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Research Letters |

Treatment of Congenital Cytomegalovirus Retinitis With Intravitreous Ganciclovir FREE

Maziar Lalezary, MD; Franco M. Recchia, MD; Stephen J. Kim, MD
[+] Author Affiliations

Author Affiliations: Department of Ophthalmology, Vanderbilt Eye Institute, Nashville, Tennessee.


Arch Ophthalmol. 2012;130(4):525-527. doi:10.1001/archophthalmol.2011.1615.
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Cytomegalovirus (CMV) is the most common infectious congenital syndrome worldwide, occurring in 0.2% to 2.4% of all live births.1 While most newborns with congenital CMV are asymptomatic, long-term complications can include deafness, mental retardation, and vision loss.2 Active congenital ocular disease is rare, and systemic treatment is controversial. Herein, we describe a newborn with active CMV retinitis and optic neuritis for whom systemic treatment was withheld owing to risk of toxic effects. Faced with this dilemma, we administered intravitreous ganciclovir sodium. We present our findings regarding the possible efficacy and safety of this treatment in slowing disease progression.

A premature infant with intrauterine growth restriction was born at 35 weeks' gestation weighing 1180 g. On day of life (DOL) 1, the ophthalmology department was consulted after microcephaly and intracranial calcifications were observed. Anterior segment examination findings were normal, but dilated funduscopic examination revealed extensive retinitis in both eyes with optic neuritis (Figure 1). Urine culture and polymerase chain reaction results confirmed CMV infection. Systemic ganciclovir treatment was recommended owing to optic nerve involvement.

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Figure 1. Fundus photographs of the right (A) and left (B) eyes demonstrating retinitis involving the optic nerves in both eyes and extensive frosted branch angiitis in the left eye.

Systemic ganciclovir treatment, however, was declined by the infectious disease consultants owing to risk of neutropenia. On DOL 4, intravitreous ganciclovir sodium (600 μg in 0.03-mL volume) was administered to each eye. Rapid and dramatic improvement of retinitis and optic neuritis was observed 3 days later. During the next 2 weeks, 2 additional injections were given in the right eye and 1 was given in the left eye. On DOL 25 (2 weeks following the last injection), retinitis recurred in both eyes. Systemic ganciclovir treatment was again recommended in the setting of recurrent CMV ocular infection and underlying central nervous system disease but was declined again by the infectious disease consultants. During the next 3 weeks, 3 and 4 more injections of intravitreous ganciclovir were given in the right and left eyes, respectively. By DOL 65, a total of 12 injections (6 per eye) had been administered (Figure 2). No ocular complications (cataract, retinal whitening, or inflammation) or systemic complications (neutropenia) were observed after any intravitreous ganciclovir treatment. At the most recent examination (on DOL 95), there was no sign of active disease in either eye.

Place holder to copy figure label and caption
Graphic Jump Location

Figure 2. Fundus photographs of the right (A) and left (B) eyes demonstrating rapid and dramatic resolution of retinitis after serial intravitreous ganciclovir sodium injections.

To our knowledge, this is the first report of intravitreous ganciclovir treatment for active congenital CMV retinitis. We derived the dose (600 μg) from the standard adult dose (2 mg/0.1 mL) by adjusting for the smaller eye volume in the infant. The lack of observed complications and rapid response to each of 12 treatments support the safety of this dose.

In a 10-year prospective study by Coats et al2 that screened for congenital infections, only 1 immunocompetent newborn had active retinitis. Because the disease is considered to be self-limiting and systemic treatment can be harmful, treatment remains controversial. In 2003, the National Institute of Allergy and Infectious Diseases Collaborative Antiviral Study Group conducted a pharmacokinetic-pharmacodynamic study3 establishing a safe dose of intravenous ganciclovir in infants with CMV. A subsequent phase 3 randomized controlled study3 demonstrated the benefit of systemic ganciclovir therapy in reduction of hearing loss in congenital CMV infection with central nervous system involvement. While two-thirds of infants receiving treatment developed neutropenia, no deaths were related to the use of intravenous ganciclovir.4 Rapid resolution of CMV retinitis in immunocompetent infants has been reported with systemic ganciclovir treatment in 2 isolated cases.2,5 In our particular case, optic nerve involvement made complete remission unlikely with intravitreous ganciclovir treatment alone. Nevertheless, treatment temporarily arrested the disease and potentially reduced the degree of tissue damage.

