The clinical picture of HZO is best described according to the phases of the disease.

Prodrome

Approximately 60% of patients experience the prodromal phase, in which they feel tingling and pain in the forehead. Additionally, this stage consists of flu-like symptoms such as fever, malaise, and myalgia, typically lasting for a week. 

Acute

The acute stage features a painful unilateral rash in a dermatomal pattern on the forehead representing the affected subdivision(s) of the ophthalmic nerve (supraorbital, lacrimal, and nasociliary). The rash is initially erythematous and macular in appearance. Over the next few days, the rash rapidly transforms into papules, vesicles, and pustules. Then they rupture, crust, scab and ultimately heal over several weeks [6]. Additionally, marked ocular pain and edema of the eyelid are commonly observed. These two can result in blepharitis, which subsequently causes ptosis. Further, most patients will have an accompanying rash on the eyelid, in which the vesicles heal and leave behind little scarring.

Further conditions may include photophobia, conjunctival hyperemia (circumcorneal or episcleral), corneal edema, keratitis, and uveitis. Moreover, conjunctivitis is frequently found in patients with HZO. Cornea diseases can impair vision and are observed in 65% of patients with HZO [5]. Anterior uveitis can occur individually or coexist with keratitis. These latter two conditions lead to scarring. In patients with HZO, Hutchinson’s sign is strongly associated with ocular presentation. However, even patients who do not exhibit this clinical sign can have ocular features [7].

Late sequelae

The later phase of HZO includes scarring and excessive blood vessel growth in the cornea. Additionally, eye diseases such as glaucoma, cataract, and chronic uveitis can occur. All of these may result in loss of vision. Another late complication, postherpetic neuralgia, may also develop especially if HZO is not treated early. In immunocompromised patients, the vesicular rash is followed by profound illness within one or two weeks. 

• Inflammation

  This case report discusses the correlation of HAART induction with immune recovery and ocular inflammation in an HIV-positive patient with a history of herpes zoster ophthalmicus (HZO). [ncbi.nlm.nih.gov]

  […] with various symptoms of acute orbital inflammation before eruption of a vesicular rash. [j-nn.org]

  Serious sequelae include chronic ocular inflammation, vision loss, and disabling pain. [aafp.org]

• Swelling

  Drooping and severe swelling of the left eyelid were present, along with keratitis and uveitis. While the lid swelling and uveitis were improving, external ophthalmoplegia and exophthalmos were discovered. [ncbi.nlm.nih.gov]

  On repeated examination, it was noted that the patient had swelling of the left upper eyelid, conjunctival congestion, restricted abduction of the left eye, which is diagnostic of a left sixth cranial nerve palsy (right, center, and left gaze; Panels [nejm.org]

  […] tissue (arrowhead), enlargement of the lacrimal gland (arrow) and (C) swelling of the right superior rectus and medial rectus muscles (arrows). [j-nn.org]

• Constitutional Symptom

  Additionally, the herpetic rash may be preceded by constitutional symptoms such as fever, fatigue, malaise, and headaches. The presence of herpetic lesions around the tip of the nose is known as the Hutchinson sign. [ncbi.nlm.nih.gov]

• Chills

  Flu-like illness with fatigue, malaise, and low grade fever and chills that last up to one week before the rash over the forehead appears Pain: usually non-painful actions, like putting on a hat and combing hair may be very painful in about 60% of patients [ispub.com]

  Additional symptoms may include abdominal pain, chills, fever, joint pain, taste and vision problems, headaches or even loss of eye motion or a drooping eye. [ozarkderm.com]

  Other symptoms may include: Fever and chills General ill feeling Headache Joint pain Swollen glands (lymph nodes) You may also have pain, muscle weakness, and a rash involving different parts of your face if shingles affects a nerve in your face. [nlm.nih.gov]

  Prodromal Stage Flu-like illness with fatigue, malaise, and low grade fever and chills that last up to one week before the rash over the forehead appears Pain: usually non-painful actions, like putting on a hat and combing hair may be very painful in [cehjournal.org]

