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Herpes Zoster Ophthalmicus (HZO) is caused by reactivation of the latent Varicella zoster virus (VZV) from the trigeminal ganglia with ocular involvement. VZV is a highly contagious infection that produces varicella (chickenpox) and herpes zoster (shingles). Herpes zoster derives its name from Greek word herpein meaning ‘to spread’ or ‘to creep’, and zoster meaning ‘girdle’ or ‘zone’.  Increasing age represents a significant risk factor for herpes zoster infection. Altered cell mediated immunity is another important risk factor. Patients with neoplasia, on immunosuppressive drugs, organ transplant recipients, and human immunodeficiency virus (HIV) infection are particularly at risk for herpes zoster infection.

Hutchinson (1865) was the first person to describe the signs and symptoms of herpes zoster ophthalmicus.

Out of the three divisions of trigeminal nerve (Ophthalmic, maxillary, and mandibular), the ophthalmic division is most commonly involved. Ophthalmic division divides into three branches known as nasociliary, frontal, and lacrimal branches. Frontal branch is most commonly affected and the lacrimal is least commonly involved. Nasociliary branch supplies the skin of both eyelids, conjunctiva, cornea, sclera, uveal tissue, anterior and posterior ethmoidal sinuses, and tip of the nose. Because of extensive innervation by nasociliary branch, its involvement by disease process has high probability of ocular complications. Vesicles affecting tip of the nose is known as Hutchinson sign and is an indicator of potential involvement of eye.

Acute herpes zoster infection produces one to four days of prodromal symptoms such as fever, headache, malaise, pain, burning erythema, and itching in the affected dermatome. Release of virus from nerve endings results in macular rash, which becomes papular and then vesicular. New vesicles continue to form for about four days, and this period is extended to weeks in immunosuppressed individuals. Vesicles may become pustular or may bleed. Haemorrhagic necrosis of dermal tissues may occur with propensity of pigmentation and scarring. Occasionally, herpes zoster infection may occur without cutaneous eruptions (zoster sine herpetica). Visceral dissemination is a more severe complication and most commonly it may affect lungs and gastrointestinal system. The acute phase subsides after two to three weeks when rash crusts and dissipates. The pain may persist even after dissipation of crusts and is known as post-herpetic neuralgia.

 

References

Yanoff Myron, Duker Jay S. Ophthalmology Third Edition. Mosby, an imprint of Elsevier Inc. 2009. P 222- 226.

Mannis Mark J, Holland Edward J. Cornea- Fundamentals, Diagnosis and Management Fourth Edition. Elsevier Inc. 2017. P 943- 955.

Yanoff Myron, Sassani Joseph W. Ocular Pathology Seventh Edition. Saunders, an imprint of Elsevier Inc. 2015. P 72- 73.

Bowling Brad. Kanski’s Clinical Ophthalmology- A Systematic Approach Eighth Edition. Elsevier Limited 2016. P 32-33.

Kanski Jack J, Bowling Brad. Clinical Ophthalmology- A Systematic Approach Seventh Edition. Elsevier Saunders, an imprint of Elsevier Limited 2011.

Nussenblatt Robert B, Whitcup Scott M. Uveitis- Fundamentals and Clinical Practice Fourth Edition. Mosby Elsevier, an imprint of Elsevier Inc. 2010. P 186-187.

Kanski Jack J, Bowling Brad. Ophthalmology in focus. Elsevier Churchill Livingstone, an imprint of Elsevier Limited 2005. P 32.

