Acute retinal necrosis (ARN) is a medical inflammatory condition of the eye. The condition presents itself as a

necrotizing Necrosis () is a form of cell injury which results in the premature death of cells in living tissue by autolysis. Necrosis is caused by factors external to the cell or tissue, such as infection, or trauma which result in the unregulated dige ...

retinitis Retinitis is inflammation of the retina in the eye, which can permanently damage the retina and lead to blindness. The retina is the eye's "sensing" tissue. Retinitis may be caused by a number of different infectious agents. Its most common form, ...

. The

inflammation Inflammation (from la, wikt:en:inflammatio#Latin, inflammatio) is part of the complex biological response of body tissues to harmful stimuli, such as pathogens, damaged cells, or Irritation, irritants, and is a protective response involving im ...

onset is due to certain herpes viruses,

varicella zoster virus Varicella-zoster virus (VZV), also known as human herpesvirus 3 (HHV-3, HHV3) or ''Human alphaherpesvirus 3'' (taxonomically), is one of nine known herpes viruses that can infect humans. It causes chickenpox (varicella) commonly affecting chil ...

(VZV),

herpes simplex virus Herpes simplex virus 1 and 2 (HSV-1 and HSV-2), also known by their taxonomical names ''Human alphaherpesvirus 1'' and ''Human alphaherpesvirus 2'', are two members of the Herpesviridae#Human herpesvirus types, human ''Herpesviridae'' family, a ...

(HSV-1 and HSV-2) and

Epstein–Barr virus The Epstein–Barr virus (EBV), formally called ''Human gammaherpesvirus 4'', is one of the nine known human herpesvirus types in the herpes family, and is one of the most common viruses in humans. EBV is a double-stranded DNA virus. It is ...

(EBV). People with the condition usually display redness of the eye, white or off-white colored patches that are patches of retinal necrosis. ARN can progress into other conditions such as uveitis, detachment of the retina, and ultimately can lead to blindness. The disease was first characterized in 1971, in Japan. Akira Urayama and his colleagues had six patients whose cases showed signs of acute

, retinal

arteritis Arteritis is the inflammation of the walls of arteries, usually as a result of infection or autoimmune response. Arteritis, a complex disorder, is still not entirely understood. Arteritis may be distinguished by its different types, based on the ...

choroiditis Chorioretinitis is an inflammation of the choroid (thin pigmented vascular coat of the eye) and retina of the eye. It is a form of posterior uveitis. If only the choroid is inflamed, not the retina, the condition is termed choroiditis. The ophthal ...

, and late-onset retinal detachment. The combination of the conditions was given the name acute retinal necrosis. The first reports of ARN came about in 1971. It is unclear whether it was previously just reported as something else. Urayama and his colleagues reported the disease that they saw in six Japanese patients. Since then the disease has been seen in patient's with AIDS, children, and people who are

immunocompromised Immunodeficiency, also known as immunocompromisation, is a state in which the immune system's ability to fight infectious diseases and cancer is compromised or entirely absent. Most cases are acquired ("secondary") due to extrinsic factors that a ...

. In 1978, Young and Bird named the disease when presented in both eyes, Bilateral Acute Retinal Necrosis, otherwise known as BARN.

Signs and symptoms

Patients with ARN typically present *

floater Floaters or eye floaters are sometimes visible deposits (e.g., the shadows of tiny structures of protein or other cell debris projected onto the retina) within the eye's vitreous humour ("the vitreous"), which is normally transparent, or between ...

s * redness of the eye * flashes * decreased sharpness of vision *

photophobia Photophobia is a medical symptom of abnormal intolerance to visual perception of light. As a medical symptom photophobia is not a morbid fear or phobia, but an experience of discomfort or pain to the eyes due to light exposure or by presence of ...

. Though uncommon, some patients may experience pain. Most patients will only experience this in one eye (unilateral), though possible for the condition to be seen in both (bilateral, BARN). If the first eye is left without treatment, some cases have shown the disease progressing to the other eye in a month's time. Further progressed stages of the disease can cause blindness in the eye experiencing ARN. Though the disease may be present itself, the inflammation of the retina may not been visualized for decades after the initial signs.

Causes

ARN is associated with people who have latent herpes viruses that have been reactivated. The most common causes of the disease have been linked to VZV, HSV-1, HSV-2, and CMV respectively. ARN cases have been reported in patients who have AIDS, are immunocompromised and in children. The disease is not limited to a specific gender. Most cases have been reported in young adults though children and the elderly can be affected. Specific genetic markers in Caucasians in the United States have shown elevated risk for disease development (HLA-DQw7 and Bw62, DR4) as well as HLA-Aw33, B44, and DRw6 in the Japanese population.

Pathophysiology

ARN presentation in individuals can be characterized by two separate phases as listed below.

