Journal of Pediatric Ophthalmology and Strabismus

Short Subjects 

Dual Intravitreal Injections With Foscarnet and Ganciclovir for Ganciclovir-Resistant Recurrent Cytomegalovirus Retinitis in a Congenitally Infected Infant

Joseph D. Boss, MD; Kevin Rosenberg, MD; Rajiv Shah, MD

Abstract

Resistant strains of cytomegalovirus can be difficult to treat in cases of congenital cytomegalovirus retinitis. The authors describe a case of recurrent bilateral congenital cytomegalovirus retinitis in an immunocompetent newborn with ganciclovir resistance successfully treated uniquely with dual therapy of intravenous ganciclovir and foscarnet and dual intravitreal injections with ganciclovir and foscarnet. [J Pediatr Ophthalmol Strabismus. 2016;53:e58–e60.]

Abstract

Resistant strains of cytomegalovirus can be difficult to treat in cases of congenital cytomegalovirus retinitis. The authors describe a case of recurrent bilateral congenital cytomegalovirus retinitis in an immunocompetent newborn with ganciclovir resistance successfully treated uniquely with dual therapy of intravenous ganciclovir and foscarnet and dual intravitreal injections with ganciclovir and foscarnet. [J Pediatr Ophthalmol Strabismus. 2016;53:e58–e60.]

Introduction

As the leading cause of congenital viral infections worldwide, cytomegalovirus has an incidence varying from 0.5% to 2% of all live births.1,2 Congenital cytomegalovirus retinitis presents differently in immunocompetent infants compared to immunosuppressed infants, and varies in presentation from adult cytomegalovirus retinitis. Characteristic non-ophthalmic signs of congenital cytomegalovirus infection include prematurity, intrauterine growth retardation, hepatosplenomegaly, jaundice, thrombocytopenia, microcephaly, and intracranial calcifications. Long-term non-ophthalmic problems from congenital cytomegalovirus infection include sensorineural hearing loss and neurodevelopmental delay with mental retardation and motor impairment.1,3 Although the large majority of congenital cytomegalovirus infections are asymptomatic, ophthalmic symptoms can include visual impairment varying from cortical, optic nerve, and/or retinal abnormalities, in addition to possible strabismus.4,5 We describe a case of recurrent bilateral congenital cytomegalovirus retinitis in an immunocompetent newborn with ganciclovir resistance successfully treated uniquely with dual therapy of intravenous ganciclovir and foscarnet and dual intravitreal injections with ganciclovir and foscarnet.

Case Report

A 7-week-old immunocompetent premature infant born at 36 weeks with intrauterine growth restriction, congenital pericardial effusion, and patent ductus arteriosus was transferred to our medical facility. Outside HIV testing was negative; however; TORCH testing was positive for cytomegalovirus, and an outside ophthalmologist subsequently diagnosed cytomegalovirus retinitis. The infant was transferred to our care due to progression of cytomegalovirus retinitis despite 6 weeks of intravenous ganciclovir. Ophthalmic examination under anesthesia showed diffuse findings of frosted branch angiitis and cytomegalovirus retinitis in the right eye and frosted branch angiitis in zone 1 with multiple foci peripherally of cytomegalovirus retinitis in the left eye (Figures 12). The patient received intravitreal injection of both ganciclovir (2 mg) and foscarnet (1.2 mg) into both eyes on the day of presentation, and a vitreous tap was performed for further analysis. Both intravenous ganciclovir (6 mg/kg dose twice a day) and foscarnet (100 mg/kg/day) were initiated on the day of presentation.


Fundus photographs of the (A) right and (B) left eyes demonstrating cytomegalovirus retinitis and extensive frosted branch angiitis of both eyes.

Figure 1.

Fundus photographs of the (A) right and (B) left eyes demonstrating cytomegalovirus retinitis and extensive frosted branch angiitis of both eyes.


Fundus photographs of the right eye showing (A) hemorrhagic retinitis and (B) retinal necrosis. (C) Fluorescein angiography of the right eye highlighting vasculitis of the inferior arcade.

Figure 2.

Fundus photographs of the right eye showing (A) hemorrhagic retinitis and (B) retinal necrosis. (C) Fluorescein angiography of the right eye highlighting vasculitis of the inferior arcade.

