Yong Meng Hsien Lecturer & Ophthalmologist, UKM & HCTM, Malaysia yongmenghsien@ppukm.ukm.edu.my Last edited: Feb 202

1. Herpes & Eye
Dr Yong Meng Hsien
Lecturer & Ophthalmologist, UKM & HCTM
yongmenghsien@ppukm.ukm.edu.my
Last edited: Feb 2022

2. Virology for ophthal
• small (10–400 nm in diameter)
• Basic unit: nucleic acid + capsid (protein)
• Capsid-genome interaction: stabilize & protect virus/capsid, express
ligand for host-cell binding or act as Ag in membrane to neutralize Ab.
• Types:
• DNA vs RNA
• dsDNA: herpes, hep B
• ssRNA: HIV, corona, Zika
• Single vs double stranded (for RNA)
• Lipid envelope (+glycoprotein) or non-enveloped
• Enveloped (e.g HIV/Herpes): >vulnerable to ext environment/UV/alcohol & >short lived if
out fr host, but +latency inside host
• Non enveloped (e.g adeno): >resist/need dilute bleach
• Antiviral:
• Target gene transcription (depend nuclei acid type)
• Aciclovir: -DNA polymerase, activated by thymidine kinase

3. Herpesviruses @Eye
• dsDNA & enveloped
• Human as only reservoir (HSV)
• Seroprevalence: age & socioeco
• Sero-ve can still infective (ganglia harbouring- trigeminal &
dorsal root)
• Primary ifx (viral shed/contact of fluid/lesion) →
latency (different sites) → reactivation
• Latency @ sensory ganglia: HSV1/2/VZV
• Latency @ B lymphocyte (EBV)
• 6 out of 8 related to eye
– HSV1 (>necrotizing IK vs HZV, >orofacial)
– HSV2 (>genito-urinary)
– HZV (>ARN @old/PORN/necrosis PU/vasculitis vs HSV)
– CMV (>vessel involvement/hrge, <vitritis VS HSV/HZV)
– EBV
– Kaposi sarcoma associated KSHV (human herpesvirus 8)

5. Part 1- HSV
• World endemic/human as only reservoir
• Transmission: direct contact (secretion/lesion) esp@
crowding/poor hygiene/high age
• Acquisition – replication – neuron transport – dorsal root
ganglion e.g. trigeminal
• HSV 1 >orofacial, 2>genital
• Direct infection- epithelial (conj/eyelid/cornea)
• Immune reaction- stromal, uveitis
• Ix principle: immunodiagnostic methods, viral culture,
PCR. +- serology
• Treatment principle: thymidine/DNA synthesis, DNA
polymerase (virus specific), thymidine kinase

6. Part 2- HSV
• Ocular involvement & classification
• Primary infection, reactivation, recurrence
• Sight threatening conditions & complications
• Red flags @ paeds, atopic, HIV, bilateral
• DDx
• Investigation
• Treatment (relative risks of antiviral & steroid)
• Prevention: recurrence and after ocular surgery (PK/cataract)
• Specific terms: HEDS, ghost dendrite, ghost vessels, necrotizing,
metaherpetic, geographical
• Controversies: epiT debrideM, antiviral treatment-topical VS
oral-tapering-prophylaxis, topical steroid choice-dose-regime-
@necrotizing stromal K, disciform K vs uveitis + corneal
decomp, long term/lifelong antiviral

7. HSV VS VZV in general
• VZV/HZ > uveitis Cx esp ARN in old pt/PORN/vasculitis
• HSV > corneal Cx esp necrotizing IK
• Keratitis:
• Dendrite: bulb (HSV) vs taper (VZV) end
• HSV  HEDS
• VZV  ZEDS (pending)

9. HSV
HSV1/2 (above/below waist), primary ifx (very common-by contact/virus shed) → dormant @
axon/ganglion (latent)  recurrence/reactivation + 2nd inflam
Intraocular Systemic
•Lid/Conj: vesicular blepharoconj/follicular conj
•Keratitis: reduced sensation, epiT dendritic/bulb K (stain edge
RB/central F), stromal K (IK/DK/+-necrotizing), endotheliitis
• Corneal late Cx: neurotrophic/metaherpetic/bullous/lipid K/scar
• AU: diffuse fine KPs, iris atrophy (sectoral), high IOP, recur!
• Primary/reactivation
- skin CN V (incomplete
dermatome)
- cold sore
• genital
• ARN (young pt/immuno-good/w encephalitis/skin HSV)- 5 criteria:
PanU, retinitis (peripheral/well margin/2-3mth to necrosis),
peripheral to center, occlusive vasculitis (A), rapid progress.
• neonate (fr genital
tract)- skin/MM/
encephalitis
❖ Rx (EpiT K): topical aciclovir 5x/topical trifluridine 1% 8x/oral aciclovir 400mg 5x for 2/52
❖ Rx (stromal K ): topical trifluridine 8x/oral aciclovir 400mg BD + gutt steroid 2H taper wkly KIV prophylx
❖ Rx (AU): T Aciclovir 400mg 5x/day (FamC 250mg TDS/ValA 1g BD better) + gutt steroid KIV prophylx
❖ Rx (ARN): IV Aciclovir 10mg/kg TDS x 2wk then oral 800mg 5x/day for 2-3mth, IVT GanC/foscarnet,
steroid (24H aft), laser retinopexy, aspirin
❖ Rx (prophylaxis-recurrence/post PK): 400mg BD for 12mth (recurrence less 50%)

