What is the treatment approach for a patient with suspected CMV (Cytomegalovirus) retinitis, particularly one who is immunocompromised due to HIV/AIDS or organ transplant?

Treatment of CMV Retinitis

All immunocompromised patients with CMV retinitis should receive systemic anti-CMV therapy combined with antiretroviral therapy (in HIV patients) or reduction of immunosuppression (in transplant patients), as anti-CMV treatment decreases mortality and prevents bilateral disease. 1

Initial Treatment Selection Based on Lesion Location and Severity

Sight-Threatening Lesions (Adjacent to Optic Nerve or Fovea)

• Ganciclovir intraocular implant plus oral valganciclovir 900 mg twice daily is the preferred initial therapy for immediate sight-threatening lesions, as this combination is superior to systemic therapy alone for preventing relapse 1, 2
• 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

Small Peripheral Lesions

• Oral valganciclovir 900 mg twice daily alone is adequate for small peripheral lesions due to ease of administration and avoidance of surgical complications 1, 2
• Even small peripheral lesions require treatment for 3-6 months until immune recovery occurs, as complications including immune recovery retinitis and retinal detachment are more common with larger lesions, and anti-CMV therapy decreases mortality 1

Alternative Systemic Treatment Options

Second-Line Agents

• IV ganciclovir 5 mg/kg twice daily for induction (14-21 days), followed by 5 mg/kg once daily for maintenance, is an alternative when oral therapy is not feasible 2, 3
• IV foscarnet 60 mg/kg every 8 hours for induction (14-21 days), followed by 90-120 mg/kg once daily for maintenance, is recommended for ganciclovir intolerance or resistance 2, 4

Third-Line Agent

• IV cidofovir 5 mg/kg weekly for 2 weeks, then every 2 weeks is reserved for patients who have failed or cannot tolerate both ganciclovir and foscarnet due to substantial nephrotoxicity risk 2, 5
• Cidofovir requires concurrent oral probenecid and IV saline hydration with each infusion to minimize nephrotoxicity 5

Concurrent Antiretroviral Therapy Management

• Initiate or optimize antiretroviral therapy (ART) immediately in all HIV-infected patients with CMV retinitis, as no data demonstrate adverse effects on retinitis outcomes 1
• ART alone can control CMV retinitis after immune recovery occurs, but this takes 3-6 months, during which anti-CMV therapy must continue 1
• For transplant patients, reduce immunosuppression to the minimum necessary to prevent rejection 6

Treatment Duration and Discontinuation Criteria

• Continue anti-CMV maintenance therapy until CD4+ count >100-150 cells/µL sustained for 3-6 months in HIV patients on effective ART 1, 2
• Maintenance therapy can be discontinued when immune recovery is documented by sustained CD4+ elevation and HIV viral load suppression 1
• Restart maintenance therapy if CD4+ count decreases to <50-100 cells/µL 1

Critical Monitoring Requirements

Ophthalmologic Monitoring

• Dilated indirect ophthalmoscopy at diagnosis, after completion of induction therapy, at 1 month, then monthly while on anti-CMV treatment 1, 2
• Monthly standardized fundus photographs provide optimal documentation for detecting early relapse 1, 2
• After immune recovery, decrease ophthalmologic follow-up frequency to every 3 months 1

Laboratory Monitoring

• Complete blood counts and platelet counts twice weekly during induction, then weekly during maintenance for patients receiving ganciclovir or foscarnet 1, 2
• Serum electrolytes and renal function twice weekly during induction, then weekly for all patients, especially those receiving foscarnet or cidofovir 1, 2
• For cidofovir specifically, blood urea nitrogen, creatinine, and urinalysis must be performed before each infusion; administration is contraindicated if renal dysfunction or proteinuria is detected 1

Major Adverse Effects and Management

Ganciclovir/Valganciclovir Toxicities

• Neutropenia, thrombocytopenia, anemia are the most common hematologic toxicities requiring dose adjustment or drug discontinuation 1, 2, 3
• Gastrointestinal effects include nausea and diarrhea 1, 2
• Renal dysfunction can occur but is less common than with foscarnet or cidofovir 1

Foscarnet Toxicities

• Nephrotoxicity and electrolyte abnormalities (hypocalcemia, hypomagnesemia, hypokalemia) are the most serious adverse effects 1, 2, 4
• Anemia and neurologic dysfunction can occur 2, 4
• Adequate hydration and electrolyte monitoring are essential to minimize toxicity 4

Cidofovir Toxicities

• Dose-related nephrotoxicity is the primary concern, requiring strict adherence to hydration protocols and probenecid coadministration 1, 2, 5
• Ocular hypotony can occur even in the absence of retinitis when cidofovir is used for other CMV disease 1
• Transient reactions to probenecid (constitutional symptoms, nausea) occur in approximately 56% of patients 5

Management of Treatment-Refractory Disease

Diagnostic Approach for Progressive Disease

• Pursue vitreous biopsy urgently to exclude intraocular lymphoma and obtain specimens for CMV PCR, viral culture, and resistance testing 6
• Negative blood CMV PCR does not exclude active ocular disease, as CMV retinitis can occur with undetectable viremia 6

Therapeutic Approach for Refractory Disease

• Combination IV ganciclovir plus IV foscarnet is recommended for sight-threatening, progressive CMV retinitis despite standard therapy 1, 6
• For documented ganciclovir-resistant CMV, switch to IV foscarnet 90 mg/kg twice daily for induction 6
• IV cidofovir can be considered if both ganciclovir and foscarnet have failed or are contraindicated 6

Common Pitfalls to Avoid

• Do not withhold anti-CMV therapy in ART-naïve patients with small peripheral lesions, as complications are more common with larger lesions and anti-CMV therapy decreases mortality 1
• Do not use intravitreal therapy alone without systemic coverage, as it does not protect the contralateral eye or prevent systemic CMV disease 7
• Do not delay ART initiation in patients with CMV retinitis, as no data demonstrate adverse effects on retinitis outcomes 1
• Do not discontinue maintenance therapy prematurely before documented immune recovery with sustained CD4+ count >100-150 cells/µL for 3-6 months 1, 2
• Do not use valacyclovir for CMV prophylaxis, as it is associated with increased mortality in AIDS patients 1