HSV Infections PDF

HSV Opto 1640  ❖ Most common virus in humans ~90% of population HERPES Often asymptomatic ❖ Leading cause of infectious SIMPLEX...

HSV Opto 1640  ❖ Most common virus in humans ~90% of population HERPES Often asymptomatic ❖ Leading cause of infectious SIMPLEX blindness in U.S. The double stranded DNA virus Trachoma #1 globally ❖ Most common manifestations: Orofacial lesions Cold sores HSV-1 “above the belt” ❖ Lips/Mouth ❖ Face ❖ Tongue ❖ Eyes Most common ❖ Can occur anywhere ❖ Lays dormant in trigeminal ganglia Transmission: Direct contact HSV-2 “below the belt” ❖ Genitalia ❖ Confirmed with multinucleated giant cells on a Wright Gram stain ❖ Lays dormant in sacral ganglia Transmission: Sexual or Neonatal (most common) HSV-1 Pathogenesis ❖ Initial infection Travels to nerve ganglia 24-48 hours after initial exposure ❖ Latency Hides in trigeminal ganglion Source of recurrent episodes Can lie latent in corneal stroma Not vulnerable to treatment while latent HSV-1 Pathogenesis ❖ Potential reactivation causes: Immunodeficiency Stress Psychological Physical Hormonal changes Sun exposure ❖ Reactivation typically occurs at the original site HSV-1 Pathogenesis ❖ Frequency of reactivation Majority: never 1 reactivation = 40% chance of additional reactivation Short duration between episodes = increased chance of recurrence Severe 1st episode = increased chance of recurrence  HSV Pathogenesis ❖ Two categories: Primary Typically children 94% subclinical Kaposi’s Usually presents as: Blepharoconjunctivitis Recurrent Usually presents as: Keratitis Can also cause: Retinitis Uveitis Optic neuritis Primary HSV: Blepharoconjunctivitis Signs: Periocular vesicles ○ Usually at lateral canthus ○ Full of replicating virus ○ Crust and scab, but do not scar Follicular conjunctivitis Ipsilateral preauricular lymphadenopathy Ulcerative blepharitis possible ○ Ulcers at margin ○ No scarring Primary HSV: Blepharoconjunctivitis Symptoms: Pain, tenderness, tingling Itching Red eyelid Lid swelling Red eye Tearing Photophobia Primary HSV: Blepharoconjunctivitis Treatment: Can resolve on its own Hygiene and lubrication Supportive ○ Warm & cool compress Dry agents ○ Calamine lotion, camphor oil, 70% alcohol Antibiotic ung if secondary infection Monitor if corneal involvement Primary HSV: Blepharoconjunctivitis Consider: Systemic antivirals ○ Acyclovir 400mg po 5x/day x 1 week ○ Valtrex 1g po qd x 1 week Topical antivirals ○ Viroptic 9x a day x 1-2 weeks ○ Zirgan gel 5x a day x 1-2 weeks HSV Recurrent Infections 1. Epithelial keratitis a. Dendritic keratitis (classic) i. Geographic keratitis b. Corneal vesicles c. Marginal keratitis 2. Stromal keratitis a. Without ulceration i. Immune stromal keratitis 1. Interstitial keratitis b. With ulceration i. Necrotizing keratitis 3. Endothelium a. Disciform keratitis 4. Neurotrophic Keratopathy Photo: HSV Stromal Keratitis HSV Recurrent Epithelial: Dendritic Keratitis Signs: Conjunctival injection Mild serous discharge Swollen epithelial cells Linear branching dendritic ulcer ○ Terminal bulbs ○ Dichotomous branching Decreased corneal sensation Mild subepithelial haze Possible elevated IOP HSV Dendritic Keratitis Symptoms: Red, irritated eye FBS Photophobia Tearing Blurry vision Photo: Dendritic corneal ulcer due to recurrent keratitis by HSV HSV Dendritic Keratitis Treatment: Can resolve on own ○ But, risk of scarring and neovascularization Cycloplegic for comfort Artificial tears NO STEROIDS ○ Can lead to increased severity Geographic ulcer Photo: Geographic Ulcer HSV Dendritic Keratitis Topical Treatment: ○ Zirgan (Ganciclovir) gel 5x/day Less toxic, better dosing Taper when cornea re- epithelialized $$$ no generic ○ Viroptic (Trifluridine) 9x/day VERY TOXIC TO CORNEA Taper when cornea re- epithelialized Lower cost generic available HSV Dendritic Keratitis Debridement ○ Decreases viral load ○ Protects adjacent healthy epithelium ○ May decrease scarring ○ Faster resolution ○ Eliminates antigen response for stromal inflammation ○ Prior to drug initation, or if poor response to meds HSV Dendritic Keratitis Oral Treatment ○ Acyclovir 400 mg po 5x/day x 1-2 weeks ○ Valacyclovir 500 mg TID x 1- 2 weeks HSV Recurrent Epithelial: Marginal Keratitis Lesion close to limbus Appear similar to staphylococcal ulcers ○ More stromal inflammation ○ More resistant to treatment Can become a trophic ulcer ○ Ulcer that does not contain live virus ○ Can be caused by medication toxicity HSV Recurrent Epithelial: Corneal Vesicles Early sign of active viral replication Small, raised, clear lesions Epithelium Contain active virus  HSV Recurrent Stromal: Immune mediated inflammation ❖ Focal, multifocal, or diffuse stromal opacities ❖ Considered interstitial keratitis if edema is accompanied by neovascularization Can result in significant scarring Ghost vessels when quiescent ❖ Inflammatory response to the viral replication within the stroma ❖ Treatment: Oxervate  HSV Recurrent Stromal: Immune mediated inflammation Signs: ❖ Multiple or diffuse white corneal stromal infiltrates With or without epithelial defects ❖ Stromal inflammation ❖ Stromal thinning ❖ Stromal neovascularization ❖ Uveitis and hypopyon possible HSV Recurrent Endothelial: Disciform Keratitis ❖ Result of endotheliitis ❖ Inflammatory response to viral antigen resulting in disc-shaped area of corneal edema ❖ Unilateral (usually) Photo: Disciform keratitis with stromal thickening and keratic precipitates HSV Recurrent Endothelial: Disciform Keratitis Signs: ❖ Central round zone of stromal edema ❖ Descemet’s folds ❖ KPs underlying edema ❖ Elevated IOP ❖ Decreased corneal sensitivity HSV Recurrent Endothelial: Disciform Keratitis Treatment: ❖ Topical steroid Pred forte QID Looong taper Drop down to QD then to every other day May be a year long taper ❖ Oral antiviral prophylaxis Topical (trifluridine, ganciclovir) Oral (Acyclovir)  HSV Recurrent Infections: Keratouveitis ❖ Classic presentation is marked corneal edema with anterior chamber reaction and “mutton- fat” KPs on endo ❖ Hypopyon ❖ Rubeosis ❖ Elevated IOP ❖ Live virus released into aqueous Photo: HSV keratouveitis with hypopyon HSV Recurrent Infections: Keratouveitis Treatment: Cycloplegic Topical steroid Pred forte QID Glaucoma tx if IOP high Timolol 0.5% BID NO prostaglandins Topical or oral antiviral Viroptic 9x/day Acyclovir 400 mg po 5x/day Summary ❖ HSV epithelial keratitis diagnosed based on clinical findings Lab testing seldom ❖ Long term complications Resolution of HSK does not prevent future complications ❖ Risk of stromal disease increases with every recurrence of HSV epithelial keratitis ❖ Scarring is common with HSK ❖ Corneal hypesthesia is a hallmark sign of previous HSK Loss of ganglion cells with recurrent infections ❖ Treatment of epithelial keratitis differs from stromal keratitis Dendrites: Simplex vs. Zoster Simplex: Large dendrites with central ulceration and terminal bulbs Zoster: small, medusa-like dendrites WITHOUT central ulceration or terminal bulbs  Herpetic Eye Disease Study (HEDS) I & II HEDS I -To evaluate the efficacy of topical corticosteroids in treating herpes simplex stromal keratitis in conjunction with topical trifluridine. -To evaluate the efficacy of oral acyclovir in treating herpes simplex stromal keratitis in patients receiving concomitant topical corticosteroids and trifluridine. -To evaluate the efficacy of oral acyclovir in treating herpes simplex iridocyclitis in conjunction with treatment with topical corticosteroids and trifluridine. HEDS II -Determine whether early treatment (with oral acyclovir) of herpes simplex virus (HSV) ulcerations of the corneal epithelium prevents progression to the blinding complications of stromal keratitis and iridocyclitis. -To determine the efficacy of low-dose oral acyclovir in preventing recurrent HSV eye infection in patients with previous episodes of herpetic eye disease. -To determine the