HERPES SIMPLEX Herpes simplex infection of the eye: Bhupesh Bagga Consultant an introduction Ophthalmologist : Cornea Institute, Herpes simplex virus has affected two-thirds of the global population at one time L V Prasad Eye Institute, or another. It can affect the eyes when the patient is first infected, or years later Hyderabad, India. when the latent virus is reactivated. ccording to the World Health Organization to a ‘trigger’ such as fever or stress. (WHO), more than 3.7 billion people under Clinically, ocular infection can be subdivided into 50 years – 67% of the global population – Anahita Kate A keratitis, uveitis and retinitis, each of which will be Consultant have been infected with herpes simplex virus at discussed in this article. Ophthalmologist: some point in their life.1 Herpes simplex infection Cornea Institute, can be particularly severe in patients who are Herpes simplex keratitis L V Prasad Eye immunodeficient, e.g., those with acquired immune This can manifest as3: Institute, deficiency syndrome (AIDS). Hyderabad, India. • Infectious epithelial keratitis Herpes simplex virus is categorised into two distinct • Neurotrophic keratopathy types: HSV-1 and HSV-2. • Stromal keratitis • HSV-1 is transmitted via direct contact, usually via • Endotheliitis saliva, and commonly presents as cold sores or Joveeta Joseph Microbiologist : fever blisters. It is also a cause of eye infection and 1. Infectious epithelial keratitis 2 Jhaveri Microbiology significant visual impairment. Clinical features. The earliest presentation is Centre, L V Prasad • HSV-2 is transmitted via sexual contact or from corneal vesicles which later coalesce to form Eye Institute, mother to child during birth (neonatal herpes a dendritic ulcer. The dendritic ulcer (Figure 2) Hyderabad, India. simplex infection). It causes genital herpes presents as a branching linear lesion with terminal infections and, occasionally, ocular neonatal bulbs. The base of the ulcer stains with fluorescein infection. while the margins (virus-infected epithelial cells) stain Herpes simplex virus is usually acquired in childhood positively with Rose Bengal stain. When these ulcers enlarge, they appear geographical (Figure 3) with Vivek Pravin or adolescence. After the initial infection, the virus can Dave enter nerve cells in the dorsal ganglia and lie dormant, well-defined, scalloped margins. Consultant or latent. Ophthalmologist : Diagnosis. This is based on typical clinical signs. Smt. Kanuri Primary ocular herpes infection is often Occasionally, it may be necessary to confirm the Santhamma Centre asymptomatic. The virus can present with cold sores diagnosis with a sample taken from a corneal scraping for Vitreo Retinal which is sent for virological examination, cell culture or Diseases, L V Prasad or fever blisters (vesicular dermatitis – see Figure 1), 4 Eye Institute, follicular blepharo-conjunctivitis, superficial punctate polymerase chain reaction (PCR). Hyderabad, India. keratitis (SPKs) and/or dendritic ulcer. Treatment is controversial as it is often self-limiting, but topical Treatment. The usual treatment recommended is and systemic antivirals have been used. Aciclovir eye topical aciclovir eye ointment 3% five times/day until ointment 3% five times/day or ganciclovir 0.15%, the ulcer has healed. Trifluridine is an alternative 5-times daily for 7 days, and then three times daily for that is used in the USA. Topical ganciclovir 0.15% five a further 7 days is recommended for dendritic ulcers. times/day is an alternative treatment. If there are many recurrences, consider prescribing oral aciclovir Recurrent ocular herpes infection is due to 200 to 400 mg twice/day as prophylaxis. This drug activation of latent herpes virus in the nerve cells (for is considered safe for long-term use with 6-monthly example, the trigeminal ganglion), usually in response evaluation of renal function tests. Figures 1 to 9 show different clinical presentation of ocular HSV infection. Figure 1 Blepharo-conjunctivitis Figure 2 Dendritic ulcer Figure 3 Geographical ulcer LVPEI LVPEI LVPEI 68 COMMUNITY EYE HEALTH JOURNAL | VOLUME 33 | NUMBER 108 | 220 Figure 4 Immune stromal keratitis Figure 5 Necrotising stromal keratitis Figure 6 Disciform endothelitis LVPEI LVPEI LVPEI 2. Neurotrophic keratopathy The diagnosis of necrotising stromal keratitis can also Clinical features. There is impaired corneal be made clinically. For confirmation, the virus can be sensation with a superficial punctate keratitis detected in a corneal scrape using cell culture, indirect that can form an epithelial defect with a smooth immunofluorescence (IFA) or PCR. It is important to margin (in contrast to the scalloped margins of a also exclude secondary bacterial infection. geographical ulcer). A grey-white stromal infiltrate (neurotrophic ulcer) with well-defined, heaped-up Treatment. This depends on the type of inflammation. epithelial margins may develop; this can lead to Immune stromal keratitis is managed with progressive stromal thinning, corneal perforation or topical low-dose corticosteroids 4–6 times/day with secondary infection. gradual tapering for 4–6 weeks, along with either topical aciclovir ointment 5 times/day or topical Diagnosis. Microbiological evaluation with bacterial trifluridine for 2–3 weeks. For recurrent cases, provide culture is recommended to rule out secondary prophylactic cover by giving oral aciclovir 200–400 mg infection. 