Types of viral keratitis, diagnosis of different types and management of each. Clinical evaluation with images described. Standard treatment protocols given.
3. Introduction
Infective keratitis is characterised by corneal infiltrate which
may be associated with epithelial defects and/or signs of
inflammation
Global incidence of HSV keratitis is roughly 1.5 million
Incidence of corneal ulcer found in a study in South India was
113 per 1,00,000 population per year i.e. 8,40,000 affected
annually
45 million corneal blind worldwide, with an addition of 1.5-2
million each year, out of which 40,000 is attributed to viral
keratitis
Mohod PN, Nikose AS, Laddha PM, Bharti S. Incidence of various causes of infectious
keratitis in the part of rural central India and its visual morbidity: A prospective hospital-based
observational study. J Clin
Ophthalmol Res 2019;7:31-4.
4. As per census 2011 and rapid assessment of avoidable
blindness survery, conducted by the Ministry of Health and
Family Welfare, 0.1% (1.22 lakh) are bilateral and 0.9%
(10.98 lakh) are unilateral corneal blind in India.
Early recognition with prompt diagnosis and rapid institution
of appropriate therapy will significantly improve visual
prognosis.
Mohod PN, Nikose AS, Laddha PM, Bharti S. Incidence of various causes of infectious
keratitis in the part of rural central India and its visual morbidity: A prospective
hospital-based observational study. J Clin Ophthalmol Res 2019;7:31-4.
5. Epidemiology
Viral keratitis is the most common form of keratitis in
developed countries
Impact in developing countries still not well established
Herpes Simplex
keratitis
Varicella Zoster
induced keratitis
Adenoviral keratitis
Cytomegalovirus
keratitis
6. HSV Keratitis
DNA virus, Herpes viridae family
2 types – HSV type 1 and type 2
HSV 1 is the most common type, affecting the upper body -
causing cold sore/fever blister on face, mouth and also
affecting the eye
HSV 2 causes genital Herpes and may occasionally cause
ocular Herpes
Acharya M, Dave A, Farooqui JH. Commentary: Herpes keratitis: A diagnostic challenge.
Indian J Ophthalmol 2019;67:1046-7.
7. Farooq AV, Shukla D. Herpes simplex epithelial and stromal keratitis: an epidemiologic update.
Surv Ophthalmol. 2012;57(5):448–462.
8. A study conducted by Kaul et al. in North India estimated the
incidence of HSV1 as 33.3%.
A tertiary hospital based study from central India, over 2
years found prevalence of viral keratitis to be around 17% of
the total cases of keratitis
Mohod PN, Nikose AS, Laddha PM, Bharti S. Incidence of various causes of infectious
keratitis in the part of rural central India and its visual morbidity: A prospective
hospital-based observational study. J Clin Ophthalmol Res 2019;7:31-4.
9. The disease may occur bilaterally in 11.9%
More common in atopes and immunosuppressed
Recurrences are common
- 27% at 1 year
- 50% at 5 years
- 57% at 10 years
- 63% at 20 years
Recurrence caused by the same strain
Epithelial keratitis have epithelial recurrence and stromal
keratitis have stromal recurrence
Young RC, Hodge DO, Liesegang TJ, Baratz KH. Incidence, recurrence, and outcomes of
herpes simplex virus eye disease in Olmsted County, Minnesota, 1976-2007: the effect of
oral antiviral prophylaxis. Arch Ophthalmol. 2010;128(9):1178–1183.
10. Pathophysiology
Herpes is a large virus, 150-200 nm size.
Has a double stranded DNA core
Humans: the only natural reservoir
Sources of infection - direct contact with infected lesions
- salivary droplets
- fomites
- iatrogenic: unwashed hands,
contaminated tonometer head
11. 1. Primary infection in areas of
Vth nerve distribution
6. New corneal infection
12. Virus may remain in a latent phase, acting as a potential
source of recurrent disease and also responsible for the
donor-derived HSV in transplanted corneas.
Triggering agents for reactivation
- fever
- ultraviolet exposure
- psychological stress
- ocular trauma
- immunocompromised
15. Retrospective data including 220 eyes, over 5 years
Presenting complaints
- pain: 50%
- redness: 50%
- defective vision: 56%
Indian J Ophthalmol 2006;54:23-7
16. Infectious Epithelial Keratitis
Due to live virus
The incidence of new epithelial keratitis: 5.6 per 100,000
New + recurrent = 15.6/100,000
Symptoms - watering
- photophobia
- irritation
- blurred vision
Punctate keratitis: Punctate/stellate
raised whitish opacities due to
swollen, virus laden cells.