Lee W R. Ophthalmic Histopathology. Springer-Verlag London 1993. P 136- 138.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2672268/

https://www.bmj.com/content/364/bmj.k5234

https://emedicine.medscape.com/article/1132465-treatment

http://www.ijo.in/article.asp?issn=0301-4738;year=1996;volume=44;issue=1;spage=40;epage=42;aulast=Nath

Patient may present in acute phase with

Prodromal Symptoms

  • Fever
  • Malaise,
  • Headache
  • Pain
  • Burning

 

Cutaneous symptoms

  • Hypesthesia (Absent or reduced sensitivity)
  • Itching
  • Erythema
  • Oedema
  • Macular or papular rash
  • Vesicles (dermatomal distribution)

 

Ocular symptoms

  • Pain
  • Redness
  • Discharge
  • Photophthalmia
  • Diminution of vision

 

Varicella-zoster virus (VZV) causes chickenpox (varicella) as well as shingles (herpes zoster). VZV is morphologically similar to herpes simplex virus (HSV). Following chickenpox, VZV travels in retrograde manner to the dorsal root or cranial nerve sensory ganglion, where it may remain dormant for years. On reactivation, HZO produces shingles in the dermatome supplied by the ophthalmic division of the trigeminal nerve.

Mechanism of eye involvement

  • Direct viral invasion: It may produce epithelial keratitis and conjunctivitis.
  • Secondary inflammation: Occlusive vasculitis may produce episcleritis, scleritis, keratitis, uveitis, or optic neuritis.
  • Reactivation: It produces necrosis and inflammation in the affected sensory nerve ganglion, which may result in corneal anaesthesia/neurotrophic keratitis.

 

Herpes zoster manifests with acute, chronic, or relapsing phases.

Diagnosis depends upon history and clinical features.

Periocular skin and eyelids: Oedema of eyelids is usually the first sign of HZO, which is accompanied by pain, pruritus, and hypaesthesia. Maculopapular rash develops which is followed by vesicular eruptions. The vesicles heal within two to three weeks leaving residual pitting and pigmentation. The lid may show ectropion, entropion, poliosis, madarosis, or trichiasis. Haemorrhagic vesicular eruption may be due to vasculitis and heralds severe scarring and post-herpetic neuralgia. Cicatricial contraction of eyelids may produce exposure keratopathy.

Conjunctiva: HZO may produce papillary or follicular reaction, chronic hyperaemia, or pseudo-membrane. Vesicles may develop in conjunctiva with possible haemorrhage. Severe conjunctival involvement may lead to conjunctival/punctal scarring, punctal occlusion with epiphora, or formation of symblepharon.

Episclera: HZO may cause episcleritis during acute phase or even months later after disappearance of vesicles. It is found typically during early phase and may persist up to or beyond three months.

Sclera: HZO may cause anterior or posterior scleritis. Scleritis is usually diffuse anterior or nodular and may lead to peripheral limbal vasculitis. Chronic scleritis may lead to scleral thinning and even staphyloma formation.

Cornea: Cornea may develop manifestations such as

  • Punctate epithelial keratitis: The lesions are usually peripheral, coarse, multiple, and are raised.
  • Pseudodendrites: These present as multiple stellate dendritic lesions of oedematous raised epithelial cells. These probably represent coalescence of peripheral punctate epithelial keratitis. In contrast to herpes simplex dendrites, pseudodendrites are  superficial, lack central ulceration, have blunt ends, and stain poorly with dyes.
  • Anterior stromal infiltrates: These present as isolated or multiple, hazy, granular infiltrate beneath Bowman’s membrane. These may leave behind nummular scars.
  • Endotheliitis: There may be sudden onset of diffuse or localised Descemet’s folds with subsequent stromal and epithelial oedema. This may be due to direct viral invasion of endothelium.
  • Corneal mucous plaques: These manifests in a quiescent eye or in an eye with minimal keratitis. These present as elevated coarse white branching lesions on surface of oedematous epithelial cells. Unlike true dendrites, these lack terminal branches and have sharp margins.
  • Disciform keratitis: A peripheral disk shaped lesion may develop several weeks after acute HZO infection.
  • Neurotrophic keratopathy: It represents diminution of corneal sensations with loss of corneal integrity with subsequent epithelial breakdown.
  • Interstitial keratitis: This shows as paracentral or peripheral vascular leash with lipid deposits in horizontal corneal meridian with significant corneal scarring.
  • Corneal oedema: VZV may produce temporary or permanent corneal oedema probably by vasculitis, endothelial destruction, or by an immune mechanism.

