1. -Ajay Kumar Singh
-Shashi Sharma
•Department of Ophthalmology
•King George‘s Medical University, Lucknow (INDIA)

2.  ANTIMICROBIALS
 LOCAL ANAESTHETICS
 ANTINEOPLASTIC DRUGS
 ANTIOXIDANTS
 ANTI VEGF

3. ANTIMICROBIAL AGENTS
 Synthetic as well as naturally obtained drugs that attenuate microorganisms.
 CLASSIFICATION:
 On the basis of type of organism, they inhibit-
Antibacterial- Penicillins, Aminoglycosides, Fluoroquinolones etc.
Antifungal- Amphotericin B, Fluconazole etc.
Antiviral- Acyclovir, Zidovudine etc.
Antiprotozoal- Metronidazole
Antihelminthic- Albendazole, Niclosamide etc.

4.  On the basis of mechanism of action:
Inhibit cell wall synthesis- Penicillins, Cephalosporins
Cause leakage from cell membrane- Amphotericin B
Inhibit protein synthesis- Tetracyclines, Chloramphenicol
Cause misresding of m-RNA code- Aminoglycosides
Inhibit DNA gyrase- Fluoroquinolones
Interfere with DNA function- Metronidazole, Rifampicin
Interfere with DNA synthesis- Acyclovir, Zidovudin

5.  On the basis of type of action
Primarily bacteriostatic Primarily bactericidal
Sulfonamides Penicillins
Tetracyclines Cephalosporins
Chloramphenicol Aminoglycosides
Fluoroquinolones
Vancomycin

6. Antibacterials
 Used locally (topically and
subconjunctivally) in prophylaxis (pre and
postoperatively) and treatment of ocular
bacterial infections.
 Used systemically (orally and
intravenously) for the treatment of
preseptal/orbital cellulitis
e.g. amoxycillin with clavulanate, ,
cephalosporin, vancomycin
 Can be injected intravitreally for the
treatment of endophthalmitis

7. ANTIBACTERIAL AGENTS
PENICILLINS:
 Bactericidal
 Short half-life
 Excreted mainly via kidney; a small fraction via biliary tract
 Act by interfering with cell wall synthesis
 Most have narrow spectrum, mainly against Gram-positive organisms
 Have synergistic action with aminoglycosides

8.  3 major groups:
 Penicillins effective against cocci and Gram-positive bacilli
 Eg. Benzyl penicillin (non acid stable) and penicillin V (acid stable)
 Penicillinase resistant penicillins
 Eg. Cloxacillin and flucloxacillin
 Extended spectrum penicillins
 Aminopenicillins: Ampicillin, Amoxycillin
 Carboxypenicillins: Ticarcillin, Carbenicillin
 Ureidopenicillins: Piperacillin, Mezlocillin

9.  β- LACTAMASE INHIBITORS:
Clavulanic acid:
 Obtained from Streptomyces clavuligerus
 Tissue distribution and elimination matches Amoxicillin
 Combination- COAMOXYCLAV (Amoxycillin 250/500 mg + clavulanic acid 125 mg)
Sulbactum:
 Less potent than clavulanic acid
 Oral absorption inconsistent: given parenterally
Tazobactum:
 Pharmacokinetics matches Piperacillin (combination- TAZOMAC : Piperacillin 4g + tazobactum 0.5g)

10. Here comes your footer 
DRUGS SPECTRUM DOSE
Penicillin
derivatives
Penicillin Gram-positive organisms, Spirochetes SYSTEMIC- 4-30 million U in 24 divided doses 4-6
hourly
TOPICAL- 0.1 million U/mL (Fortified drops)
Cloxacillin Gram-positive organisms, also penicillinase
producing
SYSTEMIC-50-100mg/kg/day oral/i.v. 6 hourly
Ampicillin Gram-positive organisms, H. influenzae, E. coli,
Proteus, Salmonella, Shigella
SYSTEMIC-50-100mg/kg/day oral/i.v. 6 hourly
TOPICAL- 10 mg/mL (Fortified drops)
INTRAVITREAL- 500 mg/mL
Amoxycillin Gram-positive organisms SYSTEMIC-25-50mg/kg/day oral 8 hourly

