What is the recommended treatment regimen for CMV (Cytomegalovirus) retinitis using intravitreal foscarnet in patients with AIDS (Acquired Immune Deficiency Syndrome)?

Intravitreal Foscarnet for CMV Retinitis in AIDS Patients

Intravitreal foscarnet at 2400 micrograms per injection is an effective salvage therapy for CMV retinitis in AIDS patients who cannot tolerate systemic therapy, but it requires biweekly injections and is generally not recommended as first-line treatment due to practical limitations, particularly in children. 1

Clinical Context and Indications

Intravitreal foscarnet serves as a local treatment option when systemic therapy is contraindicated or not tolerated. The primary indications include:

• Myelosuppression from systemic ganciclovir preventing continued use 2
• Renal toxicity from systemic foscarnet or cidofovir 2
• Catheter-related sepsis complicating intravenous therapy 2
• Patient refusal of systemic intravenous therapy 2

However, guidelines explicitly state that biweekly intraocular injections are impractical for use in most children and data are limited in pediatric populations. 1

Dosing Regimen

Induction Phase

• 2400 micrograms intravitreally administered twice weekly for 3 weeks (total of 6 injections) for active retinitis 2
• This regimen achieved complete resolution in 62.5% of cases and partial resolution in 37.5% 2

Maintenance Phase

• 2400 micrograms intravitreally once weekly to prevent relapse 2
• Relapse rate on maintenance was 33% by 20 weeks 2

Pharmacokinetics

Vitreous drug levels demonstrate sustained therapeutic concentrations:

• 896 μmol/L at 22.75 hours post-injection 2
• 74.9 μmol/L at 42.5 hours post-injection 2

These levels far exceed the IC50 for CMV, providing rationale for weekly maintenance dosing. 2

Critical Limitations

The major practical barrier is the requirement for biweekly injections during induction, which necessitates:

• Repeated ophthalmologic procedures under sterile conditions 1
• Patient compliance with frequent clinic visits 2
• Risk of procedure-related complications with each injection 1

Intravitreal therapy does not prevent contralateral eye involvement or systemic CMV disease, making it inferior to systemic approaches that provide protection to both eyes and other organs. 1

Safety Profile

Intravitreal foscarnet demonstrates a favorable local safety profile:

• No significant intraocular toxicity observed in clinical series 2
• No important local complications such as endophthalmitis, retinal detachment, or vitreous hemorrhage in the primary study 2
• Avoids systemic toxicities including nephrotoxicity and electrolyte disturbances that occur with IV foscarnet 1

Preferred Alternative Approaches

Current guidelines strongly favor systemic therapy over intravitreal injections as first-line treatment:

For Sight-Threatening Lesions

• Ganciclovir intraocular implant plus oral valganciclovir 900 mg twice daily is the preferred regimen 3
• Some ophthalmologists recommend a single initial intravitreous ganciclovir injection (not foscarnet) at diagnosis to provide immediate high local drug concentration until surgical implant placement 1

For Peripheral Lesions

• Oral valganciclovir 900 mg twice daily alone is adequate and preferred due to ease of administration 3

For Systemic Intolerance

• IV foscarnet 60 mg/kg every 8 hours for 14-21 days induction, then 90-120 mg/kg daily maintenance remains the standard alternative to ganciclovir 1, 4

Clinical Outcomes Comparison

When comparing intravitreal foscarnet to systemic options:

• Systemic foscarnet achieved 93.5% response rate (61.3% complete resolution) with median time to progression of 93 days 5
• Intravitreal foscarnet achieved 100% response rate (62.5% complete, 37.5% partial) but with 33% relapse by 20 weeks 2
• Combination ganciclovir plus foscarnet for refractory disease showed median time to progression of 105 days versus 39 days for foscarnet monotherapy 4

Common Pitfalls to Avoid

• Do not use intravitreal foscarnet as first-line therapy when systemic options are available, as it does not protect the contralateral eye or prevent systemic CMV disease 1
• Do not attempt in children under 3 years due to small eye size 1
• Do not rely on intravitreal therapy alone without considering systemic coverage, particularly in patients starting antiretroviral therapy 1
• Do not assume intravitreal foscarnet is equivalent to intravitreal ganciclovir—the evidence base is stronger for ganciclovir implants combined with systemic therapy 3

Practical Algorithm

When systemic therapy fails or is contraindicated:

1. First, attempt to optimize systemic therapy by switching agents (ganciclovir to foscarnet or vice versa) or using combination therapy 1
2. If systemic therapy remains impossible, consider ganciclovir intraocular implant plus oral valganciclovir rather than intravitreal injections 3
3. Reserve intravitreal foscarnet for the rare patient who cannot tolerate any systemic therapy, cannot undergo implant surgery, and has unilateral disease 2
4. Always initiate or optimize antiretroviral therapy concurrently to achieve immune reconstitution (CD4+ >100 cells/μL for 3-6 months) 3