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The etiopathogenesis and management strategies in various manifestations of viral keratitis is shown in Table 9.5.

INFECTIOUS EPITHELIAL KERATITIS

The treatment of the infectious epithelial keratitis consists of physical debridement, topical antiviral agents, cycloplegics and tear substitutes.15

Physical debridement of the infected epithelial cells should be done with cotton tipped applicator. Topical antiviral drugs in the form of 3 percent acyclovir ointment 5 times/day or 1 percent trifluridine solution 2 hourly when awake are given for the first week. In cases which are responsive to therapy, after a week of treatment, these drugs are tapered that is, acyclovir is given three times a day and trifluridine is given 5 times per day. These are then continued in these doses for the rest of the treatment which lasts for 21 days. These drugs are discontinued after 3 weeks of therapy even when the ulcer does not heal completely. Generally, infectious epithelial keratitis shows signs of healing by 2 weeks.

Cycloplegics (2% Homatropine hydrobromide or 1% Cyclopentolate hydrochloride) are added when iritis is present. Topical antivirals are very epitheliotoxic and it is imperative to give concomitant preservative free artificial tears (Hydroxypropyl methylcellulose 0.3% eye drops) to keep the epithelium lubricated.

In certain cases, if the dendritic patterns still persist after 2 weeks of therapy, a careful assessment is required if it is a true ulceration or a dendriti form epitheliopathy. The latter is a healing response of epithelium and is there is absence of any ulceration.

Corticosteroid drops are not recommended in the management of infectious epithelial keratitis unless significant stromal involvement coexists. In the event

of coexisting stromal disease topical 3 percent acyclovir eye ointment is applied 5 times a day for 4-5 days to decrease the viral load and then topical corticosteroids (1% prednisolone acetate ophthalmic suspension) is started at a frequency of 2 to 4 hourly depending on the severity of stromal disease.19 _{After a week both the} antiviral and corticosteroid are tapered very gradually over a period of 6 to 8 weeks. Sometimes tapering should be done over a longer period of time as the stromal disease has a tendency to recur immediately after the topical corticosteroids are stopped.

At times infectious epithelial keratitis may not respond to the topical antiviral medications. It is mandatory to re-scrape and send them for cultures as Acanthamoeba may be isolated in 70% of these cases.20 Resistance generally does not occur in cases of viral keratitis; however if it occurs, and the patient is on acyclovir, vidarabine may be tried instead of acyclovir; trifluridine in these cases should not be used instead as trifluridine and acyclovir work by the same mechanism.

NEUROTROPHIC KERATOPATHY

Treatment is aimed at protecting the damaged basement membrane. Therapeutic approaches include stopping topical antiviral agents which may be epitheliotoxic and using preservative free artificial tears and ointment. In case the epithelium becomes boggy gentle debridement should be done. In cases of non-healing ulcers thera- peutic bandage contact lenses may be given along with topical antibiotics to prevent contact lens induced microbial keratitis. Alternatively, a surgical tarsorrhaphy may be done or botulinium toxin injection may be given to cause a temporary lid closure. In severe cases, conjunctival flaps may be undertaken or amniotic membrane transplantation may be done (Figs 9.16A to C).

Table 9.4 Antiviral agents

Antiviral agent Route Strength frequency Mechanism of action

Vidarabine (Ara-A) Topical 3% ointment Five times a day Inhibits viral DNA polymerase Trifluridine Topical 1% solution 2 hourly while awake Inhibits viral thymidylate synthase Acyclovir Topical, Oral 3% ointment Five times a day Activated by viral thymidine kinase

200,400 mg tablets to inhibit DNA polymerase Valacyclovir Oral 1000 mg Three times a day Activated by viral thymidine kinase

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IMMUNOLOGIC DISEASE

A combination of antiviral drug and topical steroids is the recommended line of treatment of immune mediated HSV keratitis such as immune stromal keratitis and necrotizing stromal keratitis.

Immune Stromal Keratitis

Topical steroids are the mainstay for cases of immune stromal keratitis. Topical steroids reduce the severity and of stromal inflammation, decrease the duration of

stromal keratitis and reduce corneal scarring, neovascu- larization and posterior synechiae formation.

Topical corticosteroids (1% Prednisolone acetate ophthalmic suspension, 4 times a day) should be started in mild cases. In more severe cases topical corticosteroids should be instilled every hour. In all the cases administration of topical corticosteroids should be accompanied with instillation of antiviral drugs (1% trifluridine solution or 3% acyclovir ointment).