10. HZV
- Direct invasion  chicken pox  dormant @dorsal root of CN sensory ganglia  shingles
- 2nd inflammation causing stromal K/vasculitis/uveitis/scleritis
Intraocular Systemic
• Congenital: cataract/microphthal/OD
• Keratitis- reduced sensation + epiT (dendrite/taper)/
stroma (numular/interstitial)/endoT (disciform)/AU
• Scleritis: most! +-necrotizing
• AU: fine KPs, iris atrophy, high IOP, recur!
• Skin HZO shingles –
complete dermatome, never
BL (Hutchinson’s sign)
• Cx: post herpetic neuralgia
• PORN (immuno-down/aggressive BUT min AU/IU/vasculitis
(vessel sparing)/inflam/hge!)- 3stages: early macula retinitis
(cherry red spot), middle necrosis, late scar (cracked
mud)/RD/OD atrophy
• ARN (old pt/immuno-good): >panU/inflam/vasculitis
>artery/hrge/well margin retinitis fr periphery (vs PORN)-
4stages: retinitis-vitritis-pigment change-RD/OD atrophy)
• HZO without dermatitis =
zoster sine herpete
• Chickenpox- eye involved if
immuno-down
• Congenital- mental,
limb/skin deform, death
❖Ix (ocular): tap for viral PCR
❖Rx (corneal epiT): occ aciclovir 3% 5x/day (or oral to avoid toxicity)
❖ Rx (stromal K): gutt steroid (watch ED) + topical aciclovir/oral BD dose (prophylaxis)
❖ Rx (AU): T Aciclovir 800mg 5x/day x 1wk (T valA 1g TDS), Gutt steroid, KIV prophylaxis
❖ Rx (PORN/ARN): IV aciclovir 10mg/kg TDS 2wk, IV/IVT GanC/Foscarnet + HAART + steroid
❖ HZO: T aciclovir start within 72H reduce severity/eye involve 50%/neuralgia

11. CMV
h PU= AIDS defining (CMV retinitis)- CD4 <50, natural history 5R
h AU= immuno-good pt (+- a/w FHU/Posschner SS)
Intraocular Systemic
• AU: like HSV/HZV (+failed aciclovir)
• IU: mild (except IRU)
•PU (3 forms & 3 zones I-III: 2DD fovea+1DD OD-till equator-rest)
-Fulminant/classical (hrge): pizza pie/cheese & ketchup along
arcade >central > necrosis
-Indolent (granular): periphery (90%), less
aggressive/inflam/vasculitis
• no Sx in immuno-
competent
• CNS
• Lung
• Skin
-Frosted branch angiitis 6% (++sheathing)
• Cx: OD/CMO/vasculitis/retinal necrosis (atrophy/hole/RD 50%)
• congenital: cataract/microphthal/PU/OD
• CMV keratitis (>endothelitis)
• Congenital: intracranial
calcification, mental,
deaf, microcephaly,
jaundice/HSM,
❖ Ix (systemic): CD4/RNA load (HIV status)
❖ Ix (ocular): vitreous PCR
❖ Rx: HAART vs IRU, aim CD4 100-150 for 3-4mth,
❖ Rx: oral valganciclovir 900mg BD 3-6wk then OD (SE- BMS, need GCSF/filgrastim),
GanC (IV 5mg/kg BD 2wk then OD/IVT 2mg/0.1ml biweekly x 3wk then weekly/IVT implant
8mth), foscarnet (IV/oral/IVT, SE renal, IV foscanet 90mg/kg BD 2wk then OD), cidofovir (IV/oral
weekly then fortnightly, SE renal), steroid if IRU, laser if break (no role for prophylactic)
❖ screen: CD4 <50 (q3mth), 50-100 (q6mth), >100 (yearly)

