Adenovirus

ADENOVIRAL
KERATO-CONJUNCTIVITIS
INTRODUCTION
 Highly contagious causative agent for epidemic kerato-conjunctivitis.
 80% of acute kerato-conjunctivitis cases are viral worldwide[1]
 Human Adenovirus accounts for 65-90% of these viral kerato-conjunctival
cases[1]
 72 HAdV serotypes identified with HAdV-D associated with ocular manifestation
 Categorised as Epidemic Kerato-conjunctivitis (EKC), Acute follicular
conjunctivitis (AFC) and Pharyngo-conjunctival Fever (PCF).

EPIDEMIOLOGY
 Commonest cause of viral conjunctivitis outbreaks
 Estimated 6 million new cases occur annually in United states[2]
 EKC was circulating predominantly in Asia during the early winter and spring,
whereas PCF was circulating mainly in China, Australia and the United States
during the summer[3]
 Affects all ages and demographics
 Occular morbidity seen in paediatrics and immunocompromised

Adenoviral kerato-conjunctivitis
 HAdV is non-enveloped dsDNA virus
 Genome is divided into 7 species (A-G)
Infection Genome
type association
EKC Ad-8, 19,37,54
PCF Ad-3, 4,7
 Humans only source of reservoir

 Source of infection: direct contact with
infected fomites, water and feco-oral route.
 Incubation period is 2-14 days
 Infectious upto 10-14 days after appearance of symptoms.
PATHOPHYSIOLOGY
Virus Interaction Virus

attachment of penton internalizatio
base with n into
cellular endosomes
integrin
nucleus
cytosol
uncoating
Immune response and Clinical manifestation
Innate NK cells and Adaptive T-cell mediated release of cytokines, complement
activation and antibody-mediated-cytotoxicity manifests as:
Eyelid edema
Follicular hypertrophy and
hyperemia
Contd.
Sub-epithelial corneal infiltrates Pre-auricular

lymphadenopathy
Classification of corneal infiltrates
 Stage 1: corneal vesicle are 25-30 microns and barely
perceptible on slit lamp
 Stage 2: lesions coalesce and become clearly visible on slit

lamp. These are classical deep epithelial punctate keratitis
that may resolve or progress
 Stage 3: faint subepithelial infiltrates are present beside

deep punctate keratitis
 Stage 4: nummular opacities that maybe present months to

weeks after initial episode
Lab Diagnosis
 Isolation of virus in cell cultures was considered gold standard but limitation is
timing of laboratory testing
 Enzyme immunofluorescence assay are cheaper and faster with a high sensitivity
of 91%; however, they bear a variable specificity depending on contaminations and
false positive results. Used in combination with cell culture
 radioimmune dot-blot (turnaround time 72 hours) achieved a sensitivity of 67%

(239/355) and a specificity of 93% (3065/3285) in comparison with virus culture [4]
 PCR is more timely and sensitive test for detection and quantifying of nucleic acid
having high sensitivity (100%) but low specificity (67.9%) [5] and limited by cost.
 More recent rapid antigen detecting kits (ADENO-PLUS) is able to detect 53 types of
HAdV with 88% sensitivity and 91% specificity[6]
Treatment and Management
Role of Povidone-iodine 0.4%
combination with Dexamethasone 0.1%
 Povidone–iodine, an antiseptic has broad-spectrum antimicrobial properties shown
to decrease viral spread.
 Used in conjunction with a topical corticosteroid, the steroidal component provides
symptomatic relief while the povidone–iodine destroys the virus.
 patients placed on this regimen had nearly complete recovery of signs and
symptoms of adenoviral infection in as little as 5 days [6]
 Still under phase II clinical trials

Role of cyclosporine 2% in SEI
 Local treatment with steroid eye drops nearly always succeeds in the short
term, but often leads to recurrence of SEI once they are stopped
 Treating with corticosteroids in the active phase of the infection may also be
detrimental
 In a study, cyclosporine use decreased number of medications with 66%

patient showing clinical improvement of severity of symptoms [7]
 Cyclosporine has statistically significant potential to shorten duration of

symptoms and lower incidence of SEIs at day 21[7]
 Cyclosporine can be used to wean off patient from topical steroids.

CONCLUSION
 adenoviral conjunctivitis can be a major issue as it affects healthcare workers and

patients alike.
 Epidemic keratoconjunctivitis can lead to chronic morbidity including visual
disturbance, corneal scarring, symblephara, and dry eye syndrome
 HAdV-D species (which includes HAdV types causing EKC) raises the specter of new
pathogens for the ocular surface in last 20 years
 PCR and culture have been gold standards, but PCR for adenoviral conjunctivitis is in
limited use because of cost and equipment. Rapid antigen testing appears promising
 Treatment remains mostly supportive although new drugs like fixed combination of
povidone-iodine and dexamethasone for EKC are in clinical trials.
 A randomized clinical trial comparing cyclosporine vs. placebo has not yet been
performed and could better define the natural history and effect of treatment of this
disorder.
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Adenovirus

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ADENOVIRAL

 80% of acute kerato-conjunctivitis cases are viral worldwide[1]

 Human Adenovirus accounts for 65-90% of these viral kerato-conjunctival

 72 HAdV serotypes identified with HAdV-D associated with ocular manifestation

 Categorised as Epidemic Kerato-conjunctivitis (EKC), Acute follicular

conjunctivitis (AFC) and Pharyngo-conjunctival Fever (PCF).

 Estimated 6 million new cases occur annually in United states[2]

during the summer[3]

 Affects all ages and demographics

 Occular morbidity seen in paediatrics and immunocompromised

PCF Ad-3, 4,7

 Humans only source of reservoir

Virus Interaction Virus

Innate NK cells and Adaptive T-cell mediated release of cytokines, complement

activation and antibody-mediated-cytotoxicity manifests as:

Sub-epithelial corneal infiltrates Pre-auricular

 Stage 2: lesions coalesce and become clearly visible on slit

 Stage 3: faint subepithelial infiltrates are present beside

 Stage 4: nummular opacities that maybe present months to

 radioimmune dot-blot (turnaround time 72 hours) achieved a sensitivity of 67%

 Povidone–iodine, an antiseptic has broad-spectrum antimicrobial properties shown

to decrease viral spread.

 Used in conjunction with a topical corticosteroid, the steroidal component provides

symptomatic relief while the povidone–iodine destroys the virus.

symptoms of adenoviral infection in as little as 5 days [6]

 Still under phase II clinical trials

 In a study, cyclosporine use decreased number of medications with 66%

 Cyclosporine has statistically significant potential to shorten duration of

 Cyclosporine can be used to wean off patient from topical steroids.

 adenoviral conjunctivitis can be a major issue as it affects healthcare workers and

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