Farooq AV, Shukla D. Herpes simplex epithelial and stromal
keratitis: an epidemiologic update. Surv Ophthalmol. 2012;57(5):448–462.
17. Dendritic keratitis: Swollen epithelial cells enlarge and coalesce to
form branching dendrites.
- Epithelial sloughing in the centre leads to dendritic ulcer
- Linear branches with terminal bulbs
- Raised edges, contain live virus
- Usually central/paracentral
- Anesthesia in the area of ulcer
- Staining: Flourescein stains the length of ulcer while Rose
Bengal
stains devitalised swollen epithelial cells at ulcer border
19. Neurotrophic epithelial keratitis
Trophic/Metaherpetic ulcer
Chronic post-herpetic corneal inflammation
No active virus
Causes - impaired corneal innervation
- poor tear film
- chronic use of topical
anti-virals
Round/oval shape
Thickened & rolled up margins
‘Reverse staining’ with
Rose Bengal stain
20. D/d – Geographical ulcer
Neurotrophic ulcer Geographical ulcer
History of recurrent
attacks
Always present Maybe present
Duration Long duration(indolent) Short duration
Location Interpalpebral area Variable
Size Constant over a period
of time
Increases or decreases
depending on success
of treatment
Margins Shallow, clean Raised, greyish, has
virus laden devitalised
cells
Rose Bengal stain Margins not stained Margins stained
Anti viral drugs Worsen Promote resolution
21. HSV Stromal Keratitis
2% of primary cases
New stromal keratitis: 0.6/100,000
20-48% of recurrent cases
New+recurrent stromal keratitis = 2.6/100,000
May occur as stromal inflammation primarily or as a
consequence of epithelial keratitis/endothelitis
Symptoms - pain
- blurred vision
Farooq AV, Shukla D. Herpes simplex epithelial
and stromal keratitis: an epidemiologic update. Surv Ophthalmol. 2012;57(5):448–462.
22. Immune mediated Stromal
keratitis
Called Interstitial keratitis
Most common form of stromal keratitis
Type III immune reaction to viral antigen: deposition of
antigen-antibody complexes in stroma
Clinical features - stromal infiltration
- neovascularisation
- corneal thinning
- epithelium intact except in cases where
stromal involvement is secondary to epithelial
keratitis
24. Necrotising Stromal Keratitis
Less common
Direct invasion of stroma by HSV
Active viral replication
Intense stromal inflammation
Can occur if steroids given without antiviral cover
Clinical features - corneal necrosis
- ulceration
- epithelial defect
26. HSV Endothelitis
Delayed Hypersensitivity reaction (type IV) to Herpes
antigen
Cell mediated response
Location of KPs
and presence
of edema
Disciform
Keratitis
Diffuse
Endothelitis
Linear
endothelitis
27. Disciform keratitis
Most common form of Endothelitis
Disc shaped area of stromal edema overlying few KPs
without corneal infiltration
Central/paracentral
Symptoms - watering
- photophobia
- blurring
Associated trabeculitis/uveitis
may occur
Edema and KPs out of proportion
to AC inflammation
28. Diffuse
Endothelitis
Rare presentation
Immune reaction against the
corneal endothelium
KPs scattered over entire cornea with diffuse stromal edema
Associated Iritis present
Linear Endothelitis
Line of KPs on endothelium
Progresses centrally from limbus
Edema between line of KPs and limbus
29. HSV trabeculitis and iridocyclitis
Present as recurrent nongranulomatous anterior uveitis
Is an immunologic reaction to the virus
Circumlimbal ciliary flush, KPs, cells and flare in
aqueous
High IOP: d/t Iritis and TM clogging
Can serve as a diagnostic hallmark
Recurrent episodes: iris atrophy,
synechiae formation and Iris haemorrhages
Candy cane hypopyon: spontaneo
hyphaema mixed with hypopyon
30. Inflammatory Ocular Hypertension
Syndrome (IOHS)
Sudden elevation in IOP in setting acute or recurrent Uveitis
Causes - compromised outflow due to trabecular clogging
- chemical mediators in aqueous
- response to corticosteroids
Herpes infection is recognised as the most common cause
31. Diagnosis
Ocular Herpes Simplex is diagnosed mainly on clinical
examination
Lab investigations may be done for atypical cases
1. Cytology: Giemsa staining
- can be performed in necrostising keratitis
- Multinucleated giant cells seen: Cowdry A cells
2. Viral DNA detection: PCR
- samples from tear film/corneal scrapings
- sample collection should be done before staining: Rose
Bengal toxic to virus
32. Virus isolation: Viral culture
- definitive diagnosis
- culture inoculation of sample swabs
- typical cytopathic effect in 2-4 days, can take upto 10 days
Antibody detection: ELISA/IFA
- can differentiate primary infection from first recurrence
- paired sera tested: first sample 3-4 days after infection and
second after 4 weeks
- low titres in 1st sample and 4-fold rise in 2nd: primary
infection
- moderate titres in 1st sample and 4-fold rise in 2nd:
