What is the recommended treatment for Cytomegalovirus (CMV) retinitis?

Treatment of CMV Retinitis

For sight-threatening CMV retinitis (lesions adjacent to the optic nerve or fovea), the ganciclovir intraocular implant plus oral valganciclovir is the preferred initial therapy, while oral valganciclovir alone is adequate for small peripheral lesions. 1, 2

Initial Treatment Selection Based on Lesion Location

Sight-threatening lesions (near optic nerve or fovea):

• Ganciclovir intraocular implant PLUS oral valganciclovir 900 mg twice daily is superior to systemic therapy alone for preventing relapse 1
• Some ophthalmologists recommend an initial intravitreous ganciclovir injection at diagnosis to deliver high local drug concentration immediately until the implant can be surgically placed 1, 2
• This combination approach provides both local control and systemic protection of the contralateral eye 1

Small peripheral lesions (not immediately sight-threatening):

• Oral valganciclovir 900 mg twice daily is the preferred initial therapy due to ease of administration and avoidance of surgical/catheter complications 1
• Induction dosing: 900 mg (two 450 mg tablets) twice daily for 21 days 3
• Maintenance dosing: 900 mg once daily after induction 3

Alternative Systemic Treatment Options

All of the following are effective for CMV retinitis, though oral valganciclovir is generally preferred for ease of use 1:

• IV ganciclovir 5 mg/kg twice daily for induction, followed by maintenance dosing 1, 4
• IV foscarnet for patients with ganciclovir intolerance or resistance 1
• IV cidofovir as a third-line option, though it carries substantial nephrotoxicity risk 1, 5

Treatment Duration and Immune Recovery

• Treatment should continue until sufficient immune recovery occurs (CD4+ count >100 cells/µL sustained for 3-6 months) 1, 6
• Even small peripheral lesions should be treated rather than observed, as immune recovery uveitis may be more common with less aggressive therapy 1
• For HIV-infected patients, antiretroviral therapy (ART) should be initiated or optimized concurrently with CMV treatment 1, 5

Critical Monitoring Requirements

Ophthalmologic monitoring:

• Dilated indirect ophthalmoscopy at diagnosis, after completion of induction therapy, at 1 month, then monthly while on treatment 1
• Monthly standardized fundus photographs provide optimal documentation for detecting early relapse 1

Laboratory monitoring:

• Complete blood counts and platelet counts twice weekly during induction, then weekly during maintenance (for ganciclovir/valganciclovir) 1
• Serum electrolytes and renal function twice weekly during induction, then weekly (especially critical for foscarnet and cidofovir) 1
• Weekly CMV viral load by PCR to assess treatment response 5, 6

Dose Adjustments for Renal Impairment

Valganciclovir requires dose reduction based on creatinine clearance 3:

• CrCl ≥60 mL/min: Standard dosing (900 mg twice daily for induction, 900 mg daily for maintenance)
• CrCl 40-59 mL/min: 450 mg twice daily for induction, 450 mg daily for maintenance
• CrCl 25-39 mL/min: 450 mg once daily for induction, 450 mg every 2 days for maintenance
• CrCl 10-24 mL/min: 450 mg every 2 days for induction, 450 mg twice weekly for maintenance

Major Adverse Effects and Management

Ganciclovir/valganciclovir toxicities 1, 5, 3:

• Severe neutropenia, anemia, thrombocytopenia (most common dose-limiting toxicity)
• Nausea, diarrhea, renal dysfunction
• Treatment should not be administered if absolute neutrophil count <500/µL or platelets <25,000/µL 4

Foscarnet toxicities 1, 5:

• Nephrotoxicity and electrolyte abnormalities (hypocalcemia, hypomagnesemia, hypokalemia)
• Neurologic dysfunction including seizures
• Requires aggressive hydration and electrolyte monitoring

Cidofovir toxicities 1, 5:

• Dose-related nephrotoxicity (most significant concern)
• Ocular hypotony
• Contraindicated if renal dysfunction or proteinuria detected before infusion 1

Common Pitfalls to Avoid

• Do not delay treatment of even small peripheral lesions in patients with CD4+ counts <50 cells/µL, as complications (immune recovery retinitis, retinal detachment) are more common with larger lesions and delayed treatment 1
• Do not use oral valganciclovir alone for sight-threatening lesions adjacent to the optic nerve or fovea—these require intraocular implant plus systemic therapy 1, 2
• Do not discontinue maintenance therapy prematurely—continue until sustained immune recovery (CD4+ >100 cells/µL for 3-6 months) 1, 6
• Do not fail to adjust doses for renal impairment, as this significantly increases toxicity risk 3, 4
• Valganciclovir tablets should be taken with food to optimize absorption 3