Clinical
Viral Diseases of the Eye
Last reviewed 7 July 2026
Viruses cause disease in every part of the eye, from the eyelid to the retina, and the field can be read two ways: by the clinical syndrome, classified by the structure inflamed, or by the pathogen. The two views complement each other, because most syndromes have several viral causes and most viruses can involve more than one structure. A few facts orient the whole subject: herpes simplex keratitis is a leading infectious cause of corneal blindness, cytomegalovirus retinitis is an AIDS-defining illness, adenovirus is the commonest cause of viral conjunctivitis, and measles is the commonest cause of childhood blindness in low-income countries.
The eye is also unusual in being immune-privileged, which shapes its viral disease. The detailed virology of the individual agents lives in their own profiles; here they are treated as clinical syndromes and organ-tropic infections.
Anatomy and immune privilege
The eye has three layers: an outer coat of cornea and sclera, a middle vascular uvea (iris, ciliary body and choroid), and the inner neural retina. The transparent, avascular cornea is protected by the tear film, which carries antimicrobial proteins and immunoglobulins (IgA and IgG) that impede viral attachment.
Because uncontrolled inflammation would destroy the delicate optical tissues, the eye suppresses local immune responses, a set of adaptations called anterior chamber-associated immune deviation, or immune privilege, reinforced by blood-ocular barriers. This privilege is double-edged: it limits defence against viruses, and much ocular viral damage is caused by the host immune response rather than the virus itself, which is why immunosuppressive corticosteroids are both useful and dangerous in ocular viral disease.
The ocular syndromes
The syndromes are defined by the structure involved, and each has a viral differential.
| Syndrome | Principal viral causes | Features |
|---|---|---|
| Conjunctivitis | Adenovirus, HSV, VZV, EBV, measles, mumps, enterovirus, molluscum | Follicular, papillary, membranous or haemorrhagic |
| Keratitis | HSV, VZV, adenovirus, measles, mumps, rubella, vaccinia | Epithelial (dendritic) or stromal |
| Scleritis / episcleritis | HSV, VZV, mumps, EBV, influenza | Episcleritis milder, better prognosis |
| Uveitis | HSV, VZV, EBV, mumps, adenovirus, vaccinia | Usually anterior |
| Retinitis | CMV, HIV, HSV, VZV | Necrotising; sight-threatening |
| Adnexal disease | HSV, VZV, molluscum, papillomavirus, HHV-8 | Blepharitis, lid lesions, Kaposi sarcoma |
Conjunctivitis is the commonest ocular syndrome and is most often viral, with adenovirus the leading cause; the inflammatory response may be follicular (lymphoid aggregates), papillary (oedema), or, when severe, membranous.
Keratitis, inflammation of the cornea, is the sight-threatening syndrome: HSV in particular causes a keratitis that can blind, with epithelial disease producing dendritic or geographical ulcers and stromal disease producing disciform or interstitial keratitis. Scleritis is a severe, often systemically-treated inflammation, while the more superficial episcleritis is milder with a better prognosis.
Uveitis is inflammation of the uveal tract; the viral causes are mostly anterior, though most uveitis overall is non-infectious. Retinitis is potentially blinding and has become far more prominent with HIV; the necrotising herpetic retinopathies, acute retinal necrosis (ARN) in the immunocompetent and progressive outer retinal necrosis (PORN) in the immunosuppressed, are caused chiefly by VZV and HSV. Adnexal disease affects the eyelids and lacrimal apparatus.
HIV and the eye
HIV is a major ocular pathogen, both directly and by opening the eye to opportunists. About 70% of people with AIDS develop eye disease. The manifestations fall into four groups: microvasculopathy (HIV retinopathy, with asymptomatic cotton-wool spots and micro-aneurysms, the commonest posterior finding), opportunistic infections (CMV, HSV and VZV, and non-viral agents such as toxoplasma and syphilis), neoplasms (Kaposi sarcoma, lymphoma), and neuro-ophthalmic disease. Eye infections in HIV tend to be more severe, bilateral and multicentric.
Herpesviruses
The herpesviruses combine latency with cytopathic effect, giving persistent infection with reactivation, and they account for much of the serious ocular viral disease.
Herpes simplex virus
HSV reaches the eye and remains latent in the trigeminal ganglion, reactivating to cause recurrent disease. Infectious epithelial keratitis produces the classic dendritic ulcer, a branching lesion best seen after fluorescein staining that usually heals in five to twelve days; misuse of topical steroids lets it enlarge into a geographical ulcer. Stromal keratitis is the commonest sight-threatening form, an immune-mediated reaction that leaves permanent scarring and may need a corneal graft, and loss of corneal sensation is a useful sign. Other manifestations include iridocyclitis, uveitis and, rarely, acute retinal necrosis.
