1. Viral retinitis, such as cytomegalovirus (CMV) retinitis, can occur in immunocompromised individuals and requires aggressive treatment. 2. CMV retinitis presents as areas of hemorrhage, whitening, and necrosis of the retina and typically occurs along the retinal arcades. 3. Treatment involves the use of antiviral drugs like ganciclovir, valganciclovir, cidofovir, and foscarnet to treat active infections and prevent recurrence in high-risk patients.

1. VIRAL RETINITIS
Dr Abhishek Ghelani

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

5. “FROSTED-BRANCH” ANGIITIS
• a perivascular form often described
as a variant of
“frosted-branch” angiitis

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

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

32. THANK YOU