2 times/day. Treatment. Intense lubrication and prophylactic Necrotising stromal keratitis is treated using antibiotics are recommended. The antibiotics should 400–800 mg oral aciclovir 5 times/day. After complete be kept to a minimum to reduce toxicity to the healing of the epithelial defect, topical corticosteroids epithelium. Antivirals are not indicated. Options for may be added to reduce inflammation, but only with non-resolving cases include bandage contact lens or regular slit lamp examination to look for any recurrence amniotic membrane grafting with tarsorrhaphy if the of infection or corneal thinning, which could lead to expertise and resources are available. corneal perforation. 3. Stromal keratitis 4. Endotheliitis There are two main types of inflammation of the Endotheliitis is presumed to be immunogenically corneal stroma due to herpes simplex virus. mediated, but the presence of live HSV has been postulated in some cases. • Immune stromal keratitis presents with corneal stromal oedema (Figure 4) and folds in Descemet’s Clinical features. Endotheliitis presents with stromal membrane. This is associated with fine keratic oedema, similar to immune stromal keratitis (Figure 6) precipitates (KPs), limbitis and (often) raised with keratic precipitates (KPs) limited to the area of intraocular pressure (IOP); there is no epithelial corneal edema. The endotheliitis can be linear (starting defect. from the corneo-scleral junction and spreading Necrotising stromal keratitis is due to active • centrally), disciform (usually in the centre of the viral infection within the cornea. It presents cornea), or diffuse. with an epithelial defect (Figure 5) and dense stromal infiltration. If the infection is close to the Diagnosis. The diagnosis is made clinically. limbus, then the marginal keratitis shows stromal infiltration and associated vascularisation. Treatment. Low dose topical corticosteroids are Diagnosis. The diagnosis of immune stromal keratitis recommended with prophylactic topical or oral aciclovir is made clinically, and no investigations are required. for 2 weeks. Continues overleaf ➤ COMMUNITY EYE HEALTH JOURNAL | VOLUME 33 | NUMBER 108 | 2020 69 HERPES SIMPLEX Continued Figure 9 Acute retinal necrosis due to herpes simplex virus: multiple peripheral Figure 7 Large pigmented keratic Figure 8 Patchy iris atrophy seen in chronic retinitis patches, sclerosed arteries, arteriolar precipitates herpetic kerato-uveitis sheathing in periphery LVPEI LVPEI LVPEI Herpes simplex uveitis Clinical features. There are large, white retinal Herpes simplex-associated anterior uveitis accounts infiltrates, sheathing of the retinal vessels Figure( 9) for 5–10% of all uveitis cases.5 It is more common and inflammatory cells in the vitreous (vitritis). On in older age groups, almost always unilateral and is healing, there are large areas of scarred (atrophic) associated with raised intraocular pressure (IOP). retina. Pathogenesis may be due to direct infection by the virus or an immune response. Diagnosis. Vitreous or aqueous tap for PCR to confirm presence of viral DNA. Clinical features. There are five clinical features which, seen together (not in isolation), characterise HSV Treatment. On diagnosis, promptly start the anterior uveitis6: following treatment regimen in order to limit disease progression: antiviral treatment with intravenous • Recurrent episodes of unilateral anterior uveitis aciclovir (5–10 mg/kg every 8 hours) for 5–10 days; Past history of herpes simplex infection • followed by oral aciclovir (800 mg, 5 times/day) for Raised IOP • 4–6 days. Retinal detachment following acute retinal Diffuse KPs (Figure 7) • necrosis (ARN) can be managed with a pars plana Patchy or sectoral iris atrophy (Figure 8) • vitrectomy and silicone oil tamponade.7,8 Diagnosis. Diagnosis can be confirmed by References an anterior chamber (AC) tap and PCR for 1 Looker KJ, Magaret AS, May MT, Turner KME, Vickerman P, et al. Global herpes simplex virus, or the Goldmann–Witmer and regional estimates of prevalent and incident herpes simplex virus coefficient (GWC) test . The GWC