The optimal treatment for congenital CMV retinitis remains unknown. Our case and those of others demonstrate that congenital CMV retinitis can persist for months after diagnosis before resolving spontaneously.6 Early treatment of active cases therefore is recommended to preserve vision.5 If systemic treatment is delayed or withheld owing to potential toxic effects, intraocular treatment can be used as an adjunctive or alternative treatment to limit retinal and optic nerve damage. The results of our case may therefore assist the management of future cases.

Correspondence: Dr Kim, Department of Ophthalmology, Vanderbilt Eye Institute, 2311 Pierce Ave, Nashville, TN 37232 (skim30@gmail.com).

Financial Disclosure: Dr Kim is a paid consultant for Ophthotech Corp.

Funding/Support: This work was supported in part by an unrestricted grant from Research to Prevent Blindness to the Department of Ophthalmology and Visual Sciences, Vanderbilt University School of Medicine.

Weller TH. The cytomegaloviruses: ubiquitous agents with protean clinical manifestations, II.  N Engl J Med. 1971;285(5):267-274
PubMed   |  Link to Article
Coats DK, Demmler GJ, Paysse EA, Du LT, Libby C. Ophthalmologic findings in children with congenital cytomegalovirus infection.  J AAPOS. 2000;4(2):110-116
PubMed   |  Link to Article
Kimberlin DW, Lin CY, Sánchez PJ,  et al; National Institute of Allergy and Infectious Diseases Collaborative Antiviral Study Group.  Effect of ganciclovir therapy on hearing in symptomatic congenital cytomegalovirus disease involving the central nervous system: a randomized, controlled trial.  J Pediatr. 2003;143(1):16-25
PubMed   |  Link to Article
Nassetta L, Kimberlin D, Whitley R. Treatment of congenital cytomegalovirus infection: implications for future therapeutic strategies.  J Antimicrob Chemother. 2009;63(5):862-867
PubMed   |  Link to Article
Barampouti F, Rajan M, Aclimandos W. Should active CMV retinitis in non-immunocompromised newborn babies be treated?  Br J Ophthalmol. 2002;86(2):248-249
PubMed   |  Link to Article
Coors LE, Spencer R. Delayed presentation of cytomegalovirus retinitis in an infant with severe congenital cytomegalovirus infection.  Retina. 2010;30(4):(suppl)  S59-S62
PubMed   |  Link to Article

Figures

Place holder to copy figure label and caption
Graphic Jump Location

Figure 1. Fundus photographs of the right (A) and left (B) eyes demonstrating retinitis involving the optic nerves in both eyes and extensive frosted branch angiitis in the left eye.

Place holder to copy figure label and caption
Graphic Jump Location

Figure 2. Fundus photographs of the right (A) and left (B) eyes demonstrating rapid and dramatic resolution of retinitis after serial intravitreous ganciclovir sodium injections.

Tables

References

Weller TH. The cytomegaloviruses: ubiquitous agents with protean clinical manifestations, II.  N Engl J Med. 1971;285(5):267-274
PubMed   |  Link to Article
Coats DK, Demmler GJ, Paysse EA, Du LT, Libby C. Ophthalmologic findings in children with congenital cytomegalovirus infection.  J AAPOS. 2000;4(2):110-116
PubMed   |  Link to Article
Kimberlin DW, Lin CY, Sánchez PJ,  et al; National Institute of Allergy and Infectious Diseases Collaborative Antiviral Study Group.  Effect of ganciclovir therapy on hearing in symptomatic congenital cytomegalovirus disease involving the central nervous system: a randomized, controlled trial.  J Pediatr. 2003;143(1):16-25
PubMed   |  Link to Article
Nassetta L, Kimberlin D, Whitley R. Treatment of congenital cytomegalovirus infection: implications for future therapeutic strategies.  J Antimicrob Chemother. 2009;63(5):862-867
PubMed   |  Link to Article
Barampouti F, Rajan M, Aclimandos W. Should active CMV retinitis in non-immunocompromised newborn babies be treated?  Br J Ophthalmol. 2002;86(2):248-249
PubMed   |  Link to Article
Coors LE, Spencer R. Delayed presentation of cytomegalovirus retinitis in an infant with severe congenital cytomegalovirus infection.  Retina. 2010;30(4):(suppl)  S59-S62
PubMed   |  Link to Article

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