Herpes Simplex Uveitis
Herpes simplex virus (HSV) associated uveitis is a common cause of unilateral hypertensive anterior uveitis. Herpetic anterior uveitis causes approximately 5-10% of uveitis cases.
Herpes simplex iritis is due to the Herpes simplex virus. The most common subtype is HSV-1. It can lay dormant in the trigeminal ganglion and becomes reactivated that manifests as skin lesions, keratitis, or anterior uveitis. Anterior uveitis is more common during reactivation vs primary disease.
HSV associated anterior uveitis is more common in patients in their 40-50's affecting both genders equally.
Patients may have a medical history of cold sores or fever blisters. 
Herpes simplex virus in a double stranded DNA virus and can be separated in two types: HSV-1 and HSV-2. HSV-1 commonly is the cause of mouth ulcers or cold sores and HSV-2 is responsible for genital herpes. Infections are caused by contact with an infected individual at times of reactivation.
There is no evidence of primary prevention strategies for HSV iritis or ocular HSV.
Clinical Findings / Signs
Keratouveitis and iritis are uncommon manifestations of primary HSV ocular infection. In a study of a large population in the Northern California region of Kaiser Permanente, iritis was the presenting sign in 1% of patients with an initial episode of HSV eye disease.[ref.]
Most commonly, in patients with iritis due to HSV, a keratouveitis is present. Findings in those cases may include a combination of these findings: (from anterior to posterior) corneal epithelial and/or stromal edema, stromal keratitis, keratic precipitates, endothelitis, and anterior chamber cells and flare. Iritis can also occur alone, without evidence of keratitis, and may present as an unilateral hypertensive anterior uveitis.
Keratic precipitates (KP) may take several forms. They can be granulomatous, nongranulomatous, or stellate. Often they may be present in a patch on the endothelial surface, underlying a localized patch of corneal edema. They can be regional, in the inferior one-third of the cornea or diffuse. When stellate KP are present, they are typically diffuse. [BCSC] High intraocular pressure is a common complication of HSV iritis and can serve as a diagnostic hallmark. [Table of acute iritis and high IOP] The IOP can be very high, in the range of 50-60 mm Hg during an episode of acute iritis. High IOP is due to trabeculitis, as well as inflammatory cells clogging the trabecular meshwork. Although antiglaucoma therapy may be required in the acute setting, once the inflammation is controlled, typically the intraocular pressure will normalize and the patient will not require ongoing antiglaucoma treatment. Other signs include posterior synechiae and iridoplegia. 
Spontaneous hyphema can occur in HSV iritis, as well as layers of hyphema mixed with hypopyon, known as a “candy-cane hypopyon”.
Although patchy iris atrophy may be present following an episode of HSV keratouveitis or iritis, inflammatory iris lesions are not typically seen. Disease is more common a unilateral process, but can be bilateral as well.
Typical symptoms of iritis with photophobia and pain are seen in HSV iritis. If there is an accompanying high IOP, headache, deeper pain, and decreased vision due to corneal edema may be present. In patients with keratouveitis, pain and decreased vision may be present because of the keratitis and edema. If there is significant damage to CN 5, from prior episodes of HSV, the patient may not have significant pain.
The diagnosis of HSV iritis is suggested by a unilateral anterior uveitis, accompanied by high intraocular pressure. The presence of patchy iris transillumination defects further suggests HSV iritis, but the absence of transillumination defects does not rule it out. A prior history of HSV ocular disease is also strongly suggestive of the role of HSV in iritis. Other suggestive features are cornea hypoesthesia and the appearance of the keratic precipitates.
Diagnostic procedures / Laboratory Testing
Because of the high prevalence of positive HSV antibodies in most populations, serology is only helpful in the diagnosis in that a negative HSV antibody titer will rule out the possibility that iritis is due to HSV. Polymerase chain reaction for HSV DNA from an anterior chamber tap may be helpful in diagnosis with a high sensitivity (91.3%) and specificity (98.8).
Topical corticosteroids are the mainstay of treatment for HSV iritis. Cycloplegic agents may be helpful to decrease symptoms of photophobia and decrease or lyse posterior synechiae.
Topical antiviral agents may help to prevent dendritic keratitis during treatment with corticosteroids, in patients with keratouveitis. In general topical antivirals are of little use in the treatment of HSV iritis, since these agents do not penetrate well into the anterior chamber. In fact, topical antiviral agents may be detrimental due to their topical toxicity. Systemic antiviral agents, such as acyclovir, famcyclovir, or valacyclovir, attain excellent anterior chamber drug levels and may be beneficial in cases of iritis. The HEDS study’s [link to HEDS page] trial of acyclovir in the treatment of HSV iritis was stopped prior to meeting the number of subjects needed according to the sample size estimates. This was done because of problems with recruitment. In the findings that were published, there was a statistically suggestive trend for more rapid resolution of iritis with the use of systemic acyclovir, 400 mg five times per day.
Appropriate doses of systemic antiviral agents for treating active ocular disease are: acyclovir, 400 mg five times per day; valacyclovir, 1000 mg three times per day; famciclovir 250 mg three times per day.
Local injections or systemic corticosteroids are not typically required for control of inflammation.
Some patients may require very slow tapering of topical corticosteroids and may require long term, low dose topical corticosteroid therapy to control inflammation.
Long term, low dose, systemic antiviral therapy may be beneficial for some patients, in order to decrease the frequency of recurrences of iritis. At present, controlled studies to show this are lacking. One might expect the HEDS study findings on prophylaxis may be generalizable to iritis, but this cannot be certain given the low number of strictly iritis patients. Oral doses for prophylaxis for ocular herpes simplex disease are acyclovir, 400 mg twice per day or valacyclovir, 500-1000 mg daily.
There are no surgical treatments for HSV iritis. If adequate medical management of high intraocular pressure is not possible, glaucoma surgery may be occasionally needed. One should keep in mind, however, that in most patients, the intraocular pressure will significantly improve once inflammation is controlled.
- Rathinam SR. Global variation and pattern changes in epidemiology of uveitis cases. Indian J Ophthalmol. 2007;55:173–183
- Chan NS, Chee SP. Demystifying viral anterior uveitis: A review. Clin Exp Ophthalmol. 2019 Apr;47(3):320-333. doi: 10.1111/ceo.13417. Epub 2018 Nov 13. Review. PubMed PMID: 30345620.
- Chan NS, Chee SP. Demystifying viral anterior uveitis: A review. Clin Exp Ophthalmol. 2019 Apr;47(3):320-333. doi: 10.1111/ceo.13417. Epub 2018 Nov 13.Review. PubMed PMID: 30345620.
- Sugita S, Ogawa M, Shimizu N, et al. Ophthalmology. 2013;120:1761–1768.
- Acyclovir for the prevention of recurrent herpes simplex virus eye disease. Herpetic Eye Disease Study Group. N Engl J Med. 1998 Jul 30;339(5):300-6. PubMed PMID: 9696640.