Commentary
Neonatal Intensive Care Eye
James Chodosh, MD, MPH - Boston, Massachusetts
The first adenovirus was isolated in 1953 by ex vivo organ
culture of a child’s adenoid specimen removed at surgery.1
In the decade that followed, 30 human adenovirus types,
distinguished from each other by laboratory-based serum
neutralization testing, were isolated from patients with
infections of respiratory, gastrointestinal, genitourinary, and
ocular mucosa. More recently, typing of human adenovi-
ruses shifted from serum neutralization to a system driven
by genomic and bioinformatics analysis of whole genome
sequences,2 and there are now 90 human adenovirus
genotypes in GenBank, with another several dozen
awaiting typing.
The manifestations and severity of ocular infection by
adenoviruses are type specific, but most types can induce a
self-limited follicular conjunctivitis. The more severe
epidemic keratoconjunctivitis (EKC) is caused most
commonly by adenovirus types 8, 37, and 64 (the latter
formerly typed as 19),3 and manifests as membranous
conjunctivitis, corneal epithelial ulceration, and delayed-
onset corneal subepithelial infiltrates. The same viruses
implicated in EKC can cause serious systemic infections. In
one such report, a baby in a neonatal intensive care (NICU)
died of adenoviral pneumonia and secondary multisystem
failure, and 3 caregivers of the neonate subsequently
developed EKC. All 4 individuals were infected with the
same adenovirus, later identified as type 56.4
In this issue, Sammons et al5 (page 137) describe a NICU
outbreak of systemic and ocular adenovirus type 3 infection.
Respiratory infections with adenovirus can be fatal,
particularly in immune-suppressed or very young patients.
Of 23 infected neonates in the report, 4 died; 3 of those had
severe underlying, life-limiting conditions. Eleven of the
neonates with respiratory infections also had conjunctivitis,
and 9 adults, including 6 employees and 3 parents, devel-
oped conjunctivitis. All of the infections, both respiratory
and ocular, neonatal and adult, were caused by the same
strain of adenovirus type 3. Although the incident case was
not identified, further investigation implicated ophthalmol-
ogists in transmission of the infection; the same adenovirus
type 3 strain identified as the causal agent in all the in-
fections was found on handheld lenses and indirect oph-
thalmoscopes used to perform examinations for retinopathy
of prematurity.
Before identification of adenoviruses as infectious
agents, and well before the first causal association between
adenovirus and EKC, ophthalmologists in the early 1940s
believed the condition was acquired in shipyards and other
work places associated with the war effort, when in reality
144 ª 2018 by the American Academy of Ophthalmology
Published by Elsevier Inc.
the infection was being transmitted via contaminated contact
tonometers in the clinics of ophthalmologists charged with
eye care for those same workers. In 1941, there were 10 000
cases of EKC in the shipyard workers of Pearl Harbor and
several thousands in workers of San Francisco shipyards,
leading to characterization of the eye infection as “shipyard
eye.”6 Without the careful epidemiologic and molecular
investigations by Sammons et al,5 the outbreak they
describe might well have been called “NICU eye.” The
authors present a cautionary tale, reminding us that
caregivers, while doing their very best to prevent and treat
disease, can also be agents of disease, in this case a
highly contagious adenovirus infection with significant
consequences for highly vulnerable neonates. Fortunately,
Sammons et al5 were able to successfully apply
epidemiologic and molecular diagnostic methodologies to
identify and then control the adenovirus NICU outbreak.
As the practice of medicine has advanced, it is easy to
forget that we remain subject to the most basic of
maladies, including infectious diseases. Vigilance with
infection-control protocols, including strict hygiene, isola-
tion, and decontamination, along with accountability of care
providers for compliance, is necessary to limit and control
communicable infections in health care settings.
References
1. Rowe WP, Huebner RJ, Gilmore LK, et al. Isolation of a
cytopathogenic agent from human adenoids undergoing spon-
taneous degeneration in tissue culture. Proc Soc Exp Biol Med.
1953;84:570e573.
2. Seto D, Chodosh J, Brister JR, et al. Using the whole-genome
sequence to characterize and name human adenoviruses.
J Virol. 2011;85:5701e5702.
3. Zhou X, Robinson CM, Rajaiya J, et al. Analysis of human
adenovirus type 19 associated with epidemic keratoconjuncti-
vitis and its reclassification as adenovirus type 64. Invest
Ophthalmol Vis Sci. 2012;53:2804e2811.
4. Robinson CM, Singh G, Henquell C, et al. Computational
analysis and identification of an emergent human adenovirus
pathogen implicated in a respiratory fatality. Virology.
2011;409:141e147.
5. Sammons JS, Graf EH, Townsend S, et al. Outbreak of
adenovirus in a neonatal intensive care unit: critical importance
of equipment cleaning during inpatient ophthalmologic exami-
nations. Ophthalmology. 2019;126:137e143.
6. Jawetz E. The story of shipyard eye. Br Med J. 1959;1:
873e876.
https://doi.org/10.1016/j.ophtha.2018.08.033
ISSN 0161-6420/18
 Commentary

Footnotes and Financial Disclosures

Financial Disclosure(s): The author(s) have made the following disclo- Correspondence:
sure(s): J.C.: Support e National Institutes of Health (grants EY013124 and James Chodosh, MD, MPH, Massachusetts Eye and Ear, Harvard Medical
EY021558); Consultant e Shire. These sources played no role in the School, 243 Charles St., Boston, MA 02114. E-mail: james_chodosh@
writing of this commentary. meei.harvard.edu.

Pictures & Perspectives

Papilledema with Dilated Scalp Veins

A 4-year-old boy with headaches and papilledema (Fig A) was found to have macrocephaly with multiple prominent subcutaneous veins
overlying the forehead and temple (Fig B). Magnetic resonance imaging showed atresia and thrombosis of the posterior sagittal sinus (white
arrow) with a persistent embryonic falcine sinus (white asterisk), and multiple enlarged tortuous cerebral veins (black arrows) (Fig C).
Multiple dilated venous collaterals were also visible around the brainstem (white arrowheads) and within the scalp (black arrows) (Fig D).
In this child with papilledema from intracranial venous hypertension, multiple prominent subcutaneous veins provided a diagnostic clue to a
congenital venous sinus atresia. (Magnified version of Fig A-D is available online at www.aaojournal.org).

MICHAEL C. BRODSKY, MD1

MEGHA M. TOLLEFSON, MD2
MAI LAN HO, MD3
1
Departments of Ophthalmology and Neurology, Mayo Clinic, Rochester, Minnesota; 2Dermatology and Pediatrics, Mayo Clinic, Rochester, Minnesota;
3
Radiology, Mayo Clinic, Rochester, Minnesota

Footnotes and Financial Disclosures

Financial Disclosure(s):: Supported in part by a grant from the Knights Templar Eye Foundation, Flower Mound, TX.

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