The cytomegalovirus viral load from the vitreous tap was 2,330 copies/mL in the right eye and 58,300 copies/mL in the left eye. The serum cytomegalovirus viral load was 50,500 copies/mL. Cytomegalovirus resistance testing UL97 and UL54 was performed, returning negative for resistance to foscarnet or ganciclovir. The patient received a second set of intravitreal injections 2 weeks later with both ganciclovir and foscarnet in both eyes. At this time, the serum cytomegalovirus viral load was 67,250 copies/mL. Days after this second set of injections, there was improvement in the cytomegalovirus retinitis bilaterally, and intravenous foscarnet was subsequently discontinued.

However, the cytomegalovirus retinitis activity recurred days later, and the cytomegalovirus viral load increased to 194,250 copies/mL. Intravenous foscarnet was then restarted, resulting in a decline in the viral load to 28,250 copies/mL within 2 days. Given concern for cytomegalovirus resistance, the UL97 resistance was retested and returned positive for resistance to ganciclovir and susceptible to foscarnet. Intravenous foscarnet and ganciclovir were both continued.

The patient received a third injection of intravitreal foscarnet into the left eye 2 weeks after the second injection date, with laser photocoagulation done at this time to the right eye surrounding the atrophic retina. The cytomegalovirus retinitis resolved in the right eye, with near resolution in the left eye. A total of 62 days of intravenous ganciclovir and foscarnet was completed. Two months later, the patient received a fourth intravitreal injection of foscarnet in the left eye and underwent laser photocoagulation in the left eye. Soon after, the cytomegalovirus retinitis activity in the left eye resolved, the intravenous antivirals were discontinued, and the patient was placed on a 6-month course of oral valgancyclovir (16 mg/kg twice a day) in an effort to minimize hearing loss. The patient was last seen at age 13 months with complete resolution of viral activity in both eyes.

Discussion

Of congenitally infected infants with cytomegalovirus, 10% will become symptomatic and require treatment.3 There are four licensed antiviral drugs for the treatment of cytomegalovirus infection: ganciclovir, oral valgancyclovir, cidofovir, and foscarnet. Current treatment guidelines recommend intravenous ganciclovir for 3 to 6 weeks if central nervous system or focal organ disease occur.6

Cytomegalovirus resistance to ganciclovir or foscarnet is rare, but has been reported. The rate of ganciclovir resistance in baseline infections is less than 3%; however, resistance increases with longer duration of intravenous ganciclovir, with as high as 11.4% at 6 months and 27.5% at 9 months of therapy.7 In cases of contraindications or resistance to intravenous ganciclovir, off-label intravitreal injections of either ganciclovir or less commonly with foscarnet have been described in case reports.8–11 Differing in mechanism of action from ganciclovir, foscarnet can be helpful as an alternative or adjunctive therapeutic agent in cytomegalovirus strains resistant to ganciclovir, or when ganciclovir is medically contraindicated.

To our knowledge, this is the first report of dual use of intravitreal ganciclovir and foscarnet for active ganciclovir-resistant cytomegalovirus retinitis in a congenitally infected premature infant. Additionally, this case highlights the important consideration of retesting resistance in cases of progressive disease despite treatment.

Congenital cytomegalovirus infections remain a significant cause of morbidity and mortality among newborns. This rare case of ganciclovir-resistant cytomegalovirus retinitis highlights the importance of having multiple therapeutic options. We report a case of successful treatment with dual intravenous ganciclovir and foscarnet in addition to bilateral dual intravitreal injection therapy with ganciclovir and foscarnet in this potentially blinding condition.

References

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  10. Oschman A, Murthy V, Kollipara R, Kenneth Lord R, Oluola O. Intravitreal ganciclovir for neonatal cytomegalovirus-associated retinitis: a case report. J Perinatol. 2013;33:329–331. doi:10.1038/jp.2012.139 [CrossRef]
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Authors

From Kresge Eye Institute, Wayne State University, Detroit, Michigan.

The authors have no financial or proprietary interest in the materials presented herein.

Correspondence: Joseph D. Boss, MD, Kresge Eye Institute, 4717 St. Antoine St., Detroit MI 48201. E-mail: jboss@med.wayne.edu

Received: May 23, 2016
Accepted: July 18, 2016
Posted Online: October 22, 2016

10.3928/01913913-20161003-02

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