When hematology meets ophthalmology: Cytomegalovirus retinitis in pediatric stem cell recipients

Table 3 Summary of antiviral medications used for cytomegalovirus retinitis treatment post-hematopoietic stem cell transplant

Antiviral drug	Route of administration	Mechanism of action	Advantages	Disadvantages	Side effects
Ganciclovir[7,36-38,40,42]	Systemic: IV infusion. Local: Intravitreal injection, sustained-release implant	Inhibits viral DNA polymerase (UL54)	Selective activation by viral kinases reduces toxicity to uninfected cells. Multiple administration routes. Localized high concentration: Intravitreal injections and implants. Proven efficacy: Widely studied with established protocols for use in CMV retinitis. Adjunctive potential: Can be combined with other therapies, such as adoptive T-cell therapy, for refractory cases	Hematologic toxicity limits its systemic use in some patients. Limited oral bioavailability. Drug resistance: May develop with prolonged use. Local administration challenges: Intravitreal injections or implants are invasive and may cause complications (e.g., retinal detachment or endophthalmitis). High cost: Treatment, especially with implants or frequent intravitreal injections, can be expensive. Not curative: Requires long-term or recurrent treatment to manage chronic infection	Hematologic: Neutropenia, anemia, thrombocytopenia. Gastrointestinal: Nausea, vomiting, diarrhea, abdominal pain. Neurological: Headache, dizziness, confusion, seizures (rare). Renal: Increased serum creatinine, acute kidney injury (rare, but possible with IV administration). Ophthalmologic (intravitreal use): Retinal detachment, endophthalmitis, vitreous hemorrhage. Others: Fever, fatigue, rash or itching, injection site reactions (for IV or intravitreal routes). Rare but serious side effects: Teratogenicity, carcinogenicity, reproductive toxicity, hypersensitivity reactions
Valganciclovir[36,37]	Systemic: Oral	Prodrug of ganciclovir. After activation, inhibits viral DNA polymerase	Improved oral bioavailability compared to ganciclovir		Same side effect profile as ganciclovir
Foscarnet[7,37,38,41]	Systemic: IV infusion. Local: Intravitreal injection	Directly inhibits viral DNA polymerase (UL54)	Unlike ganciclovir, it does not require activation by viral or cellular kinases. Effective for resistant CMV: Useful in cases of ganciclovir-resistant CMV infections. Broad spectrum: Active against various herpesviruses, including CMV, HSV, and VZV. IV administration: Allows for direct delivery in severe cases or when oral therapy is not feasible	Frequent infusions: Requires multiple daily infusions, which can be burdensome. Limited use in pediatrics: Fewer pediatric-specific safety data compared to other antivirals	Nephrotoxicity: Acute kidney injury is a significant concern. Electrolyte disturbances: Hypocalcemia, hypomagnesemia, and hypokalemia. Gastrointestinal issues: Nausea, vomiting, and diarrhea. Central nervous system effects: Seizures or confusion, particularly in patients with electrolyte imbalances
Cidofovir[36]	Systemic: IV infusion	Nucleotide analog. Competitively inhibits viral DNA polymerase and incorporates into the viral DNA, leading to chain termination	Effective for resistant CMV: Active against ganciclovir-resistant CMV strains. Broad-spectrum activity: Effective against other herpesviruses, including HSV and VZV. Single weekly dosing: Less frequent administration compared to other antivirals like foscarnet	Limited pediatric data: Fewer safety and efficacy data in pediatric patients, especially post-HSCT. Requires probenecid co-administration: To reduce nephrotoxicity, probenecid is required, which adds complexity	Nephrotoxicity: Can lead to acute renal failure if not monitored carefully. Gastrointestinal symptoms: Nausea, vomiting, and diarrhea. Ocular toxicity: Potential for retinal toxicity with prolonged use. Bone marrow suppression: Can cause neutropenia or thrombocytopenia in some patients

CMV: Cytomegalovirus; HSV: Herpes simplex virus; VZV: Varicella-zoster virus; HSCT: Hematopoietic stem cell transplant.