Antibiotic and anti-inflammatory therapy for ocular diseases

1
Antibiotic and anti-inflammatory therapy for
ocular diseases

• Mario La Rosa

Dipartimento di Pediatria, UO di
Broncopneumologia, Allergologia e Fibrosi
Cistica, Università degli Studi di Catania
2
Antibiotic and anti-inflammatory therapy for
ocular diseases

• Introduction
• Antibiotic therapy
• Antibiotics for Specific Ophtalmic Conditions
• Steroidal anti-inflammatory drugs
• Non-steroidal anti-inflammatory drugs (NSAIDs)
• Conclusions

3
Antibiotic and anti-inflammatory therapy for
ocular diseases

• Introduction
• Antibiotic therapy
• Antibiotics for Specific Ophtalmic Conditions
• Steroidal anti-inflammatory drugs
• Non-steroidal anti-inflammatory drugs (NSAIDs)
• Conclusions

4
Ocular infections

• Eyes are organs with a high probability of
  contracting infections because of their
  anatomical position.
• Natural ocular mechanisms of defence are not
  always able to control infectous lesions.
• It is really important, for exemple, to diagnose
  corneal infections, because if they are not
  appropriately treated they can evolve in corneal
  opacities, with a deep decrease of sight.

5
Ocular infections

• Endophtalmithis need an urgent tratement in
  order to avoid the widespread of the infection in
  the closer tissues, that in serious cases can
  cause the loss of function of the ocular bulb

6
Ocular infections

• Allergic conjunctivities incidence is
  increasing and it affects a large amount of
  people, with some problems in its tratement. As a
  matter of fact therapy is based on the control of
  symptoms, without a definitely resolution of the
  disease.

7
Ophthalmic antibiotic therapy

• In the therapy of bacterial ocular diseases a
  large number of antibiotics acting locally alone
  or sistemically are being used.
• With the introduction of antibiotics in the
  1940s, effective tratement of blinding ocular
  infections finally became a reality. Since that
  time, to echo a popular slogan Weve come a
  long way.
• 
  
  
  

John P Witcher, West J Med 1994
8
Antibiotic and anti-inflammatory therapy for
ocular diseases

• Introduction
• Antibiotic therapy
• Antibiotics for Specific Ophtalmic Conditions
• Steroidal anti-inflammatory drugs
• Non-steroidal anti-inflammatory drugs (NSAIDs)
• Conclusions

9
Ophthalmic antibiotic therapy

• Antibiotics available for topical use in the eye
  are
• Chloramphenicol
• Fucidic acid
• Aminoglicosides
• Chlortetracyclines
• Fluoroquinolones
• Polymixin

Vale Janet Ophtal Physiol Opt 1998
10
Ophthalmic antibiotic therapy

• Cloramphenicol, fusidic acid, the
  aminoglicosides and chlortetracycline, show a
  quantitative biochemical selectivity. In
  differing ways they interact with bacterial
  ribosomes and inhibit the syntesis of bacterial
  proteins.

Vale Janet Ophtal Physiol Opt 1998
11
Ophthalmic antibiotic therapy

• Chlortetracycline shows a quantitative
  selectivity, which is in part biochemical,
  because of the differences between human and
  bacterial ribosomes, and in part distributional,
  as sensitive bacteria are able to accumulate
  higher concentrations of the drug, either by
  passive diffusion and by active transport.
• Vale
  Janet Ophtal Physiol Opt 1998

12
Ophthalmic antibiotic therapy

• The aminoglycocides framycetin, gentamicin and
  neomycin exert a rapid bactericidal effect which
  cannot be explained only trough inhibition of
  protein synthesis. As a matter of fact there is
  some evidence that these drugs cause a disruption
  of the cytoplasmatic membrane structure.
  
