Retinitis

Figure 14.1 Photo of the peripheral fundus showing a yellow-white granular appearing area of retinal necrosis associated with retinal hemorrhages (“pizza-pie appearance”), representing an active chorioretinal lesion due to CMV retinitis.

In patients known to have HIV or to be immunosuppressed, the diagnosis of CMV retinitis is based on the clinical examination and confirmed by positive blood cultures for CMV. In individuals not known to be HIV positive, the diagnosis is suspected based on the clinical appearance, and prompt investigation of immune status is essential.

In an effort to halt its progression and improve visual outcome, CMV retinitis requires treatment with one of five currently available virostatic agents: ganciclovir, valganciclovir, foscarnet, cidofovir, and fomivirsen (Table 14.1). The choice of the antiviral agent and its route of delivery should be based on the location and extent of the infection, potential side effects, and the effectiveness of prior treatments.

Table 14.1 Therapy for retinitis

	Agent	Regimen	Side effects
CMV retinitis	Ganciclovir	Induction of 5 mg/kg IV q12h for 14 to 21 days, then 5 mg/kg/d IV 7 d/wk or 6 mg/kg 5 d/wk 1000 mg PO three times daily as maintenance therapy	Granulocytopenia Thrombocytopenia Anemia
	Valaganciclovir	Induction dose of 900 mg twice daily PO for 14 to 21 days and maintenance dose of 900 mg once daily PO	Granulocytopenia Anemia
	Foscarnet	Induction of 60 mg/kg IV q8h for 14 to 21 days, then 90 to 120 mg/kg/d IV	Nephrotoxicity Electrolyte imbalance Seizures/headache
	Cidofovir	Induction of 3 to 5 mg/kg IV once per week for 2 weeks, then 3 mg/kg IV every 2 weeks as maintenance	Nephrotoxicity Neutropenia Uveitis
	Fomivirsen	Induction of 330-µg intravitreal injection weekly for 2 weeks, then 330-µg intravitreal injection every 4 weeks as maintenance	Uveitis Rise of intraocular pressure Visual field disturbance Retinal pigment epitheliopathy Bull’s eye maculopathy
Ocular toxoplasmosis	Pyrimethamine	75 mg PO, then 25 mg PO daily for 4 to 6 weeks	Anemia Thrombocytopenia Leukopenia
	Sulfadiazine	2 g PO, then 1 g PO four times daily for 4 to 6 weeks	Stevens–Johnson syndrome Hypersensitivity reaction Crystalluria
	Clindamycin	300 mg PO four times daily for 4 to 6 weeks	Diarrhea Pseudomembranous colitis
Acute retinal necrosis	Acyclovir	500 mg/m² IV q8h for 7 to 10 days, then 800 mg PO five times daily for 6 to 12 weeks	Localized phlebitis Elevated serum creatinine
Progressive outer retinal necrosis	Ganciclovir	Combination of intravenous and intravitreal in combination with intravenous and intravitreal foscarnet. No established dosing regimen	Granulocytopenia Thrombocytopenia Anemia
	Foscarnet	Combination of intravenous and intravitreal in combination with intravenous and intravitreal ganciclovir. No established dosing regimen	Nephrotoxicity Electrolyte imbalance Seizures/headache

Abbreviations: CMV = cytomegalovirus; IV = intravenously; PO = orally.

Ganciclovir, an inhibitor of CMV DNA polymerase, may be administered intravenously, orally, or intravitreally. Intravenous (IV) ganciclovir should be used as induction therapy for 14 to 21 days, followed by maintenance therapy by either an IV or oral route. Because ganciclovir is virostatic, maintenance therapy is required indefinitely. In patients with impaired renal function, the full dosage of ganciclovir cannot be tolerated and requires reduction. The most common side effect of ganciclovir is neutropenia, which arises in 20% to 40% of patients and is reversible on discontinuation of the drug. Ganciclovir and zidovudine may both result in granulocytopenia; the concomitant use of these two agents may result in pronounced bone marrow suppression.

The use of a sustained-release ganciclovir implant placed directly into the vitreous cavity of the eye protects against reactivation of CMV retinitis for up to 7 months. The intravitreal implant reduces intraocular recurrence of CMV retinitis and systemic side effects of ganciclovir, but it is not protective against involvement of the fellow eye or systemic CMV infection. Adverse effects associated with the ganciclovir implant include decreased vision in the postoperative period and an increased risk of retinal detachment.

Valganciclovir is a prodrug of ganciclovir and has good penetration into the vitreous cavity after oral administration. A positive response equivalent to ganciclovir given intravenously has been demonstrated with the use of oral induction therapy with valganciclovir. The adverse effects of the two drugs are similar.

Foscarnet, an inhibitor of DNA polymerase and reverse transcriptase, is administered intravenously for 14 to 21 days as induction therapy, followed by maintenance therapy indefinitely. The most common side effect of foscarnet is nephrotoxicity, which occurs in 25% of patients and is reversible with early cessation of the drug. Because foscarnet undergoes renal elimination and is nephrotoxic, careful monitoring of renal function is necessary. However, it is effective in the treatment of ganciclovir-resistant retinitis.

Cidofovir acts by inhibiting CMV DNA polymerase. It does not require virus-dependent phosphorylation for activation. The advantage of cidofovir over ganciclovir and foscarnet is that it requires less frequent IV administration: once weekly as induction for 2 weeks and once every 2 weeks for maintenance therapy thereafter. Nephrotoxicity is the most common dose-limiting side effect, which may be reduced with the concurrent administration of oral probenecid and IV hydration.

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