recurrence
33. Subhan, S., Jose, R. J., Duggirala, A., Hari, R., Krishna, P., Reddy, S., & Sharma, S.
(2004). Diagnosis of herpes simplex virus-1 keratitis: Comparison of Giemsa stain,
immunofluorescence assay and polymerase chain reaction. Current Eye Research.
209–213.
34. Medical management
Antiviral Route Dosage Mechanism
Trifluridine Topical 1% solution
2 hourly
Inhibits viral thymidylate
synthase
Acyclovir Topical
Oral
3% ointment
200/400mg
tablets
5 times/day
Activated by viral
thymidine kinase inhibit
DNA polymerase
Valacyclovir Oral 1000mg
3 times/day
Activated by viral
thymidine kinase inhibit
DNA polymerase
Ganciclovir Topical 0.15% gel
5 times/day
Activated by viral
thymidine kinase inhibit
DNA polymerase
Valganciclovir Oral 900mg
2 times/day
Prodrug of Ganciclovir
35. Herpes Eye Disease
Study(HEDS)
To study the role of adding topical corticosteroids and oral
antivirals with Trifluridine in Herpetic keratitis
HEDS-I consisted of three randomized, placebo-controlled
trials
HEDS-II consisted of two randomized, placebo-controlled
trials and one epidemiologic study that investigated the risk
factors, including stress, for the development of ocular
recurrences of the disease
36. Stromal
keratitis not
on steroids
trial
Stromal
keratitis on
steroids
HSV
iridocyclitis
on steroids
HED
S I
• Topical steroids along with topical antivirals in
stromal keratitis
• Faster resolution and fewer failures
• Oral Acyclovir alongwith topical antivirals and
steroids
• No apparent benefit
• Oral Acyclovir alongwith topical antivirals
and steroids
• Apparent benefit seen
37. HSV
Epithelial
Keratitis trial
Acyclovir
prevention
trial
Ocular HSV
recurrence
factor study
HEDS II
• Role of early Oral Acyclovir alongwith topical
antivirals in progression to stromal keratitis and
iridocyclitis
• No additional benefit
• Efficacy of low dose oral Acyclovir(400 mg BD) in
preventing recurrence of ocular HSV
• Reduced incidence of epithelial and stromal recurrence
by 41%
• 50% reduction in occurrence of more severe infection la
•12 months of oral antiviral prophylaxis is effective in
preventing both epithelial and stromal keratitis recurrenc
• Role of external factors such as corneal trauma
and
behavioral factors such as stress in recurrence
• No statistically significant external factors lead to
recurrence
38. Epithelial Keratitis Dendritic Geographical
Therapeutic dose of topical antiviral OR oral antiviral
Topical Trifluridine 1%
OR
Ganciclovir gel 0.15%
OR
9 times/day x 7 days
f/b tapering
Not to extend beyond 21
days
5 times/day until healing f/b
3 times/d for 7 days
9 times/day x 7 days
f/b tapering
Not to extend beyond 21
days
5 times/day until healing f/b
3 times/d for 7 days
Oral Acyclovir OR 400mg 5 times/d x 7-10
days
800mg 5 times/d x 14-21
days
Oral Valacyclovir OR 500mg 2 times/d x 7-10
days
1gm 3 times/d x 14-21 days
39. Stromal Keratitis Without Ulceration With Ulcer
Therapeutic topical
steroid & prophylactic oral
antiviral
Limited topical steroid &
therapeutic oral antiviral
Topical Prednisolone
1%
PLUS
8 times/d with tapering
over 10 weeks depending
on response
2 times/d
(No clinical data to support
duration)
Oral Acyclovir OR 400mg 2 times/d 800mg 3-5times/d x 7-10d