Diagnosis is usually clinical, but where needed PCR of aqueous or vitreous fluid is more sensitive than culture, and intraocular antibody production can be shown with the Goldmann-Witmer coefficient. Treatment uses antivirals as the mainstay: topical aciclovir or trifluridine for epithelial disease, and systemic aciclovir, valaciclovir or famciclovir for deeper or immunocompromised disease, with long-term oral aciclovir reducing recurrences. Topical corticosteroids are never used alone for epithelial keratitis, because they let the virus replicate freely, but under antiviral cover they help control stromal inflammation.
Cytomegalovirus
CMV retinitis is an AIDS-defining illness that occurs at a CD4 count below about 50 cells per cubic millimetre, and its incidence has fallen sharply with antiretroviral therapy. It is a painless, slowly progressive, full-thickness retinal necrosis with haemorrhage and little inflammatory reaction, and the histological hallmark is the owl’s eye intranuclear inclusion. Untreated, it destroys the retina within about six months and, in half of cases, becomes bilateral. Diagnosis is largely clinical, supported by PCR of ocular fluid and blood. Treatment combines antiretroviral therapy with ganciclovir or its oral prodrug valganciclovir, foscarnet or cidofovir, given systemically and, where needed, by intravitreal injection or implant.
Varicella-zoster virus
VZV becomes latent after chickenpox and reactivates as herpes zoster. Herpes zoster ophthalmicus (HZO) is zoster in the ophthalmic division of the trigeminal nerve and complicates about 10% to 20% of zoster. A vesicle on the tip of the nose, Hutchinson’s sign, reflects nasociliary involvement and predicts ocular disease in about half of cases. HZO can involve the lid, conjunctiva, sclera, cornea and iris, and cause PORN; postherpetic neuralgia is a serious complication, not prevented by early antivirals or steroids. Treatment is with aciclovir, valaciclovir or famciclovir, intravenous aciclovir being the choice in the immunosuppressed to prevent dissemination, and oral therapy started within 72 hours speeds resolution and reduces ocular complications.
Epstein-Barr virus and other herpesviruses
EBV most often causes periorbital oedema and follicular conjunctivitis with acute mononucleosis, but has been implicated in keratitis, uveitis and retinitis; treatment is supportive. Among the remaining herpesviruses, HHV-6 rarely causes optic neuritis and conjunctivitis, and HHV-8 causes conjunctival Kaposi sarcoma.
Adenoviruses
Adenoviruses are the commonest cause of viral conjunctivitis. Being non-enveloped, they are highly resistant to disinfection and survive on instruments and surfaces, causing epidemics including in eye clinics. After an incubation of 2 to 14 days they cause acute, usually self-limiting disease, and viral shedding continues for up to two weeks. The manifestations form four syndromes.
| Syndrome | Common serotypes | Features |
|---|---|---|
| Epidemic keratoconjunctivitis (EKC) | 8, 19, 37 | Highly contagious; subepithelial infiltrates may reduce vision |
| Pharyngoconjunctival fever (PCF) | 3, 4, 7, 11, 14 | Fever, sore throat, bilateral conjunctivitis; mainly children |
| Nonspecific follicular conjunctivitis | 3, 4, 7 | Mild, self-limiting, commonest form |
| Chronic keratoconjunctivitis | Various | Rare; prolonged irritation |
Diagnosis is clinical, supported by PCR (more sensitive than culture). There is no approved specific antiviral, so management is prevention of transmission and symptomatic care; povidone-iodine drops are a cheap, broad-spectrum option, and membranes and severe keratitis are managed with topical steroids under close supervision.
Picornaviruses
Enteroviruses and parechoviruses cause conjunctivitis, keratoconjunctivitis and uveitis, reaching the eye by hand-to-eye contact or after gut replication. The distinctive syndrome is acute haemorrhagic conjunctivitis, caused by a variant of coxsackievirus A24 and by enterovirus 70, an explosive, usually bilateral conjunctivitis with subconjunctival haemorrhages that is self-limiting. Diagnosis is by PCR or culture of conjunctival scrapings, and topical steroids are avoided because of the risk of corneal perforation.
Measles
After an incubation of about 8 to 12 days, measles begins with fever, cough, coryza and conjunctivitis, and its ocular signs appear in the prodrome as a conjunctivitis with Koplik spots that can progress to epithelial keratoconjunctivitis. In malnourished children, especially with vitamin A deficiency, measles causes corneal ulceration, keratomalacia and perforation, and is the commonest cause of childhood blindness in developing countries. Measles depresses serum retinol, so vitamin A supplementation is a treatment priority, alongside lubrication and management of secondary bacterial infection.