12. HZO

13. Terminology for HZV
• Varicella-Zoster Virus (VZV)
• Infection: chicken pox vs HZ/shingles
• Vaccine: varicellae vs HZ vaccine
• Varicella = Chicken Pox  primary VZV infection
• eyelid vesicles and follicular conjunctivitis
• Zoster = Shingles  reactivation
• Reactivation of latent VZV @dorsal root ganglia results in a localized painful
cutaneous rash
• Zoster sine herpete (shingles without skin findings)
• HZ Ophthalmicus (HZO)
• HZ @ ophthalmic division of the trigeminal nerve
• Hutchinson’s sign
• cutaneous vesicles at the side of the tip of the nose
• nasociliary nerve involvement
• greater likelihood that the eye will be affected

14. HZV- Part 1
• Primary ifx: direct contact with VZV skin lesions or
respiratory secretions via airborne droplets and is
highly contagious for naive individuals.
• Latency @sensory ganglia and
• 20% of reactivates later
• mostly thorax T3 through L3 dermatome
• 15% involve 5th CN > V1 = HZO  70% ocular involvement
(nasociliary, frontal, or lacrimal branches)
• Specific term: Hutchison

15. HZV- Part 2
• HZV VS HSV
• Varicella VS Zoster (disease/vaccine)
• HZV @ immunosuppressed

16. HZO
• VZO/Herpesvirus type 3 (alpha)
• reactivation/dormant @ neurosensory/CN or spinal root/trigeminal
ganglia (V1)
• Risk: immunity down/trauma/surgery/radiation/old
• HZ (unilateral/neurocutaneous/dermatome)
• Dermatomal rash
• Neuropathic pain
• Pre-eruptive, acute eruptive, chronic (neuralgia)
• Hutchinson/long ciliary fr nasociliary nerve
• Keratitis, uveitis, trabeculitis, retinitis (ARN/PORN), occlusive vasculitis,
focal choroiditis
• Scleritis/epiS, cicatricial lids/ocular surface/lacrimation unit
• Immuno-down: >HZO, >severe, >dermatome, >recur/chronic, +-
systemic dissemination  need IV Rx

17. HZO Ocular surface & Others
• Eyelid vesicles
• The vesicles typically crust and will heal within 2-6 weeks.
• Conjunctivitis (HZ or secondary bacterial)
• Episcleritis
• Scleritis
• NeuroOphthal: Oneuritis, papillitis, neuroretinitis, CN palsy, 4-fold
increase in ischemic stroke, encephalitis, meningitis, intracranial
vasculitis
• Orbital e.g. orbital apex syndrome
• Chronic recurrent HZ
• Post herpetic neuralgia (PHN)
• +-Bilateral in immunosuppressed or atopic eye dz or paeds

18. Mx- HZO
• Antiviral
• 7–14 days with acyclovir 800 mg 5x OD, valacyclovir 1g TDS, famciclovir 500 mg
TDS
• IV Acyclovir 5-10 mg/kg TDS for 5 days
• Reduce ocular complication
• Reduce pain duration +- PHN
• Earlier better (<72H), but later still beneficial (esp new vesicles)
• Chronic/recurrent +- extend to 4wk Rx, or prophylaxis with Acyclovir 400mg BD
• Systemic corticosteroids
• Controversial & must together with antiviral
• T. prednisolone 40 mg OD tapered over 3 week
• Accelerate the rate of cutaneous healing and alleviation of acute pain
• Not affect/reduce PHN
• Pain relief for PHN
• amitriptyline 25 mg PO ON or Pregabalin 150mg /day

19. • Oral acyclovir (800 mg 5 times daily for 10 days)
• Oral famciclovir (500 mg 3 times daily for 7 days)
• Oral valacyclovir (1000 mg 3 times daily for 7 days)
• VZV vaccination: 50yo-59yo
• Varicella zoster immune globulin is available for
postexposure prophylaxis

20. Mx- VZV uveitis & stromal keratitis
& keratouveitis
• Oral antiviral (=HZO)
• Topical steroid
• Cycloplegic
• Antiglaucoma (avoid PGA)
• Chronic/Multiple relapse- long-term, low-dose
topical corticosteroids and maintenance therapy
with acyclovir 400 mg BD-TDS, valacyclovir 1g BD,
or famciclovir 500 mg TDS

21. Herpetic Viral Keratitis

22. • Epithelium: marginal K, Ghost dendrite/image (subepiT scar fr prev
healed epiT ulcer)
• Stroma: with or without neoV
• Endothelium: linear, diffuse
• Keratouveitis, uveitis/retinitis (AU/PU), trabeculitis
• Optic neuritis
• Blepharoconjunctivitis (follicular/no PSM +LN) +- epiT
• Systemic: asym, URTI, vesicular dermatitis