Oral Valacyclovir OR 500mg 1 time/d 1gm 3 times/d x 7-10d
Oral Famciclovir 250mg 2 times/d 500mg 2 times/d x 7-10d
Endothelial Keratitis
Therapeutic dose of
topical steroid PLUS
therapeutic dose of oral
antiviral
Prednisolone 1% 6-8
times/d f/b tapering to
response (no data to
support duration)
Acyclovir 400mg 3-5 times/d
OR
Valacyclovir 500mg 2times/d
OR
Famciclovir 250mg 2 times/d
40. Prophylaxis of recurrent HSV
keratitis
Indications
Acyclovir 400mg 2 times/d OR
Valacyclovir 500mg 1 time/d OR
Famciclovir 250mg 2 times/d
ATLEAST ONE YEAR DURATION
Multiple recurrences especially stromal
keratitis
Recurrent inflammation with scar reaching
optical axis
>1 episode of HSV keratitis with
ulceration
Post-keratoplasty, when performed for
HSV related scarring
Post-op in h/o ocular HSV
H/o ocular HSV during
immunosuppressive therapy
41. 394 patients, over 32 years with a mean follow up of 7.7
years
175(44%) received oral prophylaxis
Relative risk of recurrent ocular HSV for patients not being
treated with oral antivirals
- Epithelial keratitis: 9.4
- Stromal keratitis: 8.4
42. Role of Cyclosporine
Cyclosporine 0.05% has been effective in treating herpes
simplex virus stromal keratitis, particularly cases that are not
responsive to topical prednisolone
A role for topical cyclosporine in patients with HSV stromal
keratitis without ulceration has been shown in case series
using 2% cyclosporine
Useful as adjunctive therapy to replace or reduce the need for
topical corticosteroids in patients with concurrent HSV stromal
keratitis without ulceration and steroid-induced glaucoma
Useful as a steroid minimizing adjunct in the treatment of HSV
stromal keratitis
43. Medical management: Neurotrophic
ulcer
Aim: Protect damaged Basement Membrane
Stop topical anti-virals
Copious lubrication with preservative free artificial tears
Non healing ulcers: BCL application
44. Medical management: Viral keratotouveitis
Topical Prednisolone 1% 6-8 times/d
Oral Acyclovir 400mg 2 times/d
Topical cycloplegic
Lubricant eyedrops
IOHS - Oral carbonic anhydrase inhibitors
- First line IOP lowering: Beta blockers
Topical Alpha agonists
Prostaglandin analogues avoided d/t risk of viral
reactivation
Kesav, N., Palestine, A. G., Kahook, M. Y., & Pantcheva, M. B. (2019).
Current Management of Uveitis-associated Ocular Hypertension and Glaucoma. Survey of Oph
45. Surgical management
Indications
- Necrotizing keratitis
- Corneal scarring
- Persistent epithelial defect
- Severe neurotrophic keratitis
Conjunctival
flap and
pedicle
Amniotic
Membrane
Grafting
Lateral
Tarsorraphy
Keratoplasty
- Penetrating
- Lamellar
Tuli, S., Gray, M., & Shah, A. (2018). Surgical management of herpetic keratitis.
Current Opinion in Ophthalmology, 29(4), 347–354.
46. Conjunctival flap and pedicle
graft
Non healing neurotrophic ulcer
Small perforations
Corneal melt
Pros Cons
Promotes rapid epithelialization Iatrogenic stem cell deficiency
Provides vital growth factors Obscures view of cornea and AC
Scarring in area from where flap
picked
Accompanying vascularisation: high
chances of PK failure in future
Poor cosmetic result
Tuli, S., Gray, M., & Shah, A. (2018). Surgical management of herpetic keratitis.
Current Opinion in Ophthalmology, 29(4), 347–354.