  

Vale Janet Ophtal Physiol Opt 1998
13
Ophthalmic antibiotic therapy

• The fluoroquinolones (ciprofloxacin, ofloxacin)
  are bactericidal through the inhibition of
  nucleic acid synthesis as a result of their
  inhibition of the enzyme DNA gyrase. The activity
  of this enzyme is necessary to initiate DNA and
  RNA synthesis.
• 
  
  

Vale Janet Ophtal Physiol Opt 1998

14
Ophthalmic antibiotic therapy

• The cationic detergent properties of the
  polymyxins allows them to interact with the
  phospholipids of the cell membrane. These drugs
  are then able to enter the membrane and disrupt
  its structure
  

Vale Janet Ophtal Physiol Opt 1998
15
Ophthalmic antibiotic therapy

• The Penicillins, which are bactericidal and
  qualitatively selective through their action in
  disrupting synthesis of bacterial cell walls, are
  not generally used topically because of
  widespread resistance and allergy problems.
  Selected compuonds, such as ticarcillin,
  carbenicillin, piperacillin are used by other
  routes for Pseudomonas infections.
  

Vale Janet Ophtal Physiol Opt 1998
16
Antibiotic and anti-inflammatory therapy for
ocular diseases

• Introduction
• Antibiotic therapy
• Antibiotics for Specific Ophtalmic Conditions
• Steroidal anti-inflammatory drugs
• Non-steroidal anti-inflammatory drugs (NSAIDs)
• Conclusions

17
Antibiotics for Specific Ophtalmic Conditions
Bacterial keratitis

• It is well known that the initial therapy for
  suspected bacterial keratitis should include
  broad-spectrum antibiotics, considering that this
  therapy should be altered if the corneal ulcers
  worsens and microbiological investigations prove
  that the responsable pathogen is resistant to the
  initial therapy.

Cameron N Ly MB BSClinical and Experimental
Ophthalmology 2006
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Ophthalmic antibiotic therapy in bacterial
keratitis

• With the increase of resistance among infective
  agents, it is important to know the antibiotic
  susceptibility of current ocular surface
  pathogens, in order to optimaze the initial
  therapy for patients with suspected bacterial
  keratitis.

Cameron N Ly MB BSClinical and Experimental
Ophthalmology 2006
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Ophthalmic antibiotic therapy in bacterial
keratitis

• Cameron N. and coll. performed a quantitative
  susceptibility testing to six antibiotics on all
  bacteria isolated from 112 patients who presented
  to the Sydney Eye hospital Emergency Department
  with presumed bacteria keratitis.
  

Cameron N Ly MB BSClinical and Experimental
Ophthalmology 2006
20
Ophthalmic antibiotic therapy in bacterial
keratitis

• Bacterial species isolated from corneal
  scrapings taken from 112 patients with suspected
  bacterial keratitis.

Cameron N Ly MB BSClinical and Experimental
Ophthalmology 2006
21
Ophthalmic antibiotic therapy in bacterial
keratitis

• Antibiotics used in the study. The initial
  topical antibiotic treatement is shown in the
  black bar and the number of successful cases
  shown in the shaded bar.

Cameron N Ly MB BSClinical and Experimental
Ophthalmology 2006
22
Ophthalmic antibiotic therapy in bacterial
keratitis

• The mentioned study showed that cephalosporins
  and aminoglycosides were complementary in their
  microbial cover.
• The Cephalosporin plus aminoglycoside combination
  therapy has proven an effective initial
  broad-spectrum treatement of bacterial keratitis
  in many other studies in London, Sweden and the
  USA.

Cameron N Ly MB BSClinical and Experimental
Ophthalmology 2006
23
Ophthalmic antibiotic therapy in bacterial
keratitis

• The use of fluoroquinolones has been shown to be
  an effective alternative for the usual
  cephalosporine and aminoglycoside combination
  therapy, as demonstrated in large prospective
  multicentre studies that supported the use of
  0,3 ciprofloxacin topical monotherapy and 0,3
  ofloxacin topical monotherapy.

Cameron N Ly MB BSClinical and Experimental
Ophthalmology 2006
24
Ophthalmic antibiotic therapy in bacterial
keratitis

• Ciprofloxacin is also one of a few antibiotics
  that enters the human eye after oral
  administration.