11.  CEPHALOSPORINS:
Structure and mode of action similar to penicillins (bactericidal)
Relatively resistant to staphylococcal penicillinase
Patients allergic to penicillin may develop allergy
Intraocular penetration not very good

12. DRUGS SPECTRUM DOSE
Cephalosporins
1st
Generation
Cephalexin Gram-positive organisms, penicillinase producing
staphylococci, C.diphtheriae, Clostridia, Actinomyces,
E. coli, Klebsiella, Shigella, Salmonella, Proteus, H.
influenzae
25-50 mg/kg/day oral 6 hourly
Cephazolin Gram-positive organisms, E. coli, Proteus, H.
influenzae
25-50 mg/kg/day i.m./i.v. 8 hourly
TOPICAL-50 mg/mL (Fortified drops)
INTRAVITREAL- 2.25 mg in 0.1 mL
2nd
Generation
Cefamandole Gram-positive organisms, E. coli, Proteus, H.
influenzae
1 gram 4 hourly i.v.
TOPICAL- 50 gram/mL (Fortified drops)
Cafaclor Gram-positive organisms, E. coli, Proteus, H.
influenzae
25-50 mg/kg/day oral 8 hourly
Cefuroxime Gram-positive and negative organisms, penicillinase-
producing N.gonorrhoeae, ampicillin-resistant H.
influenzae
30-100 mg/kg/day i.m./i.v. 8-12 hourly

13. DRUGS SPECTRUM DOSE
3rd
Generation
Cefotaxim Aerobic Gram-negative organisms 100-150 mg/kg/day i.m./i.v. 8-12
hourly
TOPICAL- 50 mg/mL (Fortified drops)
Ceftriaxone Aerobic Gram-negative organisms 80-150 mg/kg/day i.v. 8-12 hourly
Cefoperazone Gram-positive organisms, Pseudomonas, Salmonella,
Bacteroides fragilis
50-200 mg/kg/day i.m. 8-12 hourly
Ceftazidime Aerobic Gram-negative organisms, Pseudomonas 50-100 mg/kg/day i.v. 8-12 hourly
INTRAVITREAL- 2.25 mg in 0.1 mL

14.  AMINOGLYCOSIDES:
Bactericidal
Broad spectrum of activity against Gram-positive and Gram-negative
organisms
Renal and vestibular toxicity
Interfere with neuromuscular conduction- may cause paralysis in
Myasthenia gravis patients
Intravitreal injections may cause retinotoxicity

15. DRUGS SPECTRUM DOSE
Aminoglycosides
Gentamicin Aerobic Gram-negative organisms,
Pseudomonas, Proteus, E.coli, Klebsiella
SYSTEMIC- 4-8 mg/kg.day i.m./i.v. 8 hourly
TOPICAL- 0.3% drops/ointment
INTRAVITREAL- 200-400 μg in 0.1 mL
Amikacin Aerobic Gram-negative organisms,
gentamicin-resistant organisms
SYSTEMIC- 15-20 mg/kg.day i.m./i.v. 8 hourly
TOPICAL- 0.3% drops
INTRAVITREAL- 400 μg in 0.1 mL
Tobramycin Aerobic Gram-negative organisms,
Proteus, Pseudomonas
SYSTEMIC- 6-7.5 mg/kg/day i.m./i.v. 8-12 hourly
TOPICAL- 0.3% drops/ointment
INTRAVITRAL- 150-200 μg/mL
Neomycin most Gram-negative bacilli and some
Gram-positive cocci
SYSTEMIC- 4-12 gram/day 6 hourly
TOPICAL- 0.17% drops, 5 mg/gram ointment
Framycetin Activity similar to neomycin TOPICAL- 0.5% drops

16.  TETRACYCLINES:
Broad spectrum antibiotics with bacteriostatic action against both Gram-
positive and Gram-negative organisms as well as some fungi, rickettsiae and
chlamydiae.
Get deposited in growing bones- not to be used in children and pregnant or
lactating mothers
 MACROLIDES:
Bacteriostatic agents with narrow spectrum against Gram-positive
organisms, Chlamydia and Toxoplasma gondii.