47. Lateral Tarsorraphy
Persistent epithelial defects
Decrease ocular surface exposure
reducing tear film evaporation
90% of epithelial defects resolve within 18 days
Degree of lid closure can be modified based on the severity
of corneal disease
Can be used as an adjunct to keratoplasty
Limitation: poor cosmetic result
Tuli, S., Gray, M., & Shah, A. (2018). Surgical management of herpetic keratitis.
Current Opinion in Ophthalmology, 29(4), 347–354.
48. Amniotic Membrane Grafting
Refractory neurotrophic keratitis
Non healing epithelial defects
Severe neurotrophic keratitis with stromal melting:
multilayered approach
Studies have demonstrated rapid epithelial healing and
reduced stromal inflammation
Limitation: risk of infection
Structural support
Epithelial and nerve growth
factors
Epithelial cell migration and
adhesion
Anti-VEGF
Supress angiogenesis and
inflammation
Tuli, S., Gray, M., & Shah, A. (2018). Surgical management of herpetic keratitis.
Current Opinion in Ophthalmology, 29(4), 347–354.
49. Keratoplasty
10–20% of all penetrating or anterior lamellar transplants are
done for complications of herpes keratitis in developed
nations
Tectonic: perforation/corneal melt
Optical: scarringPenetrating Keratoplasty Deep Anterior Lamellar Keratoplasty
Can be performed in deep scarring
and endothelial involvement also
Only useful for superficial scarring
Tectonic purposes in perforation No role in perforation
No entrance in AC
Avoids endothelial rejection
More utilisation of donor corneas
Lower rates of recurrence and graft
failure
Tuli, S., Gray, M., & Shah, A. (2018). Surgical management of herpetic keratitis.
Current Opinion in Ophthalmology, 29(4), 347–354.
50. PKP without Acyclovir
prophylaxis
PKP with Acyclovir
prophylaxis
Recurrence at 1 year 39-46% 0-5%
• 2 main reasons for graft rejection after PK are recurrence and
allograft rejection
• Recurrence rate has been found to be inversely proportional to
the length of treatment with oral Acyclovir
- One year post PK recurrence rate in patients receiving
prophylaxis for one year 0-5% as compared to 30% in patients
who received only three week prophylaxis
• Advantageous to treat patients for at least a full year with
prophylactic oral antivirals since most recurrences of HSV
keratitis occur in the first year after keratoplasty
https://www.aao.org/clinical-statement/herpes-simplex-virus-keratitis-treatment-guideli
51. 3 trials reviewed, 126 participants, oral acyclovir vs placebo
after corneal grafting for HSV
Duration of oral therapy: 6 months or more
Dose varied from 200 to 800mg in the studies
23 fewer cases of HSK recurrence per 100 corneal graft
operations if oral acyclovir is used
13 fewer cases of graft failure per 100 corneal graft operations
if oral acyclovir is used
This review concluded that use or oral Acyclovir may lower
risk of recurrence of herpetic keratitis in the first 1 year of
keratoplasty
52. Peer reviewed literature search, including 11 comparative
studies
Evaluated 481 DALK and 501 PK eyes
Conclusions - DALK equivalent to PK in Best Corrected Visual
Acuity
- DALK superior in preserving Endothelial Cell
Density
- More safety with DALK: no entry in AC, no
endothelial rejection
DALK is a good option when Endothelium not compromised
Medicine (Baltimore). 2016;95(39):e4892.
53. Emerging therapies
1. CRISPR/cas9 system
- derived from adaptive immunity
system of bacteria
- the CRISPR/Cas system utilizes RNA
peptides to degrade the genetic
material of viruses
- using this system, the bacterial Cas9
nuclease and a guide RNA (gRNA)
are transferred into cells
- CRISPR systems have been shown to
modify the genomes of HSV-1
and inhibit their replication in vitro
- holds promise for viral replication
inhibition and also role in elimination
of latent infections
54. Two viral genes-targeting gRNAs, designated HSV-1-erasing
lentiviral particles: HELP
Retrograde transportation of HELP from corneas to trigeminal
ganglia
Evidence of HELP modulating herpes reservoir
Yin D, Ling S, Wang D, Yao D, Jiang H, Paludan SR, et al. Intracorneal delivery of HSV-targe
CRISPR/Cas9 mRNA prevents herpetic stromal keratitis. bioRxiv 2020.