Cameron N Ly MB BSClinical and Experimental
Ophthalmology 2006
25
Ophthalmic antibiotic therapy in bacterial
keratitis

• Distribution of ciprofloxacin minimum inhibitory
  concentration (MIC). Fifty-one out of 53 isolates
  were likely to respond to ciprofloxacin (MIC lt/
  4,0)
• 
  Cameron N Ly MB BSClinical and Experimental
  Ophthalmology 2006

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Antibiotics for Specific Ophtalmic Conditions

• 
  Conjunctivitis
• Most cases of conjunctivitis have a viral
  etiology, with prominent symptoms being itchy,
  watery, red eyes with lid and conjunctival edema.
  In this case eyedrop antibiotics are useful to
  prevent a secondary bacterial infection.
• Good choises include
• Polytrim
• Tobramycin
  

Richmond Eye Associates Ophtalmology Update Jul
2001
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Antibiotics for Specific Ophtalmic Conditions

• Conjunctivitis

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Antibiotics for Specific Ophtalmic Conditions

• 
  Conjunctivitis
• Bacterial conjunctivitis is characterized by a
  copious purulent discharge.
• Good antibiotic choises include
• Polytrim
• Ocuflox
• Gentamycin
• Tobramycin
• Neosporin

Richmond Eye Associates Ophtalmology Update Jul
2001
29
Antibiotics for Specific Ophtalmic Conditions

• Conjunctivitis
• Chlamydia Trachomatis is a cause of chronic
  conjunctivitis and appropriate systemic
  treatement is indicated along with Erythromycin
  ophthalmic ointment.

Richmond Eye Associates Ophtalmology Update Jul
2001
30
Antibiotics for Specific Ophtalmic Conditions

• Prophylaxis of corneal abrasions
• Antibiotics eyedrops or ointments should be used
  during the healing period of corneal abrasions to
  prevent corneal ulcer.
• Good antibiotic choices include
• Gentamicin, Tobramycin, Polytrim
• Cipro, Ocuflox, Quixin (if there are stronger
  risk factors for infection due to the nature of
  the injury)
• Erythromycin, Bacitracin (for particularly large
  corneal abrasions)

Richmond Eye Associates Ophtalmology Update Jul
2001
31
Antibiotics for Specific Ophtalmic Conditions

• Blepharitis
• For significant flare-ups of the condition,
  antibiotic oinments applied at bedtime such as
  Erytromycin, Bacitracin or Tobramycin can be
  useful. Yet short courses fo steroid/antibiotic
  combination oinments such as Maxitrol, Dexacidin
  and Tobradex may give more rapid relief.
  

Richmond Eye Associates Ophtalmology Update Jul
2001
32
Antibiotics for Specific Ophtalmic Conditions

• Blepharitis

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Antibiotics for Specific Ophtalmic Conditions

• Endophthalmitis
  

John P Witcher, West J Med 1994
34
Antibiotics for Specific Ophtalmic Conditions

• Endophthalmitis

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Antibiotics in ocular tuberculosis

• The most common manifestation of the ocular
  involvment in tuberculosis is uveitis, usually
  presenting as a chronic anterior uveitis,
  panuveitis or as a choroiditis.
• In the posterior ocular pole it is possible to
  find choroidal tubercles, which appear yellow,
  becoming more pigmented as the time passes.

C. Micheal Samson, M.C. The Ocular Immunology
and Uveitis Foundation 1999
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Antibiotics in ocular tuberculosis

• Fundus potographs and corresponding fluorescein
  angiogram of presumed choroidal tubercle. The
  patient was strongly PPD reacting and was treated
  with anti-tuberculous medications.
• Photos courtesy of Joseph Walsh , M.D., Chairman
  of Ophthalmology at the New York Eye and Ear
  Infirmary.

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Antibiotics in ocular tuberculosis

• Fundus photo and corresponding fluorescein
  angiogram of the same patient, after six months
  of treatement with anti-tuberculous medications.
• Photos courtesy of Joseph Walsh , M.D., Chairman
  of Ophthalmology at the New York Eye and Ear
  Infirmary.

38
Antibiotic and anti-