HERPES VIRUS Are ubiquitous human pathogen capable of causing bothasymptomatic infection and active disease 2 types – HSV 1 – oropharynxHSV 2 – genital area Ocular disease typically caused by type 1 Causes primary infection in children and neonates Mode Of Infection: HSV 1 – close contact HSV 2 – venereal – birth canal
VIRAL STRUCTURE Double stranded DNA virus Icosahedral shaped capsid surrounding the core Capsid surrounded by an envelop of glycoprotein,carbohydrate and lipids
M/A Receptor specificity and host cell factors determine theability of a particular virus to infect a cell type HSV binds to one or more cellular receptor – heparinsulphate Virus fuses with cell membrane Enters the cell and nucleus where the transcription of viralDNA occurs – protein
M/A HSV DNA alone is infectious Viral DNA begins replication 3 to 4 hrs after infection, withcomplete virion being secreted when infected cell lyse
IMMUNE DEFENSE MECHANISM Both humoral and cellular responses are involved Replication of virus or the alteration of antigenicity ofstromal cells – Autoimmune response HSV can exists as whole virion in stroma & incite aninflammatory response It can enter keratocytes – cause intermittent response Residual viral Ag in corneal transplant – rejection
IMMUNE DEFENSE MECHANISM Endothelitis – endothelium gets infected with HSV – elicits acellular response – cell lysis – shedding in aqueous – iritis Delayed hypersensitivity response – corneal opacity Secretion of glycoprotein – antigenicity of this protein –stimulates the host immune response Immune defense mechanism – local tissue destruction,scarring, & recurrent inflammation
IMMUNOLOGICAL EVENTS OCCURING AT PRECLINICAL PHASE OF HERPETICKERATITS
MECHANISM OF LATENCY AND REACTIVATION After peripheral entry and primary infection HSV travels ina retrograde fashion to various ganglion – TG, cervical,sympathetic, brain stem Here it resides during the lifespan of host Process begins with in 1 to 2 days of primary infection andmay take several weeks to complete The ICPO ( infected cell protein no 0) or junctional region ofviral genome is retained in the host cell nucleus during latentviral state. Reactivation from latency results in production of largeamounts of this RNA, referred to as antisense RNA, & resultsin a cascade of events leading to production of viralpolypeptides and ultimately intact infectious virions.
PATHOGENESIS Factors for reactivation – Sunlight Trauma Heat, abnormal body temperature Other infectious disease Emotional disease
CLINICAL FEATURESSuspicion of viral keratitis arises if there is: Associated skin lesions, recurrences of these lesions Stress-induced recurrence Immunocompromised status History of contact Symptomatic eye with minimal conjunctival and cornealsigns Superficial dendrites with loss of corneal sensation
CONGENITAL AND NEONATAL OCULARHERPES May be acquired by one of the three periods: Intrauterine (5%) Peripartum(10%) Postpartum (85%) Intrauterine infection occurs in 1/300,000 births,with features of microophthalmia, retinal dysplasia,optic atrophy and chorioretinitis. There are also often marked skin, vital organ , andneurologic lesions. HSV infections in latter two periods are furtherclassified as skin, eyes, or mouth (SEM) with orwithout the other involvement seen in intrauterineinfections. Ocular herpes include one or all: conjunctivitis,epithelial keratitis, stromal immune reaction, cataract,necrotizing chrioretinitis.
PRIMARY INFECTION After 6 months – maternal anti-HSV IgG Acute follicular conjunctivitis Keratoconjuctivitis with non-suppurative lymphadenopathy Diffuse punctate keratitis – that evolves into multiplescattered microdendritic figures. As a rule confined to epithelium clinically – d/t lackof previous immunologic stimulus
RECURRENT INFECTION Patients with recurrent herpes have both cellular andhumoral immunity against the virus.