Sclerokeratitis: Scleritis may be associated with limbal vascular keratitis. It manifests as scleralisation, stromal thinning, or vascularisation.

Uveitis: It may be associated with keratitis and may be keratic precipitates (K P’s) present on posterior surface of cornea.

Secondary Glaucoma: The glaucoma may be produced due to extension of VZV to the trabecular meshwork or ischaemic vasculitis of ciliary body.

Post-herpetic neuralgia: It refers to unremitting pain lasting for months to years after resolution of acute infection.

 

Laboratory investigations

  • Tzanck smear: It is a simple morphologic test, which identifies multinucleated giant cells and acidophilic intranuclear inclusions in scraping taken from cornea or base of a vesicle.
  • Light microscopy and electron microscopy: These confirms infection with herpes virus in skin biopsy.
  • Immunoperoxidase, polymerase chain reaction and enzyme-linked immunosorbent assay: These immunologic tests can detect viral particles.
  • Isolation of VZV: Identification of VZV by culture of fluid from vesicle is a definitive test.

 

Differential diagnosis

It include conditions such as

  • Herpes simplex infection
  • Impetigo

Management includes

Supportive therapy

Supportive therapy to provide symptomatic relief. Therapy includes

  • Maintenance of hydration with adequate fluid intake
  • Antipyretics
  • Proper hygiene to prevent secondary bacterial infections.

 

Medical therapy

I. Systemic

  • Oral acyclovir: It reduces viral shedding, systemic dissemination of virus, and incidence/ ocular complications, particularly if used within seventy-two hours of onset of symptoms. It also shortens duration of pain if taken early.
  • Intravenous acyclovir: It may be used in immunocompromised individuals.
  • Famciclovir: This is a prodrug of penciclovir and has a much higher bioavailability than acyclovir. It is well tolerated and safe with similar efficacy to acyclovir.
  • Valacyclovir: It is ester of acyclovir and has greater bioavailability than acyclovir. It has similar efficacy in the prevention of ocular complications and in the prevention of sequelae of herpes zoster. It significantly accelerate resolution of pain as compared to acyclovir.

 

II. Local ocular therapy

Skin care: It includes

  • Mechanical cleansing of affected skin
  • Cold compresses
  • Local application of antibiotic without steroids

Eye: Local debridement of lesions help when it is supplemented along with systemic therapy.

 

Neurotrophic keratitis/Epithelial defects: These may be treated with

  • Artificial tears (non-preserved)
  • Eye ointment
  • Pressure bandage
  • Therapeutic soft contact lenses.
  • Punctal occlusion
  • Conjunctival flap
  • Autologous conjunctival transplantation
  • Tarsorrhaphy

Use of steroids

  • Topical steroids are used judiciously in the management of Sclerokeratitis, interstitial keratitis, disciform keratitis, anterior stromal infiltrates, HZO glaucoma and keratouveitis.
  • Topical, periocular, or systemic steroids may be used for their anti-inflammatory action in vitreous debris/ haemorrhage, or HZO vitritis.
  • Systemic steroids along with intravenous acyclovir may be beneficial in HZO optic neuritis, chorioretinitis, acute retinal necrosis, retinitis, and progressive outer retinal necrosis.

Post-herpetic neuralgia (PHN): It may be treated with

  • Local capsaicin cream: It is applied locally for providing relief in pain.
  • Famciclovir and valacyclovir: These significantly reduce duration but not incidence of PHN
  • Analgesics.
  • Antidepressants: Antidepressant like amitriptyline when used for ninety days, reduces incidence of pain at six months.
  • Percutaneous electrical nerve stimulation (PENS): A trial has suggested decrease in pain when compared with use of famciclovir.

Occasionally, some patients with severe and intractable pain may require psychiatric consultation, trigeminal rhizotomy, or stellate ganglion block.