55. 2. Humanized antibodies
- humanized monoclonal antibody against the viral glycoprotein
gB
- in vitro studies show neutralisation of wild and drug resistant
HSV 1
- prophylactic and therapeutic use: protection against herpes
simplex encephalitis in immunodeficient mice
- reduced the viral load in mouse eyes when given between 24
hours pre-infection and 56 hours post-infection
- may hold promise in immunocompromised individuals and in
drug resistant HSV
Bauer, D.; Alt, M.; Dirks, M.; Buch, A.; Heilingloh, C.S.; Dittmer, U.; et al. A Therapeutic Antiviral Ant
Inhibits the Anterograde Directed Neuron-to-Cell Spread of Herpes Simplex Virus and Protects aga
Ocular Disease. Front. Microbiol. 2017, 8, 2115.
56. Ophthalmology 2017;124:160-169
• Evaluation of Quality of Life using questionnaires
in patients with unilateral and relapsing HSV
keratitis with controls
• Factors evaluated: General health, vision,
ocular pain, self image and several others
• Even during quiescent phase, unilateral and
relapsing HSK keratitis significantly impaired
Quality of life similar to that of vision threatening
disorders
• Decreased vision has greatest impact on quality
of life, other factors such as frequent relapses
also play a major role
58. Herpes Zoster Ophthalmicus
Varicella Zoster Virus is a member of Herpes virus family,
causing Varicella(Chickenpox) : primary form
Shingles : recurrent form
Herpes zoster ophthalmicus (HZO) is defined as zoster within
the ophthalmic division of the fifth cranial nerve
Incidence: 3.2-4.2 per 1000 population per year
HZO accounts for 10-20% of HZ case
Older age group and immunocompromised more prone
The rash of chickenpox begins as macules and progresses to
papules, vesicles, and then pustules that dry, crust over, and
may leave scars
Tran KD, Falcone MM, Choi DS, et al. Epidemiology of Herpes Zoster
Ophthalmicus: Recurrence and Chronicity. Ophthalmology. 2016;123(7):1469–1475.
59. The ocular manifestations are uncommon in varicella but common
in ophthalmic zoster
Zoster begins with prodromal symptoms, followed by rash.
If the vesicles are present on the side and tip of the nose
(Hutchinson's sign), the external division of the nasociliary branch is
affected : probability of involvement of eye 76%
Koshy E, Mengting L, Kumar H, Jianbo W. Epidemiology, treatment and prevention of
herpes zoster: A comprehensive review. Indian J Dermatol Venereol Leprol 2018;84:251-62
PATHOPHYSIOLOGY: Primary infection virus remains dormant in sensory
ganglion
reactivation
replication in nerve cells and shedding of
virus down axons to skin supplied by that
ganglion
Inflammation and blisters
Intense pain due to perineuritis
61. Skin lesions in varicella zoster (Medical Photographic
Imaging Centre, Royal Victorian Eye and Ear Hospital, Melbou
A: Stromal keratitis
B: Disciform keratitis
C: Nummular keratitis
Babu, K., Mahendradas, P., Sudheer, B., Kawali, A.,
Parameswarappa, D. C., Pal, V., & Philips, M. (2017). Clinical P
of Herpes Zoster Ophthalmicus in a South Indian Patient Popul
Ocular Immunology and Inflammation, 26(2), 178–183
62. Dendrite: terminal bulb Pseudodendrite: no terminal bulb, poor
staining with flourescein, stuck on appeara
63. Complications
Acute retinal necrosis: in immunocompetent host
- acute onset, severe retinal inflammation, causes RD in
almost half
Progressive outer retinal necrosis: immunocompromised
Focal choroiditis
Papillitis/retrobulbar neuritis
Cranial nerve palsies, most commonly IIIrd nerve
Post herpetic neuralgia: Pain lasting more than 3 months
after HZO episode
- risks: older age, more severe rash, ophthalmic involvement
- Allodynia: characteristic, non-noxious such as blowing wind
causes pain
- quality of pain variable: sharp/shooting/tender/burning
64. Management
Systemic anti-virals reduce virus shedding from skin lesions,
reduce chances of dissemination and decrease severity of
ocular complications
If therapy initiated within 72 hours, duration of post herpetic
neuralgia and risk of ocular involvement is also decreased
Standard anti viral therapy is oral Famciclovir 500mg TDS/
oral Valacyclovir 1gm TDS/ oral Acyclovir 800mg 5times/day
for 7-10 days.