CLASSIFICATION OF HSV KERATITIS The disease may present asany one or a combination ofthe following:1. Blepharoconjuctivitis2. Episcleritis, scleritis3. Infectious epithelialkeratitiscorneal vesiclesdendritic ulcergeographic ulcer(amoeboid)limbal ulcer (marginal)4. Neurotrophic keratopathy5. Stromal keratitisNecrotizing stromalkeratitisImmune (interstitial)keratitisImmune ringsLimbal vasculitisDisciform keratitis6. EndothelitisDisciformDiffuseLinear7. Iridocyclitis8. Trabeculitis
BLEPHAROCONJUCTIVITIS, EPISCLERITIS,SCLERITIS BC is more localized infection than that seen in primarydisease. Vesicles are localised rather than diffuse, starting asred papules that form clear vesicles, break, & scab overto heal without scarring. Conjuctivits is usually diffuse and watery. Episcleritis & scleritis may occassionally occur and areslowly responsive to topical or oral NSIAD’S.
RECURRENT INFECTIONInfectious Epithelial Keratitis(IEK): Corneal vesicle – PEK – within 24hrs, coalesce to formtypical dendritic ulcer Dendritic ulcer – MC presentation Branching linear lesion with terminal bulbs & swollenepithelial borders that contain live virus. The dendritic pattern is due to function of viral linear spreadby contiguous cell to cell movement Double staining pattern: Along the length of lesion – fluorescein Swollen epithelial cells & borders – rose bengal
If corneal examinationreveals dendritic or evengeographic ulceration, theinfectious agent is HSVuntill proved otherwise. In herpes, corneal sensationis reduced in approx 70 % ofthe patient. It is almost never totallyabsent, as often seen inzoster keratitis.
RECURRENT INFECTIONIEK: Geographic ulcer – An enlarged dendritic ulcer Extents through the BM &has scalloped borders Associated with longerduration of symptoms &time of healing May or may not beassociated with use oftopical steroids
RECURRENT INFECTIONIEK: Marginal ulcer – Characterized by its proximity to limbus – more intenseinflammation Typical presentation – inferior stromal infiltrate underlyingthe ulcer & limbal injections – epithelial defect 2 aspects in etiopathology – immune & active viral infection Immune reaction is more long lasting & may require topicalsteroids. These tend to be much more resistant to antiviral therapythan are central herpetic infections. Corneal sensation may remain normal in these marginalulcers.
RECURRENT INFECTIONSequelae of IEK:4 recognized sequelae – Complete resolution Dendritic epithaliopathy Stromal scarring Stromal disease – necrotizing or immune
RECURRENT INFECTIONNeurotrophic keratopathy: Damage to gasserianganglion Impaired corneal innervation Decreased tear secretion Excess use of antiviralsSigns – Irregular cornea with loss ofcorneal luster Characterized by persistentepithelial defect Oval in shape with gray,thickened borders formed byheaped up epithelium unableto move across or adhere tothe damaged ulcer base.
RECURRENT INFECTION Stromal keratitis: Accounts for 2% of initial episodes 20 – 48% of recurrent HSV infection Necrotizing stromal keratitis: Direct viral invasion of stroma C/F – epithelial defect, necrosis, ulceration & denseinfiltration of stroma May lead to thinning of cornea & perforation
RECURRENT INFECTIONStromal keratitis: Stromal immune keratitis (interstitial keratitis): Retained viral antigen within the stroma triggers anintrastromal inflammation. Overlying epithelium is usually intact C/F – stromal infiltration, stromal edema, immune ring,stromal neovascularization & lipid keratopathy Ghost scarring and foot prints May lead to disciform keratitis
RECURRENT INFECTIONStromal keratitis: Immune ring – AAC precipitate Midstroma Complete or incomplete Singular or multiple Central or paracentral Limbal vasculitis: Focal One or more quad may be involved in an edematous,hyperemic reaction sufficiently severe to cause dellenformation. Little/ no tendency of these vessels to invade cornea inabsence of associated interstitial keratitis.
RECURRENT INFECTION Disciform keratitis: Is delayed hypersensitivity reaction to HSV, antigenic changes of thesurface membranes of stromal cells & to the antigenically provocativeresidue of the viral invasion. Primarily, endothelitis occurs, leading to disc form cornealedema due to imbibition of aqueous humour Disk shaped area of stromal edema either central or paracentral,microcystic epithelial edema, KPs, underlying epithelial edema & iritis Folds in DM Corneal sensation , KP’s +nt Raised IOP if associated with trabeculitis.