17. DRUGS SPECTRUM DOSE
Tetracycline and its
derivative
Tetracyclin Gram-positive and negative organisms SYSTEMIC-50 mg/kg/day oral 6 hourly
TOPICAL- 1% drops/ointment
Doxycyclin Gram-positive and negative organisms,
spirochaetes, rickettsiae, chlamydiae,
Mycoplasma, Actinomyces, Entamoeba
histolytica
SYSTEMIC- 1.5-2 mg/kg/day oral 12-24 hourly
Macrolides
Erythromycin Gram-positive cocci, H.influenzae,
E.coli, Mycoplasma, Salmonella,
Chlamydia
SYSTEMIC- 1-4 gram/day oral/i.v. 6 hourly
TOPICAL- 0.5% ointment
INTRAVITREAL- 500 μg/mL
Azithromycin Gram-positive organisms, Chlamydia,
Toxoplasma gondii
SYSTEMIC-20-30 mg/kg oral single dose
TOPICAL- 1% drops
Vancomycin Gram-positive organisms,
staphylococci, MRSA, enterococci,
Streptococcus viridans, Clostridium
SYSTEMIC- 2 gram/day 6-12 hourly
TOPICAL- 50 mg/mL (Fortified drops)
INTRAVITREAL- 1 mg in 0.1 mL
Combination drugs
Co-trimoxazole (400 mg
sulphamethoxazole + 80 mg
trimethoprim)
Gram-positive and negative organisms SYSTEMIC-6 mg of trimethoprim
equivalent/kg/day oral 12 hourly

18.  GLYCOPEPTIDES:
Very effective against nearly all Gram-positive as well as against methicillin-
resistant Staphylococcus aureus and Staphylococcus epidermidis.
toxic if used topically or subconjunctivally
VANCOMYCIN:
 High systemic toxicity
 Nephro and ototoxic
 Used intravitreally/parenterally for treatment of endophthalmitis

19.  FLUOROQUINOLONES:
Derivatives of nalidixic acid
Broad spectrum agents
 1st
generation
• active mainly against Gram-negative organisms
• Eg. Norfloxacin, Ciprofloxacin, Ofloxacin, Pefloxacin
 2nd
generation
• also active against Gram-positive and anaerobe organisms
• Eg. Levofloxacin, Lomefloxacin, Gatifloxacin, Moxifloxacin
Get deposited in growing cartilage- not recommended in children

20. DRUGS SPECTRUM SYSTEMIC DOSE TOPICAL/ INTRAVITREAL
DOSE
Fluoroquinolones
Ciprofloxacin Actinomyces, Nocardia
spp., Toxoplasma spp.
Aerobic Gram-negative
organisms
15-20 mg/kg/day oral 12
hourly
7-10 mg/kg/day i.v. 12 hourly
TOPICAL- 0.3% drops/ointment
INTRAVITREAL- 100 μg in 0.1 mL
Norfloxacin Aerobic Gram-negative
organisms
10 mg/kg/day oral12 hourly TOPICAL- 0.3% drops/ointment
INTRAVITREAL- 100 μg in 0.1 mL
Ofloxacin Gram-positive and
negative organisms
200-400 mg oral 12 hourly TOPICAL- 0.3% drops/ointment
INTRAVITREAL- 100 μg in 0.1 mL
Levofloxacin Gram-positive and
negative organisms
250-750 mg oral/i.v. 24 hourly TOPICAL- 0.5% drops
INTRAVITREAL- 150 μg in 0.1 mL
Gatifloxacin Gram-positive and
negative organisms
200-400 mg oral 24 hourly TOPICAL- 0.3%, 0.5% drops,
0.3% ointment
Moxifloxacin Gram-positive and
negative organisms
200-400 mg oral/i.v. 24 hourly TOPICAL- 0.5% drops/ointment

