Acute hemorrhagic conjunctivitis (AHC) is one of the most highly infectious diseases in the field of ophthalmology. Along with epidemic keratoconjunctivitis (EKC), it is one of the three viral conjunctivitis diseases (EKC, pharyngoconjunctival fever, and AHC) designated as surveillance targets under Japan’s Infectious Disease Surveillance (Infectious Disease Occurrence Trend Survey)1).
The causative viruses are enterovirus 70 (EV70) and coxsackievirus A24 variant (CA24v). Both are RNA viruses belonging to the Picornaviridae family, and due to their rapid genetic mutation, they have caused multiple global pandemics in the past.
This disease is also known as “Apollo disease.” In 1969, the year Apollo 11 landed on the moon, a global pandemic caused by EV70 occurred in Ghana, West Africa, and in the same year, an outbreak caused by CA24v was confirmed in Singapore. Because conjunctivitis characterized by “sun-like red bleeding” became prevalent that year, this historical nickname became established.
“Apollo disease” is a common name for acute hemorrhagic conjunctivitis. It originates from the global pandemic that started in West Africa in 1969, the year when the US Apollo 11 landed on the moon. Because conjunctivitis presenting with “sun-like red hemorrhages” spread explosively that year, it was remembered as an event of the Apollo 11 year, and this alternative name became widespread. Even today, it is diagnosed and treated ophthalmologically as acute hemorrhagic conjunctivitis.
The most characteristic features of acute hemorrhagic conjunctivitis are the short incubation period and the frequent occurrence of bulbar conjunctival hemorrhage.
Bulbar conjunctival hemorrhage (most characteristic)
Bulbar conjunctival hemorrhage (subconjunctival hemorrhage): This is the most characteristic finding, occurring in 70–90% of AHC cases 2).
The hemorrhage can vary from petechial or patchy to extensive, often spreading over 3–5 days after onset.
Some cases are accompanied by marked bulbar conjunctival edema (chemosis).
Conjunctival and lymph node changes
Palpebral conjunctival hyperemia and follicle formation: Prominent.
Preauricular lymphadenopathy: May be present but not always.
Corneal involvement: Punctate corneal epithelial erosions may occur early in the disease, but unlike in EKC, they rarely leave punctate subepithelial opacities. Visual impairment due to corneal punctate subepithelial opacities is also rare.
In cases of EV70 infection, limb paralysis (especially lower limb paralysis) following conjunctivitis has been reported 3). However, this neurological complication has not been reported with CA24v infection and is considered specific to EV70. Since EV70 infections are now rarely reported, the risk of neurological complications is practically low.
In acute hemorrhagic conjunctivitis, subconjunctival hemorrhage (bleeding on the surface of the white of the eye) occurs in 70–90% of cases, and the entire eye may appear bright red. However, this is not bleeding inside the eyeball, but blood leaking under the thin membrane (conjunctiva) covering the white of the eye. It is naturally absorbed and heals within about a week, usually leaving no sequelae, and is unrelated to vision loss or blindness.
The causative viruses of acute hemorrhagic conjunctivitis are limited to two types: EV70 and CA24v.
Enterovirus 70 (EV70)
Virus classification: Picornaviridae, Enterovirus genus
Characteristics: 7.5 kbp genome, single-stranded positive-sense RNA virus, no envelope1)
History: Prototype virus that caused a global pandemic in 1969–1970. Currently, isolation using conventional cell culture is no longer possible (last reported isolation in Saudi Arabia in 1984), and RT-PCR is required for laboratory detection.
Special notes: Neurological complications with limb paralysis have been reported, but no cases have been isolated in recent years.
Coxsackievirus A24 variant (CA24v)
Virus classification: Picornaviridae, Enterovirus genus
Characteristics: Also a single-stranded positive-sense RNA virus. No envelope1)
History: First identified in Singapore in 1970. Repeated epidemics mainly in Southeast Asia, with global spread in 1985. In Japan (Okinawa), major epidemics were recorded in 1985, 1994, and 20113)
Special notes: Currently the main cause of AHC epidemics. Can be isolated by cell culture. No neurological complications reported.
Both EV70 and CA24v are RNA viruses, which have a faster rate of genetic mutation compared to DNA viruses. This characteristic makes it easier for mutant strains that evade the immune response to emerge, and they have caused multiple global pandemics in the past 1). In the 2011 Okinawa outbreak, a new genotype of CA24v mutant strain was confirmed to be the main cause of the epidemic 3).
Clinical diagnosis of acute hemorrhagic conjunctivitis is based on the following three features.