Stromal neovascularization: At any level of cornea Multiple fronds of NV + intense infiltration Sectoral / all quadrants Aggressive treatment result in complete resolution
RECURRENT INFECTION Lipid keratopathy – Follows neovascularization Further scarring and loss of vision Increased risk of graft rejection
RECURRENT INFECTIONEndothelitis: Inflammatory reaction of theendothelium leading to stromaland epithelial edema Presence of KPs Pathogenesis – immunological –presence of HSV-1 antigen inendothelial cells Types: Disciform Diffuse Endothelitis – entirecornea is involved Linear Endothelitis – line ofKPs on the endothelium thatprogresses from periphery tocenter.
RECURRENT INFECTIONIridocyclitis: Can occur without prior h/o keratitis Fine KPs, AC reaction Posterior synechie Trabeculitis – raised IOP M/A – iris cell invasion by HSV live virus. Posterior segment complications of HSV: Cystoid macular edema, Epiretinal membrane, papillitis,retinal fibrosis and retinal detachment ( 8% HSV, 25 % VZV)
TREATMENT STRATEGIES Clinical Trials In an extensive literature review to determine theefficacy of various antiviral drugs in ocular epithelialherpes, Wilhelmus reported data on 4251 pateints. Hefound the following:1) Acyclovir, trifluridine, vidarabine were better thanidoxuridine for both dendritic and geographical ulcers.2) Other agents such as bromovinyldeoxyuridine,ganciclovir, and foscarnet were equivalent totrifluridine or acyclovir.3) Oral acyclovir was equivalent to topical acyclovirointment & use of the oral form didn’t hasten healingwhen used in combination treatment with a topicalantiviral.
Contd..4) Antiviral agents didn’t increase the speed of healingcompared with debridement, but reduced the risk ofrecurrent epithelial keratitis.5) The combination of debridement with topical antiviralseemed to be better than either treatment alone.6) Combined topical antiviral therapy and interferon wasbetter than an antiviral alone at 7 days, but not at 14days.
TREATMENTPrimary disease – Topical antivirals X 14-21 days Supported by antibiotics and cycloplegics Gentle debridement before application of topical drugs. Primary corneal disease responds slowly but well totherapy, usually heals without scarring because of theabsence of immune reaction.
TREATMENTIEK (Dendritic, geographical ulcers) – Gentle debridement with sterile cotton tipped applicator Acyclovir 400 mg PO 5t/d * 14 days, or Famciclovir 500 mg PO twice daily for 14 days, or Valacyclovir 500mg PO twice daily for 14 days, or Trifluridine 1 % 9t/d for 5 days, then 5t/d for 9 days. Topical antibiotics while the cornea is ulcerated. Cycloplegics , if needed for mild iritis. If not healing think of – neurotrophic keratitis/resistance.
TREATMENTNeurotrophic keratitis – Stop all unnecessary medications Gentle debridement of boggy epithelium Artificial tears Mild steroid : If active stromal keratitis +nt Therapeutic soft CL Doxycycline 100mg PO once daily to inhibit collagenase Cycloplegics: if iritis is +nt Tarsorrhaphy Cyanoacrylate glue – if perforation occurs
TREATMENTStromal keratitis – Necrotizing – topical AV + AB + cycloplegics• Patch graft, conjunctival flapping/glue Immune rings –• Topical steroids + AV• Oral steroids in severe cases
INDICATIONS FOR TOPICALSTEROIDSTopical steroids – Marginal keratitis Mod immunostromal keratitis Mod disciform & diffuse Endothelitis Inflamed neurotrophic keratopathy Mod trabeculitis
INDICATIONS FOR ORAL STEROIDSOral steroids ( along with topical) – Severe immune stromal keratitis Severe disciform & diffuse Endothelitis All cases of linear Endothelitis Severe trabeculitis
INDICATIONS FOR TOPICALANTIVIRALSTopical antivirals – HSV blepharitis HSV conjunctivitis IEK Prophylaxis in steroid treatment of immune stromalkeratitis
INDICATIONS FOR ORAL ACYCLOVIROral Acyclovir – Diffuse endothelitis Severe trabeculitis Linear endothelitis Immunocompromised patients Paediatric patients refractory to topical Prophylaxis against recurrent IEK Prophylaxis for post-PKP with h/o HSV
SURGICAL TREATMENTConjuctival flap: used to quite down an inflamed,ulcerated melting eye.Tarsorrhapy: used as adjunctive therapy to contact lenswhere protection and healing of the recalcitrant ulceratedsurface are the immediate aim.Lamellar keratoplasty: For very sup scarring to restorevision without risk of rejection of full thicknesstransplant.PKPCorneal perforationDense scar
VARICELLA ZOSTER VIRUS Incidence & epidemiology: Spread by saliva droplets, or direct contact withinfected rash. Local inf in nasopharynx viremia & seeding ofRE cells, skin, viscera and ganglia. The maculopapular rash appears in successive crops,lesions of various stages present simultaneously. Contagious period approx 1 day before rash &continues approx 1 week after app of each crop of lesionor until the cutaneous sores crust over. IP: 12- 17 days after contact.