  People with shingles may also experience: Headache Fever Chills Loss of appetite Read more about Signs of Shingles » Causes of herpes zoster ophthalmicus Only those who have previously had chickenpox are at risk of developing shingles or ophthalmic shingles [ada.com]

• Pallor

  Fundus examination of the left eye showed a temporal pallor of the optic disc (Figure). [ijo.in]

• Erythema

  A 78-year-old man initially presented with patchy erythema and herpetiform vesicles on his left forehead and upper eyelid. [ncbi.nlm.nih.gov]

  Case presentation A 78-year-old man initially presented with patchy erythema and herpetiform vesicles on his left forehead and upper eyelid. [bmcinfectdis.biomedcentral.com]

  History and Clinical Examination A 2.5-year-old boy presented with acute onset of a vesicular rash involving the left forehead with swelling and erythema of the left upper eyelid since day 1. [academic.oup.com]

• Macula

  Dilated examination of the lens, macula, peripheral retina, optic nerve, and vitreous. Signs Erythematous skin lesions with macules, papules, vesicles, pustules, and crusting lesions in the distribution of the trigeminal nerve. [eyewiki.aao.org]

• Anterior Uveitis

  However, anterior uveitis, necrotizing scleritis, secondary glaucoma, and corneal dellen developed during follow-up. At the ninth month, pericardial patch graft (Tutoplast) was placed due to progression of the scleral thinning. [ncbi.nlm.nih.gov]

  Visual prognosis is good, especially in patients who have only anterior uveitis without corneal disease. [dx.doi.org]

  […] usual adult dose, for acute or recurrent zoster-associated anterior uveitis. [jmedicalcasereports.biomedcentral.com]

• Eye Pain

  A 47-year-old woman with acute retrobulbar eye pain and diplopia preceding the vesicular rash of herpes zoster ophthalmicus was evaluated and treated. [ncbi.nlm.nih.gov]

  The patient presented with 1 week of right-sided eye pain associated with swelling, white discharge, and ulcerative papules involving the surrounding skin. [ingentaconnect.com]

  Herpes zoster ophthalmicus is a reactivation of a varicella-zoster virus infection (shingles—Herpes Zoster) involving the eye. It is characterized by eye pain, a Zoster rash on the forehead, and eyelid swelling and inflammation. [patientslikeme.com]

  In addition to vision loss, other complications include increased pressure within the eye and chronic pain. [drugtopics.com]

  A 51-year-old woman presented to the hospital with severe left eye pain and a diffuse vesicular rash around the left eye and on the forehead. History and physical examination. [consultant360.com]

• Corneal Opacity

  Corneal ulcer and skin lesions were healed, but the patient developed cicatricial ectropion of right upper lid and best corrected visual acuity of right eye was reduced to 6/60 due to corneal opacity. [ncbi.nlm.nih.gov]

  Ocular complications included neurotrophic keratopathy (1.9%), corneal opacity (5.9%), secondary glaucoma (7.8%), optic atrophy (1.9%), and postherpetic neuralgia (13.3%). Mean follow-up was 12 months. [joii-journal.springeropen.com]

  Clinical follow-up of phototherapeutic keratectomy for the treatment of corneal opacities. Am J Ophthalmol. 1993; 115: 433-440 Sher N.A. Bowers R.A. Zabel R.W. et al. Clinical use of the 193-nm excimer laser in the treatment of corneal scars. [aaojournal.org]

  This is considered a prognostic sign of sight-threatening ocular complications. [16] Although the tip of the nose was spared in the case being reported, she developed severe keratoconjunctivitis with corneal opacity and upper lid ectropion. [nigerianjournalofophthalmology.com]

  They include dendritic keratitis, secondary corneal anaesthesia, persistent epithelial defect, secondary infection, stromal neovascularisation, and corneal opacity (Figure 1). [cehjournal.org]

• Conjunctival Injection

  The ophthalmic exam evidences severe ciliary and conjunctival injection, dendritic keratitis, corneal endothelial plaques and positive Hutchinson's sign. [medigraphic.com]