Acute Herpetic Phase

The acute herpetic phase is characterized by when viral particles infiltrate the retina and

vitreous Vitreous may refer to: Materials * Glass, an amorphous solid material ** Vitreous enamel, a material made by fusing powdered glass to a substrate by firing * Vitreous lustre, a glassy luster or sheen on a mineral surface Biology * Vitreous body, ...

causing an inflammatory reaction. Together, the viral particles and mononuclear cells in the vitreous cause the retina to become opaque. In response to all this,

lymphocyte A lymphocyte is a type of white blood cell (leukocyte) in the immune system of most vertebrates. Lymphocytes include natural killer cells (which function in cell-mediated, cytotoxic innate immunity), T cells (for cell-mediated, cytotoxic ad ...

s and

plasma cell Plasma cells, also called plasma B cells or effector B cells, are white blood cells that originate in the lymphoid organs as B lymphocytes and secrete large quantities of proteins called antibodies in response to being presented specific sub ...

s diffuse into the vitreous as well.

Late Cicatricial Phase

The late

cicatricial A scar (or scar tissue) is an area of fibrous tissue that replaces normal skin after an injury. Scars result from the biological process of wound repair in the skin, as well as in other organs, and tissues of the body. Thus, scarring is a nat ...

phase of ARN includes changes in the way the vitreous is organized due to the

cellular infiltration Infiltration is the diffusion or accumulation (in a tissue or cells) of foreign substances in amounts excess of the normal. The material collected in those tissues or cells is called infiltrate. Definitions of infiltration As part of a disease ...

seen in the previous phase. In the vitreous and on top of the thinned necrotic retina, contractile membranes may form. If left untreated, 50 to 75% of patients with ARN will experience detachment of their retina in the affected eye.

Diagnosis

Diagnosis of ARN is outlined by the American Uveitis Society. Though most diagnoses of ARN are made by clinical features, a physician may take a vitreous sample and have it tested for herpes markers. Common lab tests that are run on the sample include a viral culture, viral PCR, direct/indirect immunofluorescence, viral antibody measurement. The American Uveitis Society has established the following guidelines for ARN diagnosis: # Retinal necrosis with one or more focus points borders in the peripheral retina # In the absence of antiviral treatment, the condition progresses rapidly # Spreading to the surroundings # Buildup of blood vessels # Inflammation of the vitreous.

Prevention

While there is no prevention for ARN, exposing a patient to antiviral agents in the earlier phases of the outbreak tend to decrease the duration of the active phase of the disease. Taking antiviral agents after the issue is resolved seems to lessen the chance of it spreading to the other eye.

Treatment

Medication

Currently treatment of ARN consists of

antiviral therapy Antiviral drugs are a class of medication used for treating viral infections. Most antivirals target specific viruses, while a broad-spectrum antiviral is effective against a wide range of viruses. Unlike most antibiotics, antiviral drugs do no ...

administered orally. Typical antiviral agents used include famciclovir, valganciclovir, and valacyclovir. While on these medications, a patient's kidney function should be watched. Some physician's also may administer the antiviral agents via intravitreal delivery. Though controversial, some physicians administer steroids (prednisone) and antithrombotic therapy (aspirin). Some commonly administered antiviral agents are as follows: *

Acyclovir Aciclovir (ACV), also known as acyclovir, is an antiviral medication. It is primarily used for the treatment of herpes simplex virus infections, chickenpox, and shingles. Other uses include prevention of cytomegalovirus infections following tra ...

Famciclovir Famciclovir is a guanosine analogue antiviral drug used for the treatment of various herpesvirus infections, most commonly for herpes zoster (shingles). It is a prodrug form of penciclovir with improved oral bioavailability. Famciclovir is marke ...

Valacyclovir Valaciclovir, also spelled valacyclovir, is an antiviral medication used to treat outbreaks of herpes simplex or herpes zoster (shingles). It is also used to prevent cytomegalovirus following a kidney transplant in high risk cases. It is taken ...

* Gancicilovir *

Valganciclovir Valganciclovir, sold under the brand name Valcyte among others, is an antiviral medication used to treat cytomegalovirus (CMV) infection in those with HIV/AIDS or following organ transplant. It is often used long term as it only suppresses r ...

Research

In a study done published by the British Journal of Ophthalmology, the cases of ARN/BARN reported in 2001-2002 in the UK, Varicella Zoster Virus was the most common culprit for the disease and presented mostly in men than in women. Researchers have also looked at two cases of ARN in patients who have been diagnosed with an immunodeficiency virus. The disease presented itself more so in the outer retina until it progressed far enough to then affect the inner retina. The patients were not so responsive to the antiviral agents given to them through an IV, acyclovir specifically. The cases progressed to retinal detachment. The patients tested positive for the herpes virus. Researchers are now wondering if this type of ARN is specific to those who have the immunodeficiency virus.

References

External links

{{Medical resources , DiseasesDB = 4973 , ICD10 = H35.89 , ICD9 = {{ICD9, 362.89 , ICDO = , OMIM = , MedlinePlus = , eMedicineSubj = oph , eMedicineTopic = 377 , MeshID = D015882 Disorders of choroid and retina Varicella zoster virus-associated diseases Herpes simplex virus–associated diseases