role of external factors (such as ultraviolet light or corneal trauma) and behavioral factors (such as life stress) on the induction of ocular recurrences of HSV eye infections and disease HEDS-1 No benefit to oral acyclovir in active stromal keratitis if patients were already on topical steroids and topical antivirals Topical steroids useful in treating stromal keratitis Decreases risk of persistent/progressive stromal disease by 68% HEDS-2 Oral acyclovir 400 mg po bid Reduces recurrence by 41% Reduced stromal keratitis by 50% No benefit in preventing epithelial disease converting to stromal disease HEDS-2 Chronic suppressive therapy (oral acyclovir) $8,632.00 Treatment at time of episode $300.00 Conclusion: Prophylactic therapy is $$$ May want to only consider for high risk or stromal disease  HEDS-2 ❖ Those who were not treated prophylactically: 9.4x more likely to have epithelial keratitis 8.4x more likely to have stromal keratitis 34.5x more likely to have blepharitis or conjunctivitis Prophylactic treatment is important, but the debate continues for when to initiate... HEDS Conclusions Summary ❖ For stromal: topical prednisolone has faster resolution ❖ For stromal: no benefit to oral acyclovir when already treating with topical steroid and antiviral ❖ For keratitis: no benefit to oral acyclovir when already treating with topical antiviral ❖ For iridocyclitis: Potential benefit to adding oral acyclovir when patient is treated with topical steroid and an antiviral ❖ No association found between stress factors and HSV recurrences ❖ Oral acyclovir reduced recurrence rate; but effect did not persist once medication was stopped ❖ Lots of limitations… Inadequate recruitment High dropout rate Oral acyclovir only used for 3 weeks Steroid regimen standardized, not personalized Case #1 55-year-old AA male presents with hazy vision OS x 3 weeks. Evaluated at urgent care 2 weeks ago; diagnosed with acute anterior uveitis OS and rx’ed 1% pred acetate q2h and 1% atropine BID. BCVA 20/20 OD, 20/40 OS Pupil: pharmacologically fixed, (-)APD SLE: dendritic ulcer with central NaFl staining and mild underlying anterior stromal edema without infiltration. Anterior chamber deep and quiet. Corneal sensitivity: absent OS PA: not palpable DFE and IOP: normal and unremarkable Case #1 Case #1 What’s your diagnosis? Herpes Simplex Epithelial Keratitis What’s your treatment? Oral acyclovir 400 mg 5x a day for 10 days RAPID prednisolone taper, QID for 2 days then decreasing by 1 drop every 2 days Case #1 RTC 3 times over 2 weeks. Epi defect closed; vision improved to 20/25. 1 week after oral acyclovir was completed, patient reported hazy vision OS. VA still 20/25. SLE focal disciform stromal edema with bullae and underlying KPs. No stromal neovascularization or infiltrate noted. Case #1 What’s your diagnosis? Herpes simplex endotheliitis What’s your treatment? Restart topical 1% prednisolone acetate QID OS and oral acyclovir 400 mg 5x a day for 14 days, then BID after that for prophylactic dosing Case #2 88-year-old male presents with mild redness and irritation OS. OHx of DES treated with cyclosporine 0.09% BID OU. VA sc 20/30 OD, 20/25 OS SLE: OS: paracentral dendritic lesion with 1+ conjunctival injection and endothelial inflammatory cells. Rare cells and mild flare in AC. IOP: 11, 12 mmHg OD, OS Corneal sensitivity decreased OS MHx dendritic keratitis with prolonged course of diffuse epitheliopathy and corneal non-healing Case #2 Case #2 What’s your diagnosis? Herpes simplex dendritic keratitis What’s your treatment? Rx Valtrex 1000 mg BID and Zirgan 5x a day OS. Continue cyclosporine gtts. Case #2 Follow-up exam 1 week later VA dropped to CF @ 2ft OS Dendrite resolved Dense, diffuse corneal epitheliopathy and endothelialitis Discontinued topical ganciclovir. Continue oral Valacyclovir. Rx’ed tobradex gtts QID OS. Placed amniotic membrane OS. 8 weeks later. All resolved. Rx’ed gabapentin for post-herpetic neuralgia.