  Adnexal involvement, including lid edema, blepharoconjunctivitis with macular rash involving the eyelids, conjunctival injection, vesicles, and petechial hemorrhages, was sought. [joii-journal.springeropen.com]

  Biomicroscopy OS revealed worsening lid swelling/ptosis of the left lid, 2–3+ conjunctival injection, 3–4+ diffuse corneal punctate epithelial erosions (staining with both lissamine and NaFl), dark and quiet anterior chamber, clear iris, and moderate [journalofoptometry.org]

• Corneal Infiltrate

  These epithelial lesions can lead to anterior stromal corneal infiltrates. [cehjournal.org]

  […] by multiple fine granular infiltrates in the anterior corneal stroma below the epithelial layer (Figure 3). [aafp.org]

• Neuralgia

  The correlation of eruption severity and distribution with ocular complications, visual outcome and postherpetic neuralgia was statistically evaluated. [ncbi.nlm.nih.gov]

  Six weeks later, he had minimal residual diplopia, with no postherpetic neuralgia. It is important that this diagnosis be made early, to minimize complications such as corneal ulceration and uveitis, which may threaten vision. [nejm.org]

  If this pain persists for longer than one month after the rash has healed, it is termed post-herpetic neuralgia. [geekymedics.com]

• Burning Sensation

  CaseA 35 year old man presented with Fever - 4days Burning sensation on forehead and around left eye - 2 days Vesicular eruptions - 1 day Discharge (LE) - 1 day DV (LE) - 1 day 3. [slideshare.net]

  However, it is not uncommon for a painful burning sensation to linger in the area of the skin rash for months or even years. [provisu.ch]

• Hyperesthesia

  HZO begins with a prodrome of severe burning or lancinating pain, dysesthesia or hyperesthesia over the affected dermatome, mild fever, nausea, and malaise (Fig. 5). The preeruptive pain may be insidious. [entokey.com]

  HENT exam showed no obvious rashes or lesions; however, the patient had mild hyperesthesia over his right forehead. He had normal ear canals, tympanic membranes, nares, and oropharynx. The patient had no cervical or auricular lymphadenopathy. [ncbi.nlm.nih.gov]

  General pathology Following reactivation, patient may experience symptoms of the prodromal phase including mild fever, nausea, malaise, skin hyperesthesia, tingling and progressive pain. [eyewiki.org]

  It is the most frequent complication, observed in 9-45% of all cases. [4] Most people report a deep burning or aching pain, paresthesia, dysesthesia, hyperesthesia, or electric shock–like pains. [emedicine.com]

• Mydriasis

  The presentation of complete paralytic mydriasis as the sole cranial nerve complication following herpes zoster ophthalmicus infection is a rare finding. [ncbi.nlm.nih.gov]

  FIG. 1: Eyelid ptosis, pupillary mydriasis, and complete ophthalmoplegia of the left eye are present. [journals.lww.com]

  The literature contains one report of bilateral, simultaneous angle closure presumed to be caused by heightened sympathetic tone leading to mydriasis and angle closure.9 TREATMENT Systemic antiviral agents reduce the complications of ocular disease and [glaucomatoday.com]

  Isolated, complete paralytic mydriasis secondary to herpes zoster ophthalmicus. Pract Neurol. 2013;13(3):183-4.). [scielo.br]

The diagnosis of HZO is determined through a detailed history and complete eye exam. The characteristic finding includes a unilateral dermatomal rash on the forehead and/or eyelid. If the patient presents after the rash has healed but has the suggestive history and signs such as hypopigmented scars, suspicion should be high for HZO.

A thorough evaluation warrants an ophthalmology consultation. The ophthalmologic exam consists of numerous components such as external inspection of the eye, testing of extraocular movement and pupillary reflex, and assessing visual fields and acuity. Very importantly, a slit lamp exam, fundoscopy, and corneal exam with and without staining are all performed. Measurement of intraocular pressure is also obtained. These key components will determine associated eye pathology and complications.

Since diagnosis is usually achieved through a history and eye exam, diagnostic testing is rarely performed unless the presentation is atypical. Serologic testing, viral culture, PCR, and immunofluorescence assay are options. Tzanck smear or Wright stain can be utilized but they identify presence of herpes virus in general.

