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Grand Rounds Conference Reema Syed, MBBS University of Louisville Department of Ophthalmology and Visual Sciences August 7, 2015 Subjective CC: Pain and redness, left eye x 2 weeks HPI: 23 year old female with progressively worsening symptoms for 2 weeks. She was recently treated at an urgent care center with “antibiotic eye drops” History POH, PMH: unremarkable Eye Meds: “antibiotic drop” OS QID Systemic Meds: None Allergies: NKDA Objective BCVA: Pupils: IOP: EOM: CVF: OD OS 20/20 20/200 5 to 3 mm OU, no rAPD 13 16 Full Full Full Full Objective SLE: Unremarkable OD OS External/Lids Normal Conjunctiva/Sclera Cornea 2+ injection small epithelial defect; stromal edema; KPs; neovascularization 0.5+cell, trace flare Normal Clear Poorly visualized Anterior Chamber Iris Lens Posterior segment Anterior segment OS Corneal stromal edema in a circular form, infero-central epithelial defect 2x2 mm, inferior neovascularization from limbus to edge of ulcer Anterior segment OS KPs underlying zone of edema Impression 23 year old female with herpetic disciform keratitis OS Differential diagnosis Bacterial keratitis Neurotrophic ulcer Plan Acyclovir 400 mg PO 5 times daily Vigamox QID OS Cyclopentolate 1% BID OS Pred Forte 1% OS QID Follow-up Patient lost to follow-up Stopped using all medicines in few weeks when she felt better Herpes Keratitis Herpes viruses: HSV 1 HSV 2 VZV CMV EBV HHV 8 HHV 6 HHV 7 Pathophysiology Primary infection: Skin and mucosal surfaces innervated by CN V Frequently, non-specific URI Vesicular blepharitis, follicular conjunctivitis, rarely epithelial keratitis Latent infection: Infected skin and mucosal lesions sensory nerve axons sensory nerve ganglia Pathophysiology Recurrent disease: HSV-1 Occurrence May reactivate frequently Incidence drops with age Typically unilateral, usually same site as 1o infection but can occur along any of the 3 branches of CN V Causes of reactivation Role of environmental and physiological factors controversial Bilateral recurrent ocular disease in atopic dermatitis Pain upon reactivation Mild-moderate Sensory loss with repeated recurrence Kinchington PR et al. Herpes simplex virus and varicella zoster virus, the house guests who never leave. Herpesviridae. 2012 Jun 12;3(1):5 HSV Epithelial Keratitis Punctate keratitis Dendritic ulcer Geographic ulcer HSV Epithelial Keratitis Management: Self-limited disease, treatment shortens clinical course, reduces herpetic neuropathy and sub-epithelial scarring Topical Trifluridine 1% x8/day – epithelial toxicity with extended use Oral Acyclovir 400 mg x5/day or Valacyclovir 500 mg TID – same efficacy as topical antivirals, no ocular toxicity, lower cost Stromal Keratitis Most common cause of infectious corneal blindness in the US Form of recurrent herpetic external disease associated with the greatest morbidity Pathogenesis unknown Cell-mediated immunity to corneal antigens up-reglated by HSV Bystander effect of proinflammatory cytokines secreted by infected corneal cells Stromal Keratitis Non-necrotizing/Interstitial: Necrotizing: unifocal or multifocal stromal haze without epithelial ulceration Rare; severe, rapidly progressive, stromal inflammation with epithelial ulceration; may result in perforation Stromal vascularization, scarring Endotheliitis Pathogenesis uncertain but may be due to inflammatory reaction to live virus in the endothelium Corneal stromal and epithelial edema, KPs underlying zone of edema, mild iritis Disciform (most common), diffuse or linear endotheliitis Associated trabeculitis and IOP Management of Stromal Keratitis and Endotheliitis Slow taper of topical steroids is the mainstay Topical Trifluridine QID or Acyclovir 400 mg x5/day Long-term prophylaxis for recurrent disease (ACV 400 mg BID) The Herpetic Eye Disease Study Topical steroids significantly decreased stromal inflammation and shortened duration of stromal keratitis No benefit to addition of oral Acyclovir to topical Trifluridine and Prednisolone in non-necrotizing stromal keratitis Acyclovir does not prevent stromal keratitis or iritis in patients with epithelial keratitis Acyclovir prophylaxis minimizes recurrent disease in patients with stromal keratitis • Barron BA et al. Herpetic Eye Disease Stud. A controlled trial of oral acyclovir for herpes simplex stromal keratitisOphthalmology. 1994 Dec;101(12):1871-82. • Wilhelmus KR et al. Herpetic Eye Disease Study. A controlled trial of topical corticosteroids for herpes simplex stromal keratitis. Ophthalmology. 1994 Dec;101(12):1883-95 • Retrospective study of 87 penetrating keratoplasties in herpetic keratitis at 3 centers in Germany • Analyzed the effectiveness of combined systemic acyclovir and immunosuppressive therapy with cyclosporine A or mycophenolate mofetil • Graft survival rates and functional outcomes in these high risk keratoplasties, when treated with systemic immunosuppression were comparable with results of normal-risk keratoplasties References • BSCS. External Disease and Cornea • Barron BA et al. Herpetic Eye Disease Stud. A controlled trial of oral acyclovir for herpes simplex stromal keratitisOphthalmology. 1994 Dec;101(12):1871-82. • Wilhelmus KR et al. Herpetic Eye Disease Study. A controlled trial of topical corticosteroids for herpes simplex stromal keratitis. Ophthalmology. 1994 Dec;101(12):1883-95 • Kinchington PR et al. Herpes simplex virus and varicella zoster virus, the house guests who never leave. Herpesviridae. 2012 Jun 12;3(1):5 Thank You