23. HSVK
• Relative risks of antiviral & steroid
• Primary Ifx: conjunctivitis > blepharitis > keratitis +- URTI
• Reactivation: keratitis > conjunctivitis/blepharitis +- skin
vesicular dermatitis, > severe/>stromal K
• Different layer = different pathoG (direct infection vs
immune mediated) = different Rx (antiviral +- steroid)
• Corneal sensation, dendritic, geographical, infiltrate, edema,
disciform, ulcerative, necrosis, KPs, AC cells, IOP
• Paeds >severity, >recurrence, >blinding Cx, >bilateral (20 vs
10%), >risky (amblyopia)
• Risk factor: viral virulence, host defence/age, atopic dz
(>severe/bilateral/resistant to Rx), topical/ocular
inflame/trauma/drops (PG/steroid), HIV >recur (same
severity)

24. HSV keratitis- sight threatening
• Stromal scarring
• Thinning with perforation
• Ulceration
• NeoV with lipid K
• Astigmatism
• Endothelial dysfunction
• Prolonged steroid use with Cx
• Cumulative effects with recurrences
• Greatest morbidity: Stromal K! esp if recurrent! Worse
if necrotizing!

25. VZV Keratitis
• Epitheliopathy
• SPK  microdendrite  dendritic with taper end
• corneal epithelial mucoid plaques
• Stromal keratitis
• > nummular keratitis
• < necrotizing IK vs HSV
• Endotheliitis/disciform keratitis < HSV
• Neurotrophic keratitis & Metaherpetic > HSV

26. Complication of viral keratitis
• Epitheliopathy
– D2 prolonged topical antiviral (toxicity)
– diffuse SPK + conj injection
• Neurotrophic K
– SPK +- vortex K/chronic epithelial regeneration lines → frank
neurotrophic ulcers (no RB stain, round/oval @central/inferior cornea,
edge roll under/gray/elevated
– Focal/diffuse depends severity/recurrences
– Rx lubricant ++ → tarsorrhaphy
• Metaherpetic K
– active or resolving HSV IK + chronic ED (no RB stain)
– D2 devitalized stromal
• Bullous K
• Lipid K
– With deep stromal vascularization
– Rx: topical steroid

28. DDX- Dendritic keratitis
Ifx:
• HSV (bulb end)
• VZV (taper end)
• Adenovirus/EBV (uncommon)
• Acanthamoeba
Non ifx:
• epithelial regeneration line
• neurotrophic K
• Thygeson K
• soft contact lens wear (thimerosal)
• topical med (antivirals/B-blockers)
• epithelial deposits (iron lines, Fabry
disease, tyrosinemia type II, systemic
drugs)
DDX- Interstitial keratitis
• HSV
• VZV
• Acanthamoeba
• syphilis
• EBV/mumps
• Lyme disease
• sarcoidosis
• Cogan syndrome
DDX- Necrotizing keratitis
• HSV
•microbial keratitis
(bacteria, fungi, or
acanthamoebae)
• retained FB
• topical anesthetic
abuse.
Stromal keratitis
• Stromal K: nonnecrotizing (interstitial or disciform) or necrotizing
• Interstitial K: uni/multifocal stromal haze/whitening w/out ED/ulcer/epiT edema
• Disciform K: primary endotheliitis with corneal stromal and epithelial edema in a oval
shape, KPs underlying the edema
• Necrotizing K: suppurative corneal inflammation with ED eccentric to the infiltrat (ED
edges not stain with rose bengal) with stromal vascularization

29. Ix
• Samples: vesicle fluid/conj swab (primary), cornea epiT scrap/Aq fluid
(reactivation)
• Test: immunodiagnostic methods, viral culture, and PCR +- serology
• HSV-1 epithelial viral culture with viral transport media
• avoid rose Bengal (viricidal), before antiviral, long time (10d), low sensi 75%,
high spec
• Direct fluorescein antibody (DFA)- 85% sensi n spec, corneal swab
smeared on slide
• PCR- corneal epithelium or tear film, high sensi near 100% (false +ve
shedding without ifx), low spec
• ELISA- low sensi high spec
• Serology- limited, can be latent, negative serology but active HSVK
(negative serology = less likely HSVK)