If these three signs are present, a clinical diagnosis of AHC can be made.
| Disease | Differentiating points from AHC |
|---|---|
| Epidemic keratoconjunctivitis (EKC) | EKC: unilateral onset → delayed involvement of the other eye. Incubation period is long, about 1 week. Bulbar conjunctival hemorrhage is rare. Leaves MSI (subepithelial infiltrates). AdV rapid antigen test positive1) |
| Conjunctivitis due to adenovirus type 11 | May present with clinical features similar to AHC. Differentiated by positive AdV rapid antigen test |
| Bacterial conjunctivitis | Mainly mucopurulent discharge. Bulbar conjunctival hemorrhage is usually not seen |
| Allergic conjunctivitis | Main complaint is ocular itching. Seasonal/chronic course. No hemorrhage |
A negative result on the AdV rapid antigen detection kit (adenovirus rapid diagnostic kit) is an important clue for clinical differentiation from EKC1). While AHC typically presents with acute onset in both eyes almost simultaneously, EKC often involves one eye first, with the other eye becoming affected after a slight delay, which is also important for differentiation.
A rapid etiological diagnostic kit for EV (enterovirus) has not been developed at present. For definitive diagnosis, it is necessary to request testing at specialized institutions1).
1. RT-PCR (Reverse Transcription Polymerase Chain Reaction)
The most practical definitive diagnostic method. It can detect EV70 and CA24v simultaneously.
2. Virus Isolation
3. Antigen Detection (Fluorescent Antibody Method)
PCR detection of EV70 using conjunctival scrapings has been reported 6). However, this is a laboratory-level test and is not suitable for routine use in clinical settings.
4. Serological Tests
Serum neutralizing antibody titers against EV70 or CA24v are measured. If there is a fourfold or greater rise in antibody titer in paired sera from the acute phase and convalescent phase (10 days to 2 weeks after onset), an EV infection can be diagnosed. It is known that EV70 antibodies become undetectable 7 years after infection 5).
In RT-PCR used for definitive diagnosis of acute hemorrhagic conjunctivitis, viral RNA is often not detected unless tested very early after onset (within 3 days), when viral replication is active. AHC, as its name suggests, follows an acute course, and the virus decreases rapidly, becoming undetectable after 3 days of illness. Therefore, it is important to seek medical attention as soon as symptoms appear, rather than waiting to see how things progress.
Currently, no specific antiviral drugs against EV70 and CA24v have been established 1). Treatment mainly focuses on symptomatic therapy to relieve symptoms. In most cases, clinical symptoms improve within a few days, and spontaneous recovery occurs in about a week without sequelae.
Antibiotic eye drops (to prevent bacterial superinfection)
Antibiotic eye drops are sometimes administered not as antiviral treatment but to prevent bacterial superinfection (secondary infection). However, since clinical symptoms often improve spontaneously within a few days, they are often unnecessary 1).
Steroid eye drops
Severe cases requiring steroids are rare. Unlike EKC, AHC rarely leaves subepithelial corneal opacities, so steroid eye drops are seldom indicated 1).
Anti-inflammatory (nonsteroidal anti-inflammatory drug) eye drops
May be used adjunctively when subjective symptoms (e.g., foreign body sensation, tearing) are severe.
Because the infection is highly contagious, infection control is as important as treatment.
Personal measures
Measures at school and workplace
In domestic outbreaks, infections are common among junior and senior high school students, often leading to school closures. If infected, it is important to refrain from attending school or work according to the doctor’s advice to prevent the spread of infection.
Infection control measures in healthcare facilities
The Viral Conjunctivitis Clinical Practice Guidelines (2025 edition) recommend infection control measures similar to those for epidemic keratoconjunctivitis (EKC) 1).
Acute hemorrhagic conjunctivitis is highly contagious and spreads through contact with eye discharge or tears. The timing of returning to school or work depends on the doctor’s judgment, but it is generally advisable to refrain until the acute phase (when redness and discharge are prominent) has passed. To prevent infection within the family, avoid sharing towels and toiletries, and practice frequent handwashing. It is important for infected individuals to wash their hands after touching their eyes and to avoid touching other objects with hands that have rubbed the eyes.
The causative viruses of AHC, EV70 and CA24v, are RNA viruses belonging to the Picornaviridae family. Their main characteristics are as follows 1).
RT-PCR targeting the VP4 region using a two-parameter neighbor-joining method enables type differentiation and phylogenetic analysis covering the entire Picornaviridae family, including poliovirus4). Using this method, it was revealed that a novel genotype variant strain was the main cause of the 2011 CA24v epidemic in Okinawa3). For EV70, molecular biological methods have been the main means of identification since 1984.
In a 2015 study by Harada et al., a detailed molecular epidemiological analysis of the CA24v epidemic in Okinawa in 2011 (over 165 cases) was conducted 3). Genetic sequence analysis of the VP1 region confirmed that the epidemic strain was a novel mutant strain genetically different from conventional CA24v. This study indicates that CA24v, as an RNA virus, can cause periodic pandemics while continuously accumulating mutations.
Regarding the molecular biological detection of EV70 by RT-PCR, its effectiveness was established in a 1996 study by Uchio et al. 6). High detection sensitivity within 3 days of symptom onset was demonstrated, and it has been established as the standard molecular diagnostic method for conventionally non-culturable EV70.
Regarding the long-term dynamics of serum neutralizing antibodies, a study by Aoki & Sawada showed that neutralizing antibodies after EV70 infection decrease over time and become undetectable 7 years after infection 5). This finding provides important basic data for considering the possibility of EV70 re-emergence and the duration of post-infection immunity.