CLINICAL DISEASE Congenital varicella syndrome If mother contracts varicella during first or secondtrimester of pregnancy. Ocular findings may include chorioretinits, optic nerveatrophy or hypoplasia, congenital cataract and HornerSyndrome. Systemic findings may include hemiparesis, bulbarpalsies, cicatricial skin lesions in a dermatomaldistribution, developmetal delay, & learing difficulties. No spec treatment . Vaccinate all women with no history of previousvaricella.
CLASSICAL VARICELLA OCULARFINDINGS Lesions on the lids or on conjunctiva +nt in form ofsmall vesicular or papular eruptions at the limbus. Resolve without difficulty but may rarely turn to veryred, painful, punched out ulcers with sec reaction in theeye. Cornea may develop superficial punctate keratitis orwispy, branching dendritic ulcers without teminalknobs. Less frequently reported varicelaa findings in eye- Irits( occasionally fibrinous), lid necrosis, intersticialkeratitis with neovascularisation, dendritic keratits,neurotrophic ulceration with corneal melting,extraocular muscle palsies, internal ophthalmolplegia,cataract, chorioretinitis, and optic neuritis.
DIAGNOSIS AND TREATMENT Diagnosis based on acute or recent history of systemicds with ocular or periocular involvement with vesicles. Treatment For Acute Disease: Acyclovir 20mg/kg PO 4t/d * 5 d or adult dose of 800mgPO 4t/d * 5d, if pt weight is > 40 kg. Lesions of lid, conjunctiva or cornea ( dendritic or rarelygeographical keratitis) may be ameliorated bytrifluridine applied 9t/d * 7-10 days plus an topical AB. Late onset immune stromal ds treated similar tostromal herpes infection. Steroids not used during acute infection as this mayenhance the viral process. IV acyclovir may be used in severe cases.
HZO First described by Hutchinson in 1865 MC involves ophthalmic division of 5thnerve Frontal branch is MC involved Nasociliary involvement – 76% ocular involvement Hutchinson’s sign – vesicles at the side & tip of nose HZO lies dormant in TG
HZOProdrome – 2 to 3 days of malaise associated with fever, headache& hypoaesthesia with pain & burning in affecteddermatome Release of virus from sensory nerve ending – macularrash which becomes papular & then vesicular within24hrs New vesicles continue to develop x 4 days
HZO Vesicles become filled with turbid yellow fluid orhemorrhage Rash evolves to dry crusts over 2 to 3 wks Hemorrhage –AnticoagulantsHematologic diseaseVasculitis
HZOPathogenesis – VZV transported from epithelial vesicles to sensoryaxons to ganglion satellite & neural cell bodies Can reach from hematogenous spread During latency – continual active transcription Direct correlation between increasing age & HZO Reactivation of VZV in ganglion causes inflammationwith associated ganglion & necrotic changes on dorsalroot ganglion and perineural tissue Mononuclear infiltration & intranuclear inclusions Spreads peripherally & centrally
HZOPathology – Virus travels along the sensory axons to the skin withdemyelination & cellular infiltration of neurons andadjacent blood vessels. Mononuclear infiltration & multinucleated giant cellreaction occur at the level of subepithelial tissues. Virus enters the eye via the ciliary nerves. Perineuritis & perivasculitis around long andshort ciliary nerves and vessels. Epithelial keratitis: due to direct invasion of cells. Stromal keratitis - lymphocyte cell – mediatedresponse to viral antigen.
