Acute retinal necrosis (ARN) is a rare development occurring after a viral infection. Statistically, there are only about 0.63 cases in every one million people, and ARN accounts for 5.5% of all cases of uveitis, which is inflammation in the part of the eye called the uvea leading to vision loss. Most symptoms begin occurring in individuals between the ages of 20-50 years old, with HSV-related onset more common in young adults (age 20-30) and VZV-related onset more common in older adults (age 50+). 

While the exact mechanism is unknown, acute retinal necrosis (ARN) occurs when a dormant viral infection is reactivated and causes inflammation in the retina and connective tissue. The following viral infections have been reported to cause cases of ARN: herpes simplex virus 1 (HSV-1), herpes simplex virus 2 (HSV-2), cytomegalovirus, Epstein-Barr virus (EBV), or varicella-herpes zoster virus (VZV). ARN occurs in individuals without immunodeficiency, but some cases have been caused by immunogenetic predisposition, when the body cannot express certain antibodies that recognize and destroy antigens released by HSV and VZV viruses. The use of immunosuppressants can also lead to the development of ARN, for when the body’s immune response is dampened to prevent autoimmune effects it is less equipped to fight off a dormant infection. ARN may start to develop years after a viral infection or follow a particularly aggressive case. While the exact mechanism is unknown, acute retinal necrosis (ARN) occurs when a dormant viral infection is reactivated and causes inflammation in the retina and connective tissue. The following viral infections have been reported to cause cases of ARN: herpes simplex virus 1 (HSV-1), herpes simplex virus 2 (HSV-2), cytomegalovirus, Epstein-Barr virus (EBV), or varicella-herpes zoster virus (VZV). ARN occurs in individuals without immunodeficiency, but some cases have been caused by immunogenetic predisposition, when the body cannot express certain antibodies that recognize and destroy antigens released by HSV and VZV viruses. The use of immunosuppressants can also lead to the development of ARN, for when the body’s immune response is dampened to prevent autoimmune effects it is less equipped to fight off a dormant infection. ARN may start to develop years after a viral infection or follow a particularly aggressive case.

Individuals with ARN report a range of symptoms and varying degree of vision loss. The following symptoms, while common in other retinal disorders or uveitis diseases, have been reported in cases of ARN:

• Red eyes and inflammation

• Pain surrounding the exterior of the eye

• Hazy vision or decreased vision

• Appearance of floaters in vision

• Decreased color vision

There are varying degrees of severity and vision loss associated with ARN that describe the stages of the disease. Stage 1 is described as necrotizing retinitis, described as having slight peripheral vision loss and pressure behind the eyes. Stage 2, or vitreous opacification, starts to cause vision loss as the vitreous gel-like solution in the back of the eye that allows light to pass through becomes clouded. Stage 3 is regression of retinal necrosis, with more damage to retinal cells and cloudiness of the vitreous solution. Stage 4 is full retinal detachment, in which the retina cells become detached from the rest of the eye and can cause complete loss of vision and require surgery or cause irreparable damage to the eye.

An ophthalmological examination is necessary for a diagnosis of ARN, usually conducted by a pupil dilation and examination of the peripheral retina at the back of the eye for evidence of whitening or vasculitis (clear liquid turning opaque). A diagnosis of ARN is confirmed upon observing the following four features in the eye:

1. At least one peripheral retinal necrosis (flat and white pigment in the retina) with well-defined borders

2. Rapid progression of necrosis when antiviral therapy is not administered

3. Occlusive vasculopathy, or inflammation of the blood cells of the retina and decrease blood flow

4. Prominent vitreous and anterior chamber inflammation in the eye with the vitreous taking on an opaque appearance

To confirm ARN, various diagnostic tests are utilized. Fundoscopy and fluorescein angiography help visualize retinal changes, while polymerase chain reaction (PCR) testing of aqueous or vitreous samples can identify the viral DNA. A blood sample or sample of cerebrospinal fluid is analyzed by PCR to check for HSV or VZV viruses. Optical coherence tomography (OCT) and ultrasonography are additional tools that provide detailed imaging of retinal layers and the vitreous.

The primary treatment for acute retinal necrosis involves antiviral medications to remove the viral infection from the body that is causing inflammation in the eye. During early stages of ARN, antiviral therapy is prescribed, generally using one or a combination of the following drugs: intravenous acyclovir, oral valacyclovir, oral famciclovir, intravitreal foscarnet, intravitreal valacyclovir, or intravitreal famciclovirm. Treatment generally follows prescribing a short term oral agent for 1 week followed by a longer term oral prescription for 6 months to prevent infection. In cases of late stage ARN, especially when retinal detachment has occurred or when eyesight has been extremely affected, other surgeries can be performed to rescue eyesight. A virectomy surgery targets the vitreous in the eye, which is a gel-like substance that allows light to pass through and reach the retina. In ARN, the vitreous can become cloudy, and a virectomy removes the cloudy vitreous and replaces it with clear silicone oil. A laser known as endolaser can be used to repair damage to the retina with laser accuracy and to reattach it in cases of retinal detachment.

Zostavax, a vaccine available to prevent infection by herpes zoster (or varicella zoster virus VZV) can be administered to lower the risk of infection. There have been cases of acute retinal necrosis that occur after Zostavax vaccination, however symptoms are often less severe. There have been very rare cases of the Zostavax vaccine causing ARN to develop, however these cases were immuno-compromised individuals who likely had dormant virus that was activated with the live vaccine. 

The prognosis of acute retinal necrosis depends on the stage and degree of damage that inflammation has inflicted on the retina. The disease progression of ARN can be slowed or even halted if detected early. Prescribing antiviral therapy has been shown to significantly reduce loss of vision and other complications including risk of retinal detachment, and maintaining consistent use of these antiviral medications can stabilize vision. Retinal detachment is the most severe complication associated with ARN, and can lead to total blindness in one or both eyes if affected. Prompt diagnosis and early treatment of ARN decreases this risk and improves vision outcomes. Once lost due to ARN, the retinal cells cannot be replaced and vision remains in its worsened state.

1. https://emedicine.medscape.com/article/1223047-clinical?form=fpf

2. https://www.aao.org/eyenet/article/diagnosis-and-treatment-of-acute-retinal-necrosis

3. https://eyewiki.aao.org/Acute_Retinal_Necrosis

4. https://www.nature.com/articles/s41433-024-03028-x

5. https://www.frontiersin.org/journals/ophthalmology/articles/10.3389/fopht.2022.916113/full

6. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8871417/

7. https://www.ncbi.nlm.nih.gov/books/NBK470588/ 

8. https://www.hopkinsmedicine.org/health/wellness-and-prevention/vitrectomy#:~:text=What%20is%20vitrectomy%3F,back%20part%20of%20your%20eye. 

9. https://www.vrmny.com/procedures/endolaser-retinopexy-endoscopy/ 

10. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5597443/#:~:text=Discussion,the%20severity%20of%20the%20ARN.