21.  CHLORAMPHENICOL:
Bacteriostatic agent
Active against bacteria, spirochaetes, rickettsiae, chlamydiae and
mycoplasmas
Widest spectrum for superficial ocular infections
Toxic to the corneal epithelium
May lead to blood dyscrasias

22.  SULPHONAMIDES:
Bactriostatic agents
Used against Gram-positive bacteria and Chlamydia.
Eg. Topical 10-30% sulphacetamide- Trachoma

23. ANTI FUNGALS
Classified on the basis of molecular structure
Polyenes Imidazole Triazoles
Amphotericin B Natamycin Ketoconazole
Fluconazole Itraconazole Voriconazole

24. Polyenes
 First effective antifungal used
 Bind preferentially to ergosterol in fungal plasma membrane, thereby altering membrane permeability
and disruption of fungal cells
 Has poor corneal penetration
 Used effectively against variety of filamentous fungi Aspergillus, Candida, Histoplasma
 Local hypersensitivity and corneal epithelial toxicity may occur
 Prolong use may cause renal, bone marrow or CNS toxicity

25. AMPHOTERICIN B NATAMYCIN
Produced from Streptomycetes nodosus Streptomyces natalenses
Dosage •TOPICAL: 0.075-0.3% drops/hourly
•SUBCONUJNCTIVAL: 0.8-1 mg
•INTRAVITREAL: 500 μg in 0.1 mL
•SYSTEMIC: 1mg/kg in 5% dextrose 4 hourly i.v.
*Pretreat with 25mg hydrocortisone
TOPICAL: 5% ophthalmic suspension/hourly
interval followed by gradual tapering
Topical suspension should be shaken well
before use
Indications Aspergillus, Candida, Cryptococcus and
mucormycosis
Candida, Histoplasma and Actinomycetes
Considered superior but has to be reconstituted
and has low shelf life
DOC
Easily available in solution form
Trade names Amphocin, Fungizone Natamet, Nataone, NataAid

26. Clotrimazole
 Chlorinated imidazole derivative
 Broad antifungal activity more active in treatment of aspergillus infections
 DOSAGE:
 1% topical ophthalmic drops and ointment
 Topical drops are instilled hourly followed by gradual tapering
 Ointment is applied 4 times a day
 Adverse reactions include ocular irritation and punctate keratopathy

27. Fluconazole
 Most effective against yeast species Candida and Cryptococcus
 DOSAGE:
 0.3% solution
 Every 4 hour interval with gradual tapering
 Has faster and deeper penetration
 Highly effective in fungal keratitis with deep abscess
 Adverse reactions are minimal irritation and transient burning of the eyes

28. Itraconazole
 Shares a similar pharmacokinetic profile with fluconazole
 Used in Aspergillius infections, has moderate effects against Candida
 DOSAGE:
 1% ophthalmic solution
 8 times a day is the recommended dosage

29. Voriconazole
 Indicated for use in the treatment of fungal keratitis caused by
Aspergillus spp., Fusarium spp.,Candida spp. and Scedosporium
apiospermum
 PREPARATION:
Lyophilized form
 enhances drug stability and solubility
30 mg powder reconstituted with 3 mL to get 10 mg/mL
(1% solution)
 ADVERSE EFFECTS:
it may cause serious hepatic reactions

30. ANTI VIRAL DRUGS
 Anti viral drugs are activated to triphosphate by viral and cellular thymidine
kinases (TK)
 This active metabolite then inhibits DNA/RNA replication by competitive
inhibition and direct incorporation into viral DNA resulting in chain termination
 Oral Acyclovir- 800 mg, 5 times/day
 ADVERSE EFFECTS:
Blurring of vision, dizziness, drowsiness, tremors, severe allergic reactions, hematuria
 Acyclovir and Ganciclyovir ointment are available for topical use

