Herpes Zoster Ophthalmicus

The brief prodrome of HZO consists of fever, malaise, and chills. The initial symptom is hyperesthesia or paresthesia, which may be severe, along the affected dermatome. This is followed by a maculopapular rash that becomes vesicular and finally pustular before crusting (Figure 9).

One common feature of HZO is severe eyelid edema that accompanies the rash and that can be mistaken for preseptal cellulitis. If the tip of the nose is affected by reactivation along the nasociliary nerve (as manifested by the appearance of cutaneous vesicles—the Hutchinson sign), there is almost always ocular involvement. Although the Hutchinson sign is a good rule of thumb, it is neither sensitive nor specific, and ocular involvement can occur in the absence of this sign.

Ocular zoster can affect any part of the eye from the conjunctiva to the optic nerve. It can cause keratitis, scleritis, uveitis, trabeculitis, choroiditis, acute retinal necrosis, optic neuritis, nerve palsies, and cavernous sinus thrombosis. Discussion of these noncorneal infections is beyond the scope of this module. Keratitis can be classified as acute or chronic/relapsing, both of which can lead to long-term sequelae.

Acute keratitis can occur up to 1 month following the onset of dermatitis. Some of the common manifestations include the following.

Punctate keratitis and pseudodendrites consist of swollen, poorly adherent epithelial cells and are usually seen in the corneal periphery and appear “stuck on” (Figure 10). In contrast to HSV dendrites, these pseudodendrites lack terminal bulbs and dichotomous branching and stain poorly with both fluorescein and RB. Although VZV has been cultured out of these lesions, they do not respond to topical antivirals.

Nummular keratitis is characterized by coin-shaped (nummular) lesions that appear in the superficial stroma. The lesions usually underlie areas of previous epithelial keratitis. They probably represent an immune-mediated stromal reaction to viral antigens.

HZO-related keratouveitis and endotheliitis resemble HSV keratouveitis and endotheliitis but are usually more severe, even leading to the development of a hypopyon or hyphema. Involvement of the trabecular meshwork can lead to severe glaucoma that may be unresponsive to glaucoma medications but responds to steroids.

Sclerokeratitis occurs as a crescent-shaped corneal infiltrate adjacent to an area of scleritis. It is clinically identical to nonherpetic peripheral ulcerative keratitis, and the etiology is thought to be limbal vasculitis and ischemia.

This form occurs up to several months following the initial HZO infection.

Mucous plaques can occur suddenly in an eye that has been nearly quiescent. They appear as stuck-on, grayish, branching lesions and have minimal underlying inflammation (Figure 11). Mucous plaques stain with RB, and they can be easily wiped off the cornea, leaving an underlying epithelium that is intact but poorly adherent. Therefore, they are thought to be a variant of filamentary keratitis, although some investigators have found viral DNA in the lesions. Mucous plaques can be highly resistant to treatment, and multiple recurrences can lead to scarring.

Disciform keratitis is similar to the disciform keratitis seen in HSK.

Interstitial keratopathy: HZO keratitis can lead to vascularization, with a leash of vessels leading up to the area of scarring. These vessels can exude large amounts of lipid that can cause significant corneal opacification.

As in HSV keratitis, neurotrophic ulcers can occur repeatedly and cause problems long after the acute episode has resolved. In contrast to HSV keratitis, however, profound loss of corneal sensation can result from a single episode of HZO, and these ulcers are more likely to perforate.

Herpes zoster can result in a persistent smoldering keratitis that may only manifest as a corneal haze with overlying epithelial irregularity. This can lead to progressive scarring and decrease in vision.

Neuralgia is almost always associated with acute HZO, but pain that lasts longer than 1 month constitutes postherpetic neuralgia (PHN), perhaps the most debilitating sequela of HZO. PHN occurs in 10% to 30% of patients with HZO, and its risk factors include increasing age, prodromal pain, more severe rash, greater acute pain, and ophthalmic involvement. The pain is of variable quality and has been described by patients as burning, shooting, sharp, throbbing, or tender. One classic feature of this pain is allodynia (pain following a stimulus that is normally non-noxious, such as wind). The pain can be severe and unrelenting and can take over the patient’s life, resulting in decreased functioning and increased risk of depression and suicide.

Topical antivirals have no role in the treatment of HZO. However, oral antivirals begun within 72 hours of onset of symptoms can reduce the severity of the disease and of any long-term complications, including PHN. Recent studies have indicated that in certain populations, such as immunocompromised patients, this 72-hour window can be extended. For every patient with HZO, oral acyclovir can be used, 800 mg 5 times a day, for 7 to 14 days, regardless of the stage of the disease, because the risks associated with use of this drug are low. Valacyclovir and famciclovir can also be used but are more expensive. For the treatment of HZO, a good rule of thumb is to double the doses of the medications used for HSV keratitis.

The use of corticosteroids for the treatment of HZO is controversial. Systemic corticosteroids have been shown to reduce the dermatitis and acute pain of HZO, but they do not have any effect on PHN. Also, their use may increase the risk of ocular complications such as mucous plaques and keratitis. Topical corticosteroids may be necessary for treating uncontrolled inflammation. However, once they are initiated, it is difficult to wean patients from them. Sudden discontinuation of corticosteroids may allow the suppressed inflammation to rebound; thus, corticosteroids must be tapered gradually to a level that minimizes the risk of rebound inflammation, but keeps the keratitis in check. The ophthalmologist should discuss with the patient the possibility that use of a mild steroid (fluorometholone or loteprednol, two to three times per week) may be necessary indefinitely, because complete tapering of ophthalmic corticosteroids is not always attainable.

As most long-term complications of HZO are related to the neurotrophic status and relative dryness of the affected eye, ocular surface support can decrease the risk of a poor outcome. Punctal occlusion, artificial tears, bandage contact lenses, tarsorrhaphy, eyelid reconstructive surgery, and conjunctival flaps all have a role to play in the treatment of the various HZO complications. Tarsorrhaphy is especially useful in recalcitrant cases of neurotrophic keratitis.

As the treatment of PHN is challenging and often frustrating for both the clinician and the patient, it is important to give the patient the following information: (1) in most cases, the pain associated with PHN resolves spontaneously (70% of those with pain at 1 month will be pain free at 1 year); and (2) treatment is able to “take the edge off” the pain, but unable to eliminate pain completely.

Table 2 summarizes the major types of drug therapy for PHN. Neurontin (gabapentin) has been shown to be effective in treating the pain as well as the sleep disturbance associated with PHN and was approved by the FDA for this indication. Recently, Lyrica (pregabalin) was approved by the FDA for the pain associated with PHN. Amitriptyline and nortriptyline have both an antidepressant effect and an analgesic effect, and the antidepressant activity appears to occur independently of the analgesic activity. Therapy is started at a low dose and titrated upward until pain relief occurs or adverse effects become intolerable. Opioids are used as a last resort but can be useful in intractable cases. Oxycodone is most commonly used. Capsaicin cream depletes substance P and is somewhat effective but causes significant burning. Topical lidocaine patches are now FDA-approved for PHN.