30. Ifx
Inflam
Pain
Cx
Vision
Recurrence
Treatment Principle

31. Rx
• HSVK- epithelial-K
• Oral or topical antiviral
• Topical: acyclovir occ 3% OR ganciclovir gel 0.15% 5x, till healed then 3x for extra 1wk,
• Topical (old): trifuridine gutt 1% q2h (9x) till healed then 5x for extra 1wk (ocular toxicity if
>3wk)
• Oral: acyclovir 400mg 5x 7-10days, valaciclovir 500mg BD (caution: TTP/HUS if
immunoC/liver d/o), famciclovir (caution: nephrotoxic esp CKD/elderly >65yo w CNS
SE)(pregnancy class B, safe for neonate)
• No benefit: combine oral/topical, debridement (+-gentle one if drug R)
• HSVK- stromal-K
• Topical steroid q2-4H (taper 1-2wkly total atleast 10wk) + oral aciclovir (prophylaxis dose
BD fr starting or therapeutic dose 5x then taper according to gutt steroid)
• Alternative: topical cyclosporine (replace steroid) 0.05-2%
• If +ulceration/ED: oral acyclovir 800mg 5x 7-10days and limited topical steroid (BD) from
beginning
• Topical steroid >1drop OD = need prophylaxis
• HSVK- endothelial-K
• Same as stromal-K: antiviral therapeutic dose then taper, response faster, not need
prolonged Rx course
• Paeds/atopic dz/geographical ulcer- consider higher dose/longer duration
(800mg 5x 14-21days)
• Renal dose: If CrCl <25 TDS, <10 BD
• New: interferon

32. Others: topical antiviral
• trifluridine is effective in treating HSV keratitis, it has
low bioavailability and causes ocular surface toxicity
• Acyclovir- no available
• Ganciclovir is a newer synthetic medication with more
broad-spectrum antiviral coverage. Just as effective as
acyclovir, while causing less ocular toxicity. It also may
be less likely to promote drug resistance
• generally use oral antivirals to avoid ocular toxicity that
can complicate topical therapy and obscure the clinical
picture. We reserve topical medications for adjuvant
treatment when oral medications are not adequate or
in patients who are not good candidates for systemic
therapy.

33. HEDS
• USA
• 6 key points (5 clinical trials + 1 epidemio study)
• Epithelial K, stromal K, antiviral Rx/prophylaxis,
occurrence & recurrence
• Risk of recurrence: same type >stromal K, past
episodes, short interval in btw, immune status vs
virus virulence
• Limitation of study: near all treatment arms on
topical trifluridine (not oral or topical acyclovir)

34. HEDS I & II
• HSV stromal K → use topical steroid (pred 1% q3h and
taper over 10wk) + topical anti-viral (aciclovir/trifluridine)
– No role of systemic acyclovir on top of topical steroid+trifuridine
– Topical steroid need to taper at least 10wk
– Topical antiviral full dose till healed then half dose extra 1wk
– 400mg BD 1yr to reduce recurrence x 50% (32 to 19%)
• HSV iridocyclitis → use oral aciclovir (400mg 5x/day x
10/52) on top of topical steroid+trifuridine
• HSV epiT K → use topical antiviral only
– No role of oral acyclovir on top of gutt trifuridine
– No to use topical steroid
• Triggering factor → unsure (stress/CL/environment)

36. HEDS
• 6 studies (5RCT 1epidemio)
• Epithelial VS Stromal K
• Incidence & recurrence > @ epi K
• Risk of recur for stromal K: prev stromal K, high
frequency, short interval
• Risk of recur epi K: prev either epi or stromal K

37. Zoster Eye Disease Study (ZEDS)
• prolonged suppressive oral antiviral treatment with
valacyclovir reduces complications (eye disease and
neuralgia PHN)
• 1 year valacyclovir

38. HED vs cataract op
• significant period of inactivity should be considered before cataract surgery- 3-6mth (if
only epiT dz +- just 6wk)
• Oral antiviral prophylaxis in the immediate perioperative period, especially while under
treatment with corticosteroids
• but no change in routine postoperative steroid use is needed.
• In prev severe dz (severe iritis, stromal K)-
• acyclovir 400 mg 5x 2D before surgery and then continued for 2W postoperatively +-
topical antiviral, such as ganciclovir 0.15 percent gel (Zirgan) or trifluridine 1 percent
solution (Viroptic)
• More severe: pre 5x for 1wk + post 5x for 2wk then 2x for 3-6 months
• If severe intraocular inflammation or recurrent herpetic disease develops
postoperatively, add 80 mg/day of oral prednisolone for one week (unless
contraindicated). Add a topical antiviral (ganciclovir or trifluridine) if it is not already in
use.
• Prophylaxis with topical ganC 2D + 2W for epithelial dz
• For topical regimens of five or more drops of prednisolone acetate 1.0% or equivalent a
day, we use full antiviral dosing of acyclovir 400 mg PO five times a day; for regimens of
three or four daily drops we do one-to-one frequency matching of the topical and oral
medication; and, for regimens of two or fewer drops, we utilized the standard
prophylactic dose of 400 mg PO BID.

