Various drugs used for viral infections of the eye

1. Anti-viral
Agents in
Ophthalmolog
y
Dr. B.A.Maithri
DNB Ophthalmology
M.N.Eye Hospital, Chennai

2. Introduction:
 Viruses – the ultimate expression of parasitism
Obligate intracellular organisms
 Difficult to target viruses without destroying host cells
 First anti-viral trial therapy – 1960’s against herpes

3. Virus vs Drugs

4. Classification
 Anti-Herpes : HSV & VZV: Idoxuridine, Acyclovir, Valacyclovir,
Famciclovir, Trifluridine, Vidarabine
CMV: Ganciclovir , Cidofovir, Foscarnet, Fomivirsen
 Anti–Influenza : Amantadine, Olsetamavir
 Anti-Retroviral : NRTI’s: Zidovudine
NNRTI’s: Nevirapine
Protease inhibitors: Indinavir
Entry/Fusion inhibitors : Enfuvirtide
 Non-selective : INF-alpha, Ribavirin , Adefovir

5.  1st Generation
1. Idoxuridine
2. Vidarabine
3. Trifluorothymidine
4. Cytarabine
 2nd Generation
1. Acyclovir
2. Bromo vinyl
deoxyuridine
3. Interferons
4. Famiclovir
5. Vabaciclovir
6. Foscarnet
7. Ganciclovir
8. Zidovudine
9. Sorvudine

6. 1st Generation

7. Idoxuridine:
Thymidine analog
MOA: Faulty dna – defective virus
Ind: Herpes simplex keratitis (superficial)
C/I: 1st few weeks of keratoplasty
Dosage: Topical only – 0.1% drops, 0.5% ointment
** not to continue after 3 weeks.

8. Idoxuridine
A/E : Blepharitis
Papillary conjunctivitis
Lid edema
Punctal occlusion
Photophobia
Ghost dendrites / scarring
Ptosis

9. Trifluridine:
Trifluorothymidine – pyramidine analog
MOA: inhibits Thymidine synthetase
Ind: DOC for primary & recurrent HSV keratitis (epi)
Deeper infections
IDU resistant cases
Thygeson’s superficial punctate keratitis
Dendritic HSV keratitis

10. Trifluridine
Dosage: 1% solution 6-9 t/d /2weeks
A/E: On prolonged use,
Irritation
Delayed epithelial healing
Conjunctival scarring
Stromal edema
Raised IOP

11. 2nd Generation

12. Acyclovir:
Guanosine analogue
MOA: Selective to virus-infected cells
active metabolite inhibits DNA polymerase
DNA formation stopped
DNA poly irreversibly inhibited.
no / little effect on host cells
broad spectrum
penetrates cornea well.

13. Acyclovir
Ind: primary HSV keratitis, dendritic ulcers
secondary keratitis in eczema
HSV iritis & blepharitis
Risk of recurrence > 2 times/yr
Post Keratoplasty
VZV and HZO
Acute retinal necrosis syndrome (ARN)
Immunosuppressed patients
cannot prevent post-herpetic neuralgia.

14. Acyclovir
Dosage: -3% ointment 5 t/d for 2 weeks – taper
-oral – 200mg upto 800mg 5 t/d for 10 days
400mg - prophylaxis
-given along with steroids in stromal keratitis
-Intra-Vitreal 5 mcg/0.1 ml weekly for ARN
-5% dermal cream for blepharitis
Resistance – Immunocompromised patients

15. Acyclovir
A/E: Well tolerated
Superficial punctate keratopathy
Burning sensation
Systemic : GI most common
Renal dysfunction
Neurological

16. Valacyclovir
Prodrug of acyclovir
similar spectrum
longer half-life, better bioavailability
orally 500mg/ 1000mg t.i.d
Famiciclovir
Prodrug of penciclovir
HZO – 500-700mg t.i.d for 7 days

17. Ganciclovir:
Synthetic guanine derivative
MOA: Prevents DNA elongation in CMV infected cells
Ind: CMV Retinitis in immunocompromised
To prevent CMV disease in transplant recipients
C/I: Hypersensitivity

18. Ganciclovir
Dosage: Oral – 250mg capsule
Intravenous- 5 mg/kg over 1 hour BD / 2-3 wks
Never given IM or S/C
IntraVitreal implant – 4.5 mg over 6-8months
A/E: Bone marrow toxicity
GI , Neurological
Intravitreal – conjunctival scar, uveitis, disc changes,
retinopathy, angle-closure glaucoma.

19. Foscarnet Sodium:
Organic pyrophosphate
MOA: selective inhibition of pyrophosphate in infected cells
Ind: CMV retinitis in AIDS
Acyclovir resistant HSV & VZV
Ganciclovir resistant CMV
Dosage: 24mg/ml infusion through central venous catheter
dilute only with NS or 5% dextrose
A/E: fever, nausea, anaemia, headache
acute renal failure, hypocalcemia

20. Fomivirsen Sodium:
Phosphorothioate oligonucleotide
MOA: inhibits protein synthesis of CMV by anti-sense
mechanism.
Ind: Resistant CMV retinitis
Dosage: 330 mcg intravitreal injection/ alt weeks.
A/E: Uveitis
Cataract
increased IOP
floaters
liver dysfunction

21. Cidofovir:
Newer drug, cytosine analog
MOA: inhibits CMV DNA polymerase
Ind: CMV retinitis
HSV, HZV
? Adenovirus
Dosage: 5mg/kg body wt IV infusion wkly for 2weeks.
A/E: renal toxicity
hepatic toxicity
hyperglycaemia
tachycardia

22. Thank you