Poxviruses
Molluscum contagiosum causes umbilicated eyelid nodules and a chronic follicular conjunctivitis that is a reaction to viral particles shed into the tear film; lesions are florid and extensive in HIV, where they are recognised as an ocular complication of AIDS. Most resolve spontaneously; cryotherapy, curettage or cidofovir are used when treatment is needed. Vaccinia can cause ocular disease after smallpox vaccination, with eyelid pustules, conjunctivitis and, in about 30%, keratitis; vaccinia immune globulin is the approved treatment for severe complications.
Human papillomavirus
HPV causes eyelid warts and conjunctival papillomas (types 6 and 11), and conjunctival squamous cell carcinoma associated with types 16 and 18. Treatment of conjunctival lesions is by excision, with cryotherapy or cautery to the base; incomplete excision recurs, and severe disease may be treated with interferon or topical cytotoxics.
Ocular disease in systemic viral illness
Many systemic infections involve the eye, often as conjunctival injection with retro-orbital pain. Avian influenza (notably the H7 subtypes) causes conjunctivitis; mumps most often causes dacryoadenitis, with conjunctivitis and occasionally a self-limiting interstitial keratitis; HTLV-1 causes a uveitis with vitreous opacities and retinal vasculitis, alone or with its myelopathy; BK virus can cause an atypical retinitis on reactivation; and chronic hepatitis C is associated with dry eye syndrome. Among the haemorrhagic fever viruses, the filoviruses Ebola and Marburg cause conjunctivitis, and Ebola can cause a severe uveitis in convalescence with viable virus in the aqueous humour, while Rift Valley fever causes uveitis and chorioretinitis, and dengue and chikungunya are occasional causes of ocular disease.
Congenital ocular disease
Several congenital infections damage the developing eye.
| Virus | Congenital ocular features |
|---|---|
| Cytomegalovirus | Retinitis (chorioretinitis), cataract, optic atrophy |
| Rubella | Pigmentary retinopathy, cataract, glaucoma, microphthalmia |
| Varicella-zoster virus | Chorioretinitis, cataract, optic atrophy, microphthalmia |
| Herpes simplex virus | Ophthalmia neonatorum, keratitis, cataract, microphthalmia |
Congenital rubella is the classic cause of congenital ocular disease, producing cataract, a bilateral pigmentary (“salt and pepper”) retinopathy, glaucoma and microphthalmia; the diagnosis rests on demonstrating fetal rubella-specific IgM, present at birth. Congenital CMV is symptomatic in about 10% of neonates, a minority of whom have chorioretinitis or optic atrophy. Management of congenital rubella is directed at the complications, such as cataract and glaucoma surgery.
Diagnosis
Most ocular viral infections are diagnosed clinically, but laboratory confirmation guides treatment where the picture is atypical or sight is threatened. PCR of the appropriate ocular fluid is the most sensitive method, more so than culture or antigen detection, and intraocular antibody synthesis can be quantified by the Goldmann-Witmer coefficient (a value of 3 or more indicating local production against that virus).
| Virus | Specimen | Tests |
|---|---|---|
| HSV, VZV | Aqueous humour, biopsy | PCR, Goldmann-Witmer coefficient, culture |
| CMV | Vitreous, blood, biopsy | PCR, culture, serology and blood viral load |
| EBV | Blood, biopsy | PCR, serology |
| Adenovirus, enterovirus | Aqueous humour, conjunctival scrapings | PCR, culture |
| Rubella | Aqueous humour, blood, biopsy | PCR, Goldmann-Witmer coefficient, serology |
South African context
The country’s large HIV-affected population dominates the pattern of serious ocular viral disease. CMV retinitis is an important AIDS-defining illness in advanced immunosuppression, and the national HIV programme’s expansion of antiretroviral therapy is the main reason its incidence has fallen; fundoscopic screening is considered in patients with very low CD4 counts. Herpes zoster ophthalmicus is a common presentation of underlying HIV, particularly in younger adults. Measles remains a cause of childhood corneal blindness where vitamin A deficiency persists, so vitamin A is given in measles as both treatment and prophylaxis.
References and recommended reading
- Newman HM. Viral Disease of the Eye. In: Richman DD, Whitley RJ, Hayden FG, editors. Clinical Virology, 4th edition, Chapter 10. Washington: ASM Press; 2016. The backbone source for the ocular syndromes, the viral pathogens and their diagnosis and treatment.
- Burrell CJ, Howard CR, Murphy FA. Fenner and White’s Medical Virology, 5th edition. Academic Press / Elsevier; 2017. The source for the summary of viral infections of the eye.
- National Department of Health. National Consolidated Guidelines for the Management of HIV. Pretoria: NDoH; 2026. The South African reference for the management of HIV and its complications, including CMV disease.