Intravenous Acyclovir (10mg/kg every 8 hours) is given in
immunocompromised, to prevent disseminated infection
The American Journal of Medicine (2017) 130, 21-26
65. Oral steroids are recommended alongwith with anti virals as
they reduce pain during acute phase
Topical steroids used in uveitis, stromal keratitis
US-FDA has approved Zostavax for individuals of age 60 yrs
and above
- shown to decrease the incidence of herpes zoster and
postherpetic neuralgia by 61% and 66.5%
CDC has also recommended Varicella zoster immune
globulin for post-exposure in immunocompromised or those
who cannot be vaccinated(neonates,pregnant)
- to be given immediately after Varicella exposure or within 10
days
The American Journal of Medicine (2017) 130, 21-26
66. Adenoviral Keratitis
Causes epidemic keratoconjunctivitis, mainly by serotypes
8,19,37
Highly contagious, transmitted by infected hands and fomites
8 days incubation period
U/L conjunctivitis
B/L affection
Feature - follicular keratoconjunctivitis
- lid edema
- pre-auricular lymphadenopathy: pathognomic
- hemorrhagic conjunctivitis
Corneal trauma facilitates infection
67. Stage 1: corneal epithelial vesicle like elevations
are present which are 25 to 30 microns and
barely perceptible on slit lamp
Stage 2: lesions coalesce and involve deeper
epithelium. Form the classic epithelial punctate
keratitis, visible on slit lamp
Stage 3: faint subepithelial infiltrates visible
behind punctate keratitis
Stage 4: nummular opacities which may be
present months to weeks after the initial episode
69. CMV keratitis
Double stranded DNA virus of Herpes viridae family
Spread – saliva, sexual contact, breastfeeding
Occurs in immunocompetent
Studies show upto 96% pts have h/o topical steroids
Reported to cause Epitheliitis, stromal keratitis and
endothelitis
Endothelitis is the most commonly encountered manifestation
of CMV keratitis
Can be associated with anterior uveitis and ocular
hypertension
Classical findings of CMV Endothelitis: Corneal edema,
keratic precipitates and coin shaped lesionsFaith, S. C., Durrani, A. F., & Jhanji, V. (2018). Cytomegalovirus keratitis.
Current Opinion in Ophthalmology, 29(4), 373–377
70. CMV causes endothelial cell loss, thus early diagnosis and
management is crucial
Diagnostic criteria for CMV endotheliitis
- PCR positive for CMV DNA and negative for herpes
simplex virus (HSV) and varicella zoster virus (VZV)
- either corneal endotheliitis with coin-shaped lesion and/or
linear keratic precipitates
OR
- localized edema and keratic precipitates
- any 2 of the following: recurrent anterior uveitis, ocular
hypertension, or lowered corneal endothelial cell count
Faith, S. C., Durrani, A. F., & Jhanji, V. (2018). Cytomegalovirus keratitis.
Current Opinion in Ophthalmology, 29(4), 373–377
71. Owl eye inclusion bodies on
Confocal microscopy
Kobayashi, A., Yokogawa, H., Higashide, T., Nitta, K., & Sugiyama, K. (2012).
Clinical Significance of Owl Eye Morphologic Features by In Vivo Laser Confocal Microscopy in
Patients With Cytomegalovirus Corneal Endotheliitis. American Journal of Ophthalmology, 153(3),
72. Treatment
Mainstay of treatment: systemic Ganciclovir
- Oral valganciclovir 900 mg twice a day for six weeks
followed by 900 mg every morning for six weeks
Found to be resistant to oral Acyclovir, oral Famciclovir and
topical Acyclovir
In a large case series, the combination of systemic and
topical ganciclovir 0.15% was found to be more effective
CMV is a chronic infection and CMV endotheliitis recurs in 5–
60% of eyes
CMV can also cause corneal graft failure: 6.3% in a series of
48 failed grafts
Faith, S. C., Durrani, A. F., & Jhanji, V. (2018). Cytomegalovirus keratitis.
Current Opinion in Ophthalmology, 29(4), 373–377
73. Conclusion
Viral keratitis is a major cause of ocular morbidity, adversely
affecting a patient’s quality of life, not only due to visual
handicap but also due to recurrent episodes
Early diagnosis and proper treatment, according to
prescribed regimen can contribute to good outcomes
Anti virals and steroids are mainstay of treatment
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