31. ACYCLOVIR (3%) GANCICYCLOVIR (0.15%)
Indications • Primary HSV keratitis, dendritic ulcers
• Herpes zoster and varicella infections
• Acute retinal necrosis syndrome
Adverse effects • Vision blurred,irritation,Punctate keratitis
• Conjunctival hyperemia
• Erythema of eyelid, SPK
• Dry eye, Foreign body sensation
Dosage 5 times a day, followed by tapering
Acyclovir vs Gancicyclovir Ganciclovir ophthalmic gel 0.15% is a new dosage form recently approved by
the FDA for the treatment of acute herpetic keratitis (dendritic ulcers).
Better penetration than acyclovir with lesser side effects
Trade name ACIVIR OINTMENT® VIRSON GEL®

32. LOCAL ANAESTHETICS
 Topical: (drops/jelly)
E.g. Proparacaine 0.5%, Lignocaine 2%
Uses: applanation tonometry, goniscopy,removal of corneal foreign bodies,
removal of sutures, examination of patients, cataract surgery
Adverse effects: toxic to corneal epithelium, rarely allergic reactions

33.  Orbital infiltration:
 Peribulbar
 Retrobulbar
cause anesthesia and akinesia for intraocular surgery
e.g. Lidocaine 2%, Bupivacaine 0.25%-0.5%

34. ANTINEOPLASTIC AGENTS
 These are used in chemotherapy of ocular tumours
 some are used to decrease the fibroblastic response in ocular surgeries
 CLASSIFICATION:
Alkylating agents:
 eg. Carboplatin
Antimetabolites:
 eg. Methotrexate, Azathioprine, 5- Fluorouracil
Natural products:
 Plant products: eg. Vincristine, Etoposide
 Microorganism product: eg. Mitomycin C

35. DRUG GROUP MECHANISM USED IN DOSES
Carboplatin Alkylating agent-
Platinum co-
ordination complex
Alkylation of nucleic
acid resulting in cross
linking/ abnormal base
pairing of DNA strands
Ocular tumours 560 mg/m2 BSA (body
surface area) i.v.
Vincristine Vinca alkaloids Arrest the cell cycle in
mitotic phase by
disrupting mitotic
spindle
Ocular tumours 1.5 mg/m2 BSA i.v.
Etoposide Epipodophyllotoxins Arrests cells in G2
phase and inhibits DNA
topoisomerase II
Ocular tumours 150 mg/m2 BSA i.v.
5-Fluorouracil Antimetabolite-
Pyrimidine
antagonist
Iinhibition of
pyrimidine synthesis
To prevent excessive
scarring in postoperative
period (eg. pterygium
surgery, trabeculectomy)
25 mg/mL topical
Mitomycin C Antibiotic alkylating
agent
cross linking of DNA as
well as an inhibition of
RNA and protein
synthesis
After pterygium and
glaucoma surgery
(trabeculectomy) to reduce
scarring and recurrence
Ocular surface neoplasias
0.2-0.5 mg/mL (0.02%-
0.05%) solution topical

36. ANTIOXIDANTS
 Oxidative damage plays a major role in development of many ophthalmic
conditions; viz.
Senile cataract, age related macular degenerations (ARMD), diabetic retinopathy etc.
 Mechanism of oxidative damage:
Free radicals and reactive oxygen species are main culprits
Attack proteins (enzymes), neurotransmitters, nucleic acids, phospholipids, retinal
pigment epithelium, lens tissue
 Antioxidants react rapidly with free radicals and reactive oxygen species
 Act as scavengers for free radicals

37.  INDICATIONS:
Senile cataract
Age related macular degeneration
Diabetic retinopathy
Retinopathy of prematurity
Ischemic ophthalmopathy
Corneal inflammatory disorders
Open angle glaucoma

38.  PREPARATIONS:
Various standardised antioxidant combinations, available in form of
capsules; eg.
 i) Zn 30mg, Cu 1.5mg, Se 60 μg, Mn 5mg, vit.A 6000 IU, vit.B2 20 mg, vit.C
200 mg, vit.E 60 IU
 ii) mixed carotenoids, i.e. α-carotene, β-carotene, cryptoxanthin, leutin,
zeaxanthin

