, 10 mg/kg every 8 hours for 10–14 days
• frank renal insufficiency, the dosage - reduced
• Oral valacyclovir at doses of up to 2 g 3 times daily (oral alternative)
• IV Foscarnet for acivir resistant (90 mg/kg twice daily)
• After 24–48 hours of antiviral therapy,
• systemic corticosteroids (prednisone, 1 mg/kg/day) - to treat active inflammation and are
tapered over weeks
• Contraindicated in HIV and advanced immunisuppresion
26. • Maintenance –
• should be continued for 3 months, indefinitely in HIV patients
• Acivir 800 mg 5 times a day
• valacyclovir at 1 g orally 3 times daily
• or famciclovir at 500 mg orally 3 times daily
• ARN due to HSV – maintenance at half doses
27. • intravitreal ganciclovir (2.0 mg/0.1 mL)
• foscarnet (2.4 mg/0.1 mL)
• For rapid induction or for disease that fails to respond to systemic acyclovir
• short intravitreal half-life of these drugs - injections need to be repeated twice
weekly until the retinitis is controlled
• prophylactic barrage - at the posterior border of the necrotic lesions, prevent RD
28. PORN
• PORN - a morphologic variant of ARN
• The most common cause of PORN is VZV infection
• occurring in profoundly immunosuppressed - most often in advanced AIDS (CD4+ T
lymphocytes ≤50 cells/μL)
• retinitis begins as patchy outer retinal whitening that coalesce rapidly
• in contrast to ARN, the posterior pole may be involved early in the
• vitritis typically absent
• retinal vasculature is minimally involved, at least initially
• Perivascular clearing of the retinal opacification is characteristic of PORN syndrome
29.
30. TREATMENT
• PORN is often resistant to treatment with intravenous acyclovir alone
• successful management reported with combination systemic and intraocular therapy
using foscarnet and ganciclovir
31. NONNECROTIZING HERPETIC RETINITIS
(NONNECROTIZING
POSTERIOR UVEITIS)
• Children - acute retinochoroiditis with diffuse hemorrhages
• Adults - chronic choroiditis or vasculitis
• PCR-based assays – herpes viral etiology in 13% of cases deemed “idiopathic
posterior uveitis
• initially resistant to conventional therapy with systemic corticosteroids or (IMT),
but favorable response is achieved when patients are switched to systemic antiviral
medication