A mydriatic–cycloplegic drug (2% homatropine hydrobromide or 1% cyclopentolate hydrochloride) added to reduce ciliary spasm.

Table 9.5

Summary of clinical manifestations and management of viral keratitis

Lesion Etiopathogenesis Topical treatment Systemic treatment Remarks

Dendritic keratitis Infection by live herpes 3% topical acyclovir ointment None Heals without significant simplex virus (5 times/day) or 1% trifluridine corneal scarring

solution (2 hourly) Epithelial debridement ±

Amoeboid/ Infection by live 3% topical acyclovir ointment None Heals without significant geographical ulcer herpes simplex virus (5 times/day) or 1% trifluridine corneal scarring

solution (2 hourly) Epithelial debridement ± May add topical antibiotic drops prophylactically

Neurotrophic keratitis Noninfectious, Lubricants, BCL, patching, Collagenase Low dose topical ↓ corneal sensitivity tarsorrhaphy, amniotic inhibitors like corticosteroids and

membrane tetracycline topical antiviral if stromal edema and inflammation present Immune mediated Immune reaction to Topical antivirals and None Very gradual tapering of stromal keratitis herpes virus antigen topical corticosteroids topical therapy

Necrotizing stromal Active viral replication Topical corticosteroids Gradual tapering off keratitis in corneal stroma (1% prednisolone acetate topical therapy

suspension, 4 times a day) with 3% topical acyclovir ointment (5 times/day) or 1% Trifluridine solution (9 times/day) ± mydriatic – cycloplegic drug (2% Homatropine hydrobromide or 1% cyclopentolate hydrochloride)

Endothelitis/ Immune reaction to Topical corticosteroids (1% Gradual tapering off Disciform keratitis viral antigen Prednisolone acetate ophthalmic topical therapy

suspension, 4 times a day) with 3% topical acyclovir ointment (5 times/day) or 1% trifluridine ± mydriatic – cycloplegic drug (2% homatropine hydrobromide or 1% cyclopentolate hydrochloride) solution (2 hourly)

Necrotizing Stromal Keratitis

Topical corticosteroids (1% Prednisolone acetate ophthalmic suspension, 4 times a day) should be started in mild cases. In more severe cases topical corticosteroids should be instilled every hour. In all the cases administration of topical corticosteroids should be accompanied with instillation of antiviral drugs (1% trifluridine solution or 3% acyclovir ointment).

A mydriatic–cycloplegic drug (2% homatropine hydrobromide or 1% cyclopentolate hydrochloride) added to reduce ciliary spasm.

Topical corticosteroids should be tapered very gradually over months (more than 10 weeks) to avoid reactivation and rebound inflammation. In some patients topical corticosteroids cannot be tapered off without reactivation of the disease and in such cases low dose topical corticosteroids (0.01% dexamethasone ophthalmic solution or 0.125% prednisolone acetate ophthalmic suspension, 1 drop every day or every alternate day) should be continued indefinitely.

IRIDOCYCLITIS AND TRABECULITIS

It is mainly an immune reaction to viral antigen and in some cases to intact virus. The Herpetic Eye Disease Study (HEDS) found a trend toward improved response of herpetic iridocyclitis and trabeculitis when oral acyclovir was added to topical trifluridine and corticosteroids.19 _{A combination of oral antivirals and} topical corticosteroids may provide sufficient antiviral coverage to allow for the desired suppression of immune response.

Patients are treated with combination of topical corticosteroids (1% Prednisolone acetate suspension, 4 times a day) and antiviral drugs (1% trifluridine solu- tion or 3% acyclovir ointment) along with cycloplegics

(2% homatropine hydrobromide or 1% cyclopentolate hydrochloride). Beta blocker (0.5% timolol maleate 2 times/day) and carbonic anhydrase inhibitor should be added to the above treatment if there is secondary glaucoma. Oral acyclovir 200 mg 5 times a day may be added in cases of severe uveitis or if live virus is isolated from the anterior chamber.

Recently, the efficacy of topical cyclosporine 0.05 percent (Restasis) in patients with herpes simplex virus non-necrotizing stromal keratitis unresponsive to topical prednisolone has been studied. It was found that herpes simplex virus stromal keratitis can be treated effectively with topical cyclosporine.21