42. Prevention of HSVK
• Mainly for stromal K
• More complication if recurrence
• Epithelial K not benefit in prevent stromal K
• Oral antiviral > benefit then topical
• T. Aciclovir 400mg BD x 1yr
• Lifelong for severe recurrent stromal K, only eye,
corneal transplant cases
• Alternative
• Aciclovir 800mg TDS wk/mth then 400mg BD x 1yr
• Valaciclovir 500mg OD or 250mg BD x 1yr
• Famciclovir 250mg BD x 1yr

43. Endothelitis
• Inflam vs Ifx (or mixed)
• Ifx >virus (CMV/HSV/HZV/mumps)
• DDX: Posner-Schlossman, FHI
• CMV
• >Immunocompetent, not responded to aciclovir
• coin-shaped KPs (in cluster) +- edema/high IOP/AU
• 4 forms (based on edema + KPs)- linear, sectoral, disciform,
diffuse
• Ix: Aq PCR, Goldmann-Witmer coefficient >3 (local
production of CMV antibody)
• Mx: topical ganC + systemic valGan (BD 6/52 then OD
6/52 at, atleast) & topical steroid

44. Interstitial K
• Def: stromal inflam (without primary endo/epiT inflam)
• Patho: immune mediated reaction
• Causes:
– Ifx: TB/syphilis/leprosy/herpes/onchocerciasis/Lyme
– Non-ifx: Cogan (a/w PAN/deaf), sarcoidosis
• SSX:
– Mid stromal opacity (late): feathery scarring with ghost vessels
– Mild stromal inflam (acute): limbitis, stromal vascularization/ bleed,
salmon patch, AU
– TRO granulomatous ifx (AU/KPs)
– TRO congenital syphilis (BL, onset 5-25yo, AR pupil & salt pepper
fundus)
– TRO Cogan dystrophy (BL, young, autoimmune vasculitis with
deaf/tinnitus/vertigo/CTD/retinal vasculitis)
• Mx:
– Screening for CTD/ifx
– Topical steroid +- AB (underlying ifx)

45. Herpetic/Viral AU

49. AU: recurrent + UL + non ifx+-viral/non systemic/non panU
1. Lens related (phacolytic/anaphylactic)
• Phacoanaphylactic- granulomatous/type III? immune complex hyperS (B cell/Arthus), +- bacteria/SO
related (1-24days post trauma)
2. Trauma related
3. FHI
• EpiD: young-middle age, +-related to rubella/CMV > HSV
• SSx: asymptomatic/white eye + recurrence AU + not response to steroid
• KPs: fine stellate diffuse KPs (white/non pigment) + no PS/PAS
• Iris: heterochromia/atrophy (moth eaten), +-Koeppe nodule +- abn iris vessel @angle (rubeotic-like)
bleed on surgery (Amsler’s sign), iris crystals/Russel bodies (plasma cells filled with antibodies)
• cataract >PSCC 70%, Glaucoma 20%, dust-like uveitis
4. Posner Schlossman/Glaucomatocyclitic crisis
• EpiD: young-middle age, +-related to CMV/HSV
• white eye + min KPs, but very high IOP (40-50mmHg) with corneal edema
• no PS/PAS/rarely uveitis
5. Viral AU (VAU): HSV, HZV, CMV, rubella
• Unilateral, white eye/low grade AU, recurrent
• IOP + cornea + iris
• AAU/CAU, Posner Schlossman, FHI, endothelitis
• PCR & Goldmann-Witmer coefficient analysis on the aqueous humor

50. VZV uveitis
• VZV uveitis
• More @HZ (33%)- 2-4wk aft onset HZO, > granulomatous
• Less @Primary ifx (25%)- if immunosuppressed, paeds, in-
utero, within 1wk aft onset of HZO, > non-granulomatous
• Herpetic AU- KPs inferior cornea, patchy iris atrophy
• Trabeculitis with high IOP
• HZV >ARN @old/PORN/necrosis PU/vasculitis (vs
HSV)

51. Anti-Herpetic Medications

54. HZO
• VZO/Herpesvirus type 3 (alpha)
• reactivation/dormant @ neurosensory/CN or spinal
root/trigeminal ganglia (V1)
• HZ (unilateral/neurocutaneous/dermatome)
• Dermatomal rash
• Neuropathic pain
• Pre-eruptive, acute eruptive, chronic (neuralgia)
• Hutchinson/long ciliary fr nasociliary nerve
• Keratitis, uveitis, trabeculitis, retinitis (ARN/PORN)

