Herpes Zoster Ophthalmicus: A Review

Herpes zoster is caused by reactivation of varicella zoster virus. When primary infection by varicella during childhood (chickenpox) is resolved, the virus particles remain as a dormant in the dorsal root or other sensory ganglion for many decades. The virus then reactivates as a result of aging, excessive stress, immunosuppressive illness, or other medical treatment that suppress the immunity. This reactivation of latent varicella zoster causes herpes zoster.

Herpes zoster ophthalmicus (HZO) involves the ophthalmic branch, which is the first division of the trigeminal nerve. According to several studies ophthalmic division of the trigeminal nerve are involved in about 10-25% of reported cases of herpes zoster cases. Zoster ophthalmicus is estimated to occur approximately in 10% of zoster patients under the age of 10 years and about 30% of patients aged 80-year-old and older. Thus patients older than 50 years of age are frequently at increased risk of that HZO [1]. The rash of ophthalmic zoster may extend from the level of the eye to the vertex of the skull and does not cross the midline of the forehead.

Signs and Symptoms of Herpes zoster ophthalmicus

Influenza-like illness with malaise and low-grade fever are common at the start of HZO that lasts up to 5 days before the appearance of rash on the forehead, eyelids and periorbital region. Subsequently, erythematous macules appear along the involved dermatome, rapidly progressing to papules and vesicles containing clear serous fluid and pustules over several days. Then finally these lesions rupture and get crusted. The eye very rarely gets involved when the maxillary branch of nerve is involved. Involvement of the nasociliary branch of the ophthalmic nerve which is evidenced by a zosteric rash on the tip and side of the nose (Hutchinson’s sign) is seen in about one-third of patients HZO and is usually accompanied by ocular symptoms. Thus, when ophthalmic zoster affects the side and the tip of the nose, careful attention must be given to the condition of the eye and immediate ophthalmologic consultation is necessary in order to prevent complications of the eye and central nerve system Zoster Infection.

Herpes Zoster Ophthalmicus

Herpes Zoster Ophthalmicus

The reactivated VZV travels down the ophthalmic nerve ganglion resulting in HZO. It takes about 3-4 days for the virus to reach the nerve ending. Nasociliary branch innervates both the tip and the homolateral side of the nose as well as the cornea so most serious ocular involvement will develop if this branch is affected. Hutchinson’s sign is classical sign representing the involvement of ocular structures. VZV-DNA was detected in conjunctival swabs of some cases of acute ophthalmic zoster disease [2]. All the patients who develop herpes zoster adjacent to eye do not develop ocular involvement, but in those that do, there can be a wide variety of manifestations.

Acute Stage of Ocular Involvement

Besides pain and rash in the affected ophthalmic dermatome other acute stage ocular involvement includes swelling and reddening of eye, ptosis with some even developing blepharitis and vesicular lesions which mostly resolves with scarring. Conjunctivitis is also common finding usually presents with the appearance of rash and resolves within 1 week. Episcleritis and scleritis are also not uncommon and involvement of cornea occurs if the condition lasts more than 1 week. Keratitis is another common presentation which occurs in various forms e.g. nummular keratitis and disciform keratitis and is detected about 10–21 days after onset of rash. There is also a stromal haze surrounding the lesions. Anterior uveitis which is also quite frequently seen develops 2 weeks after the onset of rash, can result in iris atrophy due to sever inflammation of rash. Also endothelial dysfunction of the cornea may occur leading to edema with central vision loss [3].

Chronic Stage of Ocular Involvement

Chronic involvement of sclera and cornea is much more common than the acute clinical findings. Stromal keratitis which may develops after 3-4 months of initial onset of disease is characterized by infiltrates of differing degree and is usually localized in the center of cornea. Keratitis may finally result in neurotrophic keratopathy. Corneal thinning with bullous keratopathy and corneal perforation may also lead to vision loss.

Acute retinal necrosis syndrome (ARN) and progressive outer retinal necrosis syndrome (PORN) are almost very rare findings in young patients. ARN and PORN are characterized by pain and blurred vision in one or both eyes (30% bilateral involvement). Clinically the fundus of ARN shows whitening and peripheral patches with occlusive vasculitis and vitreous inflammation. In case of PORN, vitreous cells are absent as immunocompromised individuals are not able to produce an inflammatory response. In such cases even early course of antiviral therapy may not work and may lead retinal detachment in about 70% of the cases.

Recent study has reported several ocular manifestations of HZO. Pain was the most presenting symptoms in all individuals. Eyelid and ocular adnexal involvement is most commonly seen in patients with herpes zoster ophthalmicus followed by conjunctivitis, corneal complication, uveitis and PHN. As HZO may cause visual loss, regular ophthalmic examination is very important.

Treatment of Herpes Zoster Ophthalmicus

Beside, commonly used antivirals agents for herpes zoster like acyclovir, Famciclovir, valacyclovir, and brivudin, immediate use of a single intravitreal injection of foscarnet is usually recommended to further stop viral replication and progression to retinitis especially in case of ARN or PORN [4]. Systemic steroids are generally recommended for immunocompetent patients and those over 60 years of age but are strictly contraindicated in immunocompromised individuals at any age. Oral antiviral agents when given early have better prognosis and in management to PHN. Study shows that, Brivudin [5] had an 11% lower PHN rate than acyclovir and was as seen as effective as famciclovir to reduce zoster associated pain. In case of resistance to common antivirals agents, intravenous foscarnet, 40 mg/ kg body weight 3 times a day or 50 mg/ kg body weight twice a day is recommended. Treatment with cidofovir is recommended in case of resistance with intravenous foscarnet. These two antiviral agents should only be given in special cases when required as they have severe side effects like nephrotoxicity, ocular hypotony etc.

References:
[1] Hardening SP, Lipton JR, Wells JCD: Natural history of herpes zoster ophthalmicus: predictors of postherpetic neuralgia and ocular involvement. Br J Ophthalmol 1987:353–358.
[2] Zaal MJW, Völker-Dieben HJ, Wienesen M, DÀmaro J, Kijlstra A: Longitudinal analysis of aricella-zoster virus DNA on the ocular surface associated with herpes zoster ophthalmicus. Am J Ophthalmol 2001:25–29.
[3] Zaal MJW, Völker-Dieben HJ, DÁmaro J: Visual prognosis in immunocompetent patients with herpes zoster ophthalmicus. Acta Ophthalmol Scand 2003:216–220.
[4] Gümbel H, Ohrloff C: Opportunistic infections of the eye in immunocompromised patients. Ophthalmologica 1997:53–61.
[5] Vij O, Bornfeld N, Roggendorf M, Fiedler M, Schilling H: Brivudin as an alternative systemic therapy to acyclovir and ganciclovir in acute retinal necrosis syndrome due to varicella zoster virus. Klin Monatsbl Augenheilkd 200:710–715.

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