• Human Herpesvirus 3

  Shingles and Shingles Vaccination Synonyms: herpes zoster and varicella zoster Shingles is caused by the human herpesvirus-3 (HHV-3). Primary infection usually occurs in childhood, producing... [evidence.nhs.uk]

  Genus: Varicellovirus Species: Human alphaherpesvirus 3 Synonyms Varicella-zoster virus,[1] VZV Human herpesvirus 3, HHV-3, HHV3, Human alphaherpesvirus 3[2] Varicella-zoster virus (VZV), also known as human herpesvirus 3 (HHV-3, HHV3) or Human alphaherpesvirus [en.wikipedia.org]

  Aetiology Varicella zoster virus (VZV), also known as human herpesvirus-3 (HHV- 3) previous systemic infection (varicella, i.e. chickenpox) virus lies dormant (sometimes for decades) in dorsal root and cranial nerve sensory ganglia reactivation leads [college-optometrists.org]

  Herpes zoster is a common infection caused by the human herpesvirus 3, the same virus that causes varicella (i.e., chickenpox). It is a member of the same family (Herpesviridae) as herpes simplex virus, Epstein-Barr virus, and cytomegalovirus. [aafp.org]

HZO is commonly seen in the emergency department. The components of urgent management include wound care, pain control, antiviral therapy, and management of complications. Certain cases may warrant antibiotic therapy as well. Outpatient treatment is optimal for stable patients without significant eye involvement. Ill patients require inpatient intravenous antivirals and other indicated therapies depending on the presentation.

In early disease, there are three antiviral options 1) acyclovir 800mg orally five times daily for seven days 2) famciclovir 500mg orally three times a day for seven days, or 3) valacyclovir 1g orally three times a day for seven days. If taken early, these antivirals are associated with a profound reduction in adverse outcomes. Additionally, acyclovir has been observed to reduce the occurrence of postherpetic neuralgia if taken within the first three days of initial symptoms [8] [9] [10]. Valacyclovir has demonstrated effectiveness in prevention of conjunctivitis, keratitis and pain [11]. While all options are equally effective, famciclovir and valacyclovir offer less frequent dosing which is more convenient for patient compliance.

Corticosteroids are used in ocular complications. Topical prednisolone is necessary for treatment of uveitis or keratitis. Additionally, corticosteroids may provide pain relief and shorten the length interval of skin healing. However, the use of oral corticosteroids for prevention of postherpetic neuralgia in the elderly is debatable. Pain control is achieved with opioid medications and/or nonsteroidal anti-inflammatory drugs (NSAIDs).

The prognosis of HZO depends on the severity of the disease. Complications may cause visual impairment or blindness, whether short-term or permanent. Corneal damage can result in a significant visual loss. Other long-term manifestations include ocular inflammation and devastating pain. Also, relapses are known to occur even a decade after initial onset.

It is thought that all patients with a nasociliary nerve (sub-branch of the ophthalmic nerve) infection will exhibit pathology in the eye [4]. Since the nasociliary nerve innervates the globe of the eye, the effects of its involvement are more severe. Furthermore, if the tip of the nose is affected, this is indicative of eye manifestations. This is called Hutchinson’s sign. Immunocompromised patients frequently become very ill and exhibit marked visual problems [5].

Herpes zoster ophthalmicus is caused by the varicella zoster virus, also known as herpes virus 3, which is responsible for chickenpox. This virus is a member of the herpes viridae family which also includes herpes simplex virus, Epstein-Barr virus and cytomegalovirus.

Herpes zoster is frequently diagnosed in the emergency room setting. It results from the reactivation of latent virus in the ophthalmic branch of the trigeminal nerve. Specifically this reactivated virus causes inflammation of the sensory nerves that innervate the eye [1].

HZO accounts for 10% to 25% of herpes zoster infections [2]. Almost 50% of HZO patients develop complications and the risk of serious sequelae is not related to gender, age or severity of the rash. Note that the risk of developing HZO is greater in immunocompromised patients such as individuals with HIV [3].