HZO ZOSTER SINE HERPETE (ZSH)- reactivated VZVthat causes only neurological symptoms such asdermatological neuralgia or neuropathy and onoccasion , ocular inflammation. There is, by definition,no rash.
CORNEAL CHANGESPEK – 2 days Associated with conjunctivitis Characterized by blotchy swollen epithelial cells Coarse PEKs are peripheral, multiple, raised small &focal in appearance & stain with rose bengal
CORNEAL CHANGESPseudodentrites – 4-6 days PEK coalesce to form multiple dendritic / stellate lesionsof swollen raised epithelium Broader, more plaque like and without central ulceration– diff from HSV
CORNEAL CHANGESAnterior stromal infiltrates – 10days Represents reaction to soluble viral antigen / directinvasion Hazy granular dry infiltrate just under Bowman’smembrane
CORNEAL CHANGESKeratouveitis/Endothelitis – 7- 15 days Represents direct viral invasion of endothelium Sudden onset DM folds + stromal + epithelial edema Uveitis ranges from few KPs to severe granulomatousreaction centered around the DM
CORNEAL CHANGESSerpiginous ulceration – 1months Corneal thinning due to limbal vasculitis by immunemechanism Characteristic crescentric shape & peripheral location Vascularization & perforation
CORNEAL CHANGES Sclerokeratitis – 1 month After 1 month of HZO Scleralization, vascularization & stromal thinning orperipheral faceting of cornea
CORNEAL CHANGES Corneal mucous plaques – 2-3month Coarse grey white branching lesions on the surface ofswollen epithelial cells Several months after HZO Can be wiped off the surface leaving abnormal butintact epithelium Neurotrophic or immune mechanism
IRIDOCYCLITIS Ant uveal tract is involved in HZO second only tocornea in frequency. Clinically characterized by symptoms of pain,decreased vision, and photophobia. Signs include ciliary congestion, kp’s and iris edema. In more severe cases there may be ant peripheral andpost synechia formation with a fibrinous exudate. Striate keratopathy, vascular dilation,post syn, sectoralpigment iris atrophy, and sphincter damage may alsobe seen. HZ irits differ from HS irits in that the former is alymphocytic/plasma cell vascultits, whereas the latteris a diffuse lymphocytic infiltrate of the irisstroma( there may be ass ischemic limbal vasculitis)
IRIDOCYCLITIS FFA reveals occulsion of iris vessels at sites ofatrophy. As a result of vasculits and ischemia, zoster iritis, mayalso cause hypopyon, hyphema, heterochromia iridis,sympathetic ophthamia, hypotony, and phthisis 25% pt of HZV uveitis has post pole complications likeCME, epiretinal membranes,papilits, retinal fibrosisand detachment,, whereas only 8% of pt with HSVhave such complications
GLAUCOMA Potential reduction in IOP due to HZ necrosis of ciliarybody and pars plicata may be counterbalanced byimpairement of outflow by pigment and cellular debrisclogging the TM, acute trabecultits, and sec angleclosure caused by ant syn formation. Depending upon the resulting imbalnce the IOP mayrange from abnormally low to marked sec glaucoma. Most common sec complication of VZV uveitis,occasionally requiring surgical intervention. Treatment: topical beta blocker, systemic or topicalCAI’S
Post herpetic neuralgia – Pain that persists after the acute rash of HZ hasabatedResolves within 1yrM/A – preferential loss of large inhibitory fibers inthe nerve with subsequent increase in nociceptivetransmissionEctopic activity in damaged nociceptive fibers
OPHTHALMIC COMPLICATIONS Ramsay Hunt syndrome – 7thnerve palsy + loss of taste over ant 2/3rdtongue + earpain + vesicles in external auditory canal or pinna
OPHTHALMIC COMPLICATIONS In immunosuppressed patient – Skin lesions – Large (10 to 20 mm), multiple, punched out ulcerationwith black eschar and a peripheral rim of vesiculation& positive VZV culture
DIAGNOSIS Morphologic – Tzanck technique: Slide is prepared from the fluid ofthe fresh bullae. Multinucleated giant epithelial cells Pap smear – intranuclear eosinophilic inclusion bodies Immune detection – Elisa, PCR