39.  Major role of various antioxidant elements:
 Zinc: integral part of two endogenous antioxidant enzymes viz. catalase and
superoxide dismutase
 Copper: cofactor for superoxide dismutase
 Selenium: cofactor for glutathione peroxidase
 Vitamin C: directly reacts with and scavenges free radicals; major function is
protection of lens from oxidative damage
 Vitamin E: intercalates into cell membrane and protects cellular constituents
against free radicals

40.  Carotenoids: major action is to suppress lipid peroxidation (responsible for
generation of free radicals)
 Lutein and zeaxanthin: only carotenoids found in the retina and lens of the eye.
They help reduce risk of developing age-related cataracts and macular
degeneration
 Astaxanthin: The most powerful of the carotenoids, by far. Astaxanthin can
penetrate into every part of the cell

41.  Newer Drug:
 PENTOXIFYLLIN: (TRENTAL®)
 Xanthine derivative
 Major action: improves blood flow in microcirculation
 Mechanism:
competitive phosphodiesterase inhibitor
 raises intracellular cAMP
 inhibits TNF-alpha and leukotriene synthesis reduces inflammation
 USES:
Hemorrhagic and ischemic retinal damage,
arteriosclerotic chorioretinal dystrophy,
ischemic optic nerve damage in glaucoma

42. ANTI VEGF
 Anti Vascular Endothelial Growth factors
 VEGF stimulates both angiogenesis and increased vascular permeability
 Major angiogenic factor implicated in the pathogenesis of neovascular and
exudative eye diseases
 Anti VEGFs inhibit VEGF and thus evolution of the disease

44. Wet ARMD Diabetic retinopathy BRVO
ROLE OF ANTI VEGF:

45. Retinopathy of Prematurity
Eales’ Disease
Refractory post surgical CME
Central serous chorioretinopathy
Trabeculectomy (to modulate wound healing)
Coat’s disease

46.  INDICATIONS IN ANTERIOR SEGMENT:
Neovascular glaucoma
Iris neovascularization
Before keratoplasty to reduce corneal vascularization

47. PEGAPTANIB RANIBIZUMAB BEVACIZUMAB
TRADE NAME Macugen® Lucentis ® Avastin®
COMPOUND Aptamer Antibody fragment
RhuFab
Full humanized mouse
Monoclonal antibody
VEGF BINDING
PROPERTY
VEGF-A 165
Selective
VEGF-A all forms VEGF-A all forms
DOSE 0.3 mg in 90 μl 0.5mg in 0.05 mL 1.25 mg in 0.05 mL
DURATION OF
ACTION
1/6 weeks 1/month 1/3 months
COST Rs 47,000/syringe Rs 56,000/vial Rs 37,000/vial
ADVANTAGES Low immunogenicity
Selective action
Longer acting than
pegaptanib
cost effective
Long acting
DISADVANTAGES cost CVS risks HTN, CVS risks
Rebound macular edema

48. FUTURE DRUGS…

49. TOPICAL IMMUNE THERAPY
 Relatively new concept
 To treat iatrogenic inflammation following any type of intraocular surgery
 To make up the decreased levels of ocular immunoglobulins vital for ocular
defence system against external infections

50.  WHY REQUIRED:
In immediate postoperative period (≈7 days) there is significant decrease in
globulin levels of tears
There is increase in tear secretion following surgeries, resulting in dilution of
immunoglobulins
There is physical breach in the continuity of ocular tissue, predisposing to
infections

51.  DOSAGE:
Available as:
 Topical solution (ASPAC)
 0.1% each of IgG and IgA and 0.05% of IgM
1-2 drops 3-4 times/day for 7-14 days
 ADVERSE EFFECTS:
Only occassionaly- transient burning sensation, stinging, conjunctival
injection, hypersensitivity reactions (rarely)