55. • Oral acyclovir (800 mg 5 times daily for 10 days)
• Oral famciclovir (500 mg 3 times daily for 7 days)
• Oral valacyclovir (1000 mg 3 times daily for 7 days)
• VZV vaccination: 50yo-59yo
• Varicella zoster immune globulin is available for
postexposure prophylaxis

56. Crystalline K (Ifx vs non-ifx) & Vortex K
• Non-ifx
– Lipid deposit: Schnyders CD
– Mineral deposit: argyrosis (silver), Band K (calcium), Chrysiasis (gold)
– Protein deposit: cystinosis, dysproteinemia (multiple myeloma)
– Medication deposit (topical): gutt ciloxan
– Medication vortex K: amiodarone, tamoxifen, phenothiazines/chlorpromazine,
indomethacin, chloroquine + Fabry dz (ask ABCDE)
• Deposit @epiT/radiating below pupil axis/BL
– Idiopathic: crystalline dystrophy of Bietti
• Ifx
– Suboptimal inflam response to microb
• >gram +ve/rare/indolent/>strep viridans/epidermitis/fungi
• > post PK eye with long term topical steroid
– SSx: stromal opacities (branching/grey-white/slow progress)
– +- intact/ED, +- min inflam
– Rx: c&s, topical Ab (weeks)

57. Corneal Edema
• EndoT dysfx (barrier/pump)
• Causes
• Age
• IOP
• Post op (PBK/ABK)
• Phaco 4-10% cell loss /complicated/IOL touch/IOP
• Prevent: dispersive OVD, stable IOP, BSS plus (glutathione)
• Uveitis/inflam
• FED/PDS/PEX/KC with hydrops
• Signs
• EpiT: haze/microcyst/bullae
• Stroma: thicken/wrinkle (Waite-Beetham line)
• DM: fold
• EndoT: pseudo/gutta
• Post collagenous layer (retrocorneal membrane)
• Mx
• Hypertonic saline/pain relief/BCL
• EndoT transplant

58. Neurotrophic K
Causes
• Physio
• age
• Systemic
• DM
• Leprosy
• Riley Day
• Ocular
• CD (lattice/Reis B)
• CL
• Topical eyedrop
• Post op (PK/Lasik/ECCE)
• HSV/HZV

59. Recurrent Corneal Erosion (RCE)
• Intro: EpiT BM-ant stroma-epiT disturbance  break down
• Physio: basal cell mitosis & reform BM 
hemidesmosomes/anchoring fibril/plaque (6mth)
• Causes:
• Injury: sharp/superficial/clean/linear cut (paper/nail)
• PED/LSCD-like: chemical/burn/FB/CL/eyedrop
• Spontaneous: CD (epiT/bowman/ant stroma), DM
• SSx: awakening pain/BOV/ED-pseudodendritic healing-scar
• Mx:
• Surface protection: AT/lubricant/BCL >8wk, wake-up eye close
• Restore adhesion: debridement, diamod burr polish Bowman, ant
stromal puncture ( 0.1mm depth till ant stroma, 75-100 holes), PTK
(phototherapeutic keratectomy with spot mode), Nd YAG laser
Bowman micropuncture

60. Persistent Epithelial Defect (PED)
• Intro: sterilization vs healing phase @keratitis, wound
healing physio
• Cause:
• Dz: ifx/inflam/tumour
• Surface: neurotrophic/exposure/dry/LSCD, toxic/rub
• Systemic: DM
• Mx
• Reduce inflam (steroid)
• Reduce toxicity (topical drug/preservative)
• Promote healing need GF/ECM (AT/autologous/cord
serum/AMT/gutt tetrapeptide)
• Surface protection (BCL/tarrsorraphy/gutt NAC)

61. Herpetic Endothelitis

62. Key features
• linear keratic precipitates similar to endothelial
rejection, bilateral recurrent corneal edema, and mild
iritis
• CMV: coin shaped/cluster KPs
• viruses was detected in the corneal endothelium,
aqueous humor, and trabeculae
• In vivo laser confocal microscopy has shown that the
corneal endothelial cells of patients with CMV
endotheliitis exhibit a high reflection area surrounded
by a halo of low reflection (owl’s eye morphological
features)

63. Causes
• Autoimmune
• Viral Ifx
• HSV, VZV, mumps, CMV
• Idiopathic

64. CMV Endothelitis
• Topical administration of ganciclovir eye drops is used
as a combination therapy with systemic treatment and
a prophylactic therapy for long-term use
• systemic drugs (ganciclovir or valganciclovir)
• both 0.5% and 1.0% ganciclovir eye drops stored light-
shielded at 4°C and 25°C were stable in appearance,
concentration, and pH for 6 weeks
• storage in a refrigerator should be encouraged.
• issues of limited shelf stability, high pH, and the
potential risk of microbial contamination of ganciclovir