ACTIVE DISEASE Antivirals( treat for 7 days , starting within 72 hrs) Famcyciclovir 500mg PO TDS Valacyclovir 1 g PO TDS Acyclovir 800mg PO 5t/d Pain prevention TCA’s( eg nortryptyline, desipramine) 25-75 mg PO * 3months Nonnarcotic or short term narcotic analgesic Immunocompromised patients with any zoster – I.V Acyclovir 15 – 20 mg/kg/day30mg/kg/day (disseminated)
TREATMENT Dermal eruption – Astringent Domboros (Burows) solution (aceticacid/aluminum acetate), cool compresses, andmechanical cleansing of the involved skin are helpful. Topical antibiotic ointment may inhibit scarring anddecrease the possibility of bacterial superinfection. Topical corticosteroid ointment should be avoided, atleast during the initial few days after the acutedermatologic crisis, during which active replicatingvirus is present in the epidermis and dermis
TREATMENT Ocular anterior segment:a) Exposure keratopathy: topical antibiotic ophthalmicointment TDSb) Dendritiform keratopathy: therapy 2-3 wk• 3% vidarabine ointment,or• 1% trifluridine 5t/d• Oral antivirals ( as in active ds)c) Immune keratopathy, episcleritis, scleritis, or iritis:• Topical steroids: slow taper• Oral NSIAD’S• Cycloplegics for iritis.
TREATMENT Glaucoma:• Topical beta blockers• No miotics• Topical steroids if glaucoma is due to inflammatorytrabeculitis.
TREATMENT Chronic/recurrent ds:a) Dendritiform, or immune keratopathy, episcleritis, scleritis, iritis• Same as acute dsb) Tennuous, hazy epithelium in anaesthetic cornea• Early lateral tarsorraphy and lubrication with artificial tear andtear ointment.• Allow vascularisation to progress to aid in healing any ulcer.• Topical steroids with caution and only at low doses to minimizeany inflammationc) Exposure keratopathy or corneal ulceration or thinning• Lateral tarsorrhapy• Therapeutic soft contact lens• Tissue adhesive for progressive thinning• Conjuctival flap, transplant, or keratoprosthesisd) Glaucoma• Treat same as acute ds
TREATMENT Postherpetic neuralgia:• TCAs ( eg nortryptyline, desipramine) : 25mg titratedupto 75mg. Caution if pt has cardiac ds.• Gabapentin: 300mg PO bd.• Slow release opoids added if TCAs +/- gabapentin notsufficiently effective• Capsaicin cream TDS• Lidocaine skin patches or cream, 12 h on, 12hr off painfulskin area• Frontal or nasal nerve block• Trigeminal ganglion ablation contraindiacted
HEDS IPurpose To evaluate the efficacy of topical corticosteroids intreating herpes simplex stromal keratitis in conjunctionwith topical trifluridine. To evaluate the efficacy of oral acyclovir in treatingherpes simplex stromal keratitis in patients receivingconcomitant topical corticosteroids and trifluridine. To evaluate the efficacy of oral acyclovir in treatingherpes simplex iridocyclitis in conjunction withtreatment with topical corticosteroids and trifluridine
HEDS IResults Patients who received prednisolone phosphate dropshad faster resolution No apparent benefit in the addition of oral acyclovir tothe treatment regimen of a topical corticosteroid and atopical antiviral. Benefit in adding oral acyclovir to the treatment of HSViridocyclitis in patients receiving topical corticosteroidsand trifluridine prophylaxis
HEDS IIPurpose To determine whether early treatment (with oralacyclovir) of herpes simplex virus (HSV) ulcerations ofthe corneal epithelium prevents progression to theblinding complications of stromal keratitis andiridocyclitis. To determine the efficacy of low-dose oral acyclovir inpreventing recurrent HSV eye infection in patients withprevious episodes of herpetic eye disease. To determine the role of external factors (such asultraviolet light or corneal trauma) and behavioralfactors (such as life stress) on the induction of ocularrecurrences of HSV eye infections and disease.
HEDS IIResults No benefit from the addition of oral acyclovir to treatmentwith topical trifluridine in preventing the development ofstromal keratitis or iritis. Study found that the risk of stromal keratitis oriridocyclitis was quite low in the year following an episodeof epithelial keratitis treated with topical trifluridinealone.
ADENOVIRUSKERATOCONJUCTIVITIS Medium-sized (90–100 nm), nonenveloped (without anouter lipid bilayer) icosahedral viruses composed of anucleocapsid and a double-stranded linear DNAgenome. 47 known serotypes, classified into six subgroups( Athrough F) acc to hemagglutination. In 1889, the first description of an adenoviral ocularepidemic given by Fuchs in Austria. The most severe ocular disease is usually noted Ipatients with Ad 8 adenoviral infection. Use of tonometer on sequential patients withoutadequate sterilization after use on one pt, infectedwith adenovirus, can cause epidemic
EPIDEMIC KERATOCONJUCTIVIS Serotype AD 8, 19, & 37. Most serious adenoviral ocular illness is EKC. Acute ocular ds usually attacks young adults duringthe fall and winter months U/L in 2/3rdpt EKC differs from PCF in that latter is far morecommonly associated wit systemic illness and b/l ocularinvolvement. IP 8 days Sign and symptoms: Acute tearing, FBS, photophobia, followed by lid andconjuctival edema and hyperemia, follicular andpapillary conjuctival response with or without hge ormembrane formation, & tender LN’s
Lid edema may become so severe as to resemblecellulitis. Dry eye or symblepharon formation may be long termsequela of this conjuctival damage. Severe pain comes with development of keratitis,which occurs in approx 80% pt and begin around eightday after onset of acute ds. There occurs marked discomfort, pain, photophobia,lacrimation and blepharospasm.
STAGES OF EPK Stage 1: diffuse, fine, superficial epithelial keratitiscaused by live virus. Stage 2: occur after 1 wk, coalescence of above lesions tofocal, punctate, slightly raised, whitish epithelial lesionsthat stain with fluroscein. Stage 3: after 2 weeks, all replicating virus has beenterminated by the host immune response, and within afew days the epithelial lesions become combinedepithelial and subepithelial areas. Stage 4: chacterized by subepithelial, whitish macularlesions or nebulae that no longer stain with fluroscein.
EKC typically involves central cornea in clumps or rowsof macular opacities, but may reach the periphery andmax density by the third or fourth week of illness. Occasionally, lesions coalesce to form scallop edgednummular opacities 1-2 mm in dia that in severe casesmay mimic HSK.
PHARNGOCONJUCTIVAL FEVER Serotype Ad 3 and 7 Similar to EKC except that the keratitis is usaully mildand b/l, and subepithelial infiltrates are less frequentand more transient.
NONSPECIFIC FOLLICULAR CONJUCTIVITIS Serotype Ad 1,2,4,5,and 6 NFC may be caused by any of the ocular adenovirus,but is usually sufficiently mild not to be seen in theophthalmology OPD. Because keratitis does not develop and the conjuctivitsremains mild, these pt are usually treated bypediatricians or family physicians.
CHRONIC ADENOVIRALKERATOCONJUCTIVITIS Serotype Ad 2,3,4 and 19. Uncommon, often recognized cause of disturbing antsegment inflammatory and scarring ds. Syndrome characterized by prolonged exacerbation oftearing, redness, and photophobia. Sequale of either active epithelial keratitis, recurrentconjuctivits with sub epithelial opacities or chronicpapillary conjuctivitis.
DIAGNOSIS Cytologic scrappings that reveal mixed lymphocytic andneutrophil infiltrate and degenerated epithelial cells. Giemsa staining for inclusions may reveal earlyeosinophillic intranuclear bodies. Other rapid laboratory diagnostic test: Immunofluorescense EIA ELISA Electron microscopy
TREATMENT Antivirals are ineffective , except cidofovir. Topicals NSIAD’S : relief of inflammation. No effect onviral replication or appearance of corneal infiltrates. Cycloplegics as needed for iritis. Topical antibiotic ointment to lubricate and protect thecorneain presence of membranes. Ice packs, antipyretics and dark glasses as needed. Washing hand frequently. For truly debilitating visual disturbance or loss,usemild topical steroids to relieve symptoms and infiltratestemporarily. Symptoms may reoccur if steroids tappered, stopped