To understand the pathogenesis of HZO, it is important to describe the infection that precedes it. The primary varicella zoster virus (VZV) infection causes chickenpox. After this infection resolves, the virus resides in the dorsal root ganglia and remains dormant for many years. Reactivation of this latent virus in the ophthalmic branch of the trigeminal nerve causes the secondary infection, HZO. Other branches of the fifth cranial nerve may be involved. 

The live varicella zoster virus vaccine (Varivax), available since 1995, is as high as 99% effective in the prevention of infection. A higher potency vaccine (Zostavax) was introduced in 2005. A three-year follow-up study of Zostavax observed a 51% reduction in the incidence of herpes zoster [12]. Herpes zoster and associated complications are common in the elderly, which is attributed to diminished cell-mediated immunity. Therefore, prevention of herpes zoster in this population is crucial. Furthermore, older individuals do well with Zostavax [13].

Zoster vaccination in older individuals is cost effective and beneficial in the prevention of herpes zoster and limitation of its severity [14] [15]. Additionally, post exposure prophylaxis with VZIG is warranted in special populations. Nontherapeutic preventative measures should always be practiced. For example, affected patients should be under respiratory and contact isolation precautions until the lesions fully crust.

Herpes zoster ophthalmicus (HZO) occurs when the latent varicella zoster virus is reactivated in the ophthalmic nerve (V1), which is a branch of the trigeminal nerve (cranial nerve 5). The dosorder is a common emergency room diagnosis, and can account for up to 25% of all herpes zoster infections.

The disease, which occurs in three phases, is most notable for the acute dermatomal rash on the forehead. This rash is associated with painful inflammation of ocular tissues and progresses in a characteristic pattern. Following the acute phase, late sequelae can result in significant eye disease.

Diagnosis is established through a detailed history and physical exam. The presence of a rash in a dermatomal distribution on forehead or eyes or a reported history of this hallmark rash will confirm HZO. A very thorough and prompt ophthalmologic exam consisting of external and internal testing is paramount. Furthermore, evaluation of the eye structures is crucial in determining the presence of any damage. 

Treatment includes antiviral therapy, pain control, and management of any present complications. If treatment with acyclovir, valacyclovir, or famciclovir is initiated within 72 hours of initial symptoms, there is a significant reduction in eye involvement. Varicella zoster vaccines are available. They are very effective and recommended for all adults 60 years old or above. 

Herpes zoster ophthalmicus (HZO) occurs when a previous varicella zoster infection becomes active again. To understand better, it is important to explain the background. When a person has chickenpox, the virus responsible for it can remain in the body and go to sleep. Many years or even decades later, this virus can wake up and start a new infection. In HZO, the new infection occurs in of one the nerves that control the eye. Therefore, the region of the eye develops a painful red rash that follows a certain a pattern. A few days later, the rash blisters and crusts over. Eventually, the blisters become scans and heal over time.

Most people will have swelling and crusting of eyelids. Also, individuals with this disease can develop eye infections such as conjunctivitis as well as damage to important structures in the eye such as the cornea. This can result in visual impairment. Since there serious complications can occur, it is crucial to seek urgent care if one experiences these symptoms. In fact, treatment within 72 hours of the first symptoms can produce better results.

How is the diagnosis made?

The doctor will ask relevant questions and then perform an exam. Usually, an ophthalmologist (special eye doctor) will inspect the eye and perform key tests to check for damage to the function and structures of the eye. S/he uses instruments that shine light into the eye, and also a microscope device for close evaluation. The ophthalmologist will then determine if there are any complications.

How is it treated?

If the disease is mild and there are no eye complications, the doctor will prescribe antiviral and pain medications with close follow-up. Acyclovir, valacyclovir, and famciclovir are the options for antivirals. If taken within the first 72 hours, they can prevent eye involvement. If the patient is ill or has significant eye damage, then hospital admission and aggressive therapy are needed.

Can this be prevented?

There are vaccines available that can prevent herpes zoster infections. They are recommended for people who are 60 years old or more. 

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