65. • diagnostic criteria for CMV endotheliitis based on a
viral examination by PCR of aqueous humour, in
combination with clinical manifestations
• Japan Corneal Endotheliitis Study Group ( JCESG)
• Commonly diagnosed with anterior uveitis and
ocular hypertension prior to confirmation of CMV
endotheliitis. Coin-shaped lesions were observed in
70.6%, and linear keratic precipitates in 8.3%,
anterior chamber inflammation was detected in
67.9%
• most common in middle-aged and elderly men

67. • ganciclovirfor intravenous infusion (DENOSINE®) or
0.15 % ganciclovir gel (Virgan®), which are approved for
HSV keratitis
• Ganciclovir (DENOSINE® 500 mg for I.V Infusion,
Mitsubishi Tanabe Pharma Co.) was used to prepare
0.5% and
• 1.0% solutions for use as eye drops. A 500 mg sample
of
• ganciclovir was diluted in 10 ml sterile water in laminar
flow
• hood, and then diluted in 50 ml to prepare 0.5%
solution
• and in 100 ml sterile saline to prepare 1.0% solution.

68. • Stability, safety, and pharmacokinetics of ganciclovir
eye drops
• prepared from ganciclovir for intravenous infusion
• Naoki Okumura1
• Ganciclovir (DENOSINE® 500 mg for I.V Infusion,
Mitsubishi Tanabe Pharma Co.) was used to prepare
0.5% and 1.0% solutions for use as eye drops. A 500 mg
sample of ganciclovir was diluted in 10 ml sterile water
in laminar flow hood, and then diluted in 50 ml to
prepare 0.5% solution and in 100 ml sterile saline to
prepare 1.0% solution

69. • . When we make a diagnosis of CMV
• endotheliitis, we administer a systemic anti-CMV treatment. In most
• cases, we perform ganciclovir injection twice-daily for 2 weeks. When
• the intravenous injection of ganciclovir is not available,
• valganciclovir tablets are used for 4-12 weeks. Our treatment also
• includes 0.5% ganciclovir eye drops (hospital prepared) and
• low-concentration steroid eye drops. If 0.15% Gancyclovir-gel (Virgan
• gel) is approved for HSV keratitis in your country, you can use Virgan
• gel. We don't have experience to use 2% gancyclovir eye drops by
• ourselves. We use GCV eye drops for long term to prevent the
• recurrence. If you have any questions, please let me know.

70. Topical Ganciclovir
• Gel ganC 0.15%: Virgan, Zirgan
• Herpetic keratitis: 5x till healed (10-14days) then TDS for 7 more days, or 5x per
day for 6wk
• Tolerated better then acyclovir ointment
• Ointment acyclovir 3%: Zovirax
• Herpetic keratitis: 5x till healed (10-14days) then TDS for 7 more days, or 5x per
day for 6wk
• Gutt ganC varying concentration (0.15 – 0.5 – 1 – 2%)
• CMV AU or endothelitis
• Different regime:
• 2hourly for 2wk then taper weekly
• 5x per day for 6wk
• (+-systemic oral valgan 4-12wk or IV ganC 2wk)
• (+- intravitreal ganC if PU)
• Clinical response (expected after 1wk): VA, IOP, KPs, AC inflam
• Local irritation

71. Herpes Zoster & Eye
YMH 2020

72. Vaccination for Shingles
• IndC
• >60yo for Zostavax (single dose, live, effective for 5yr)
• >50yo for Shingrix (two doses, 2-6 mth apart, non-live, effective 15yr &
efficacy 90%)
• Regardless prior shingles
• Regardless prior HZ (as long as not during acute ifx) but should have
eye examined within several weeks before and after vaccination
• ContraIC
• Immunosuppressed (live vaccine)
• Pregnancy (atleast 4wk after vaccine)
• Ideally if+ prior chicken pox/varicella ifx  then only benefit from
HZ vaccine  but presume all >50 yo had varicella exposure so no
need Hx/Ix
• If on antiviral chronically  stopped 1 day before through 2
weeks after the vaccine is given.
• Can same time with pneumococcal & influenza vaccines
• 50% reduction in incidence of zoster and a 66% reduction in PHN

73. Vaccination for Chicken Pox
• 2 doses, 90% effective
• Vaccinated against chickenpox may still get the
disease. However, it is usually milder with fewer
blisters and little or no fever
• Paeds: first dose at 12-15 months old and a second
dose at 4-6 years old
• AAO: recommended for anyone older than 12
months without a history of chickenpox or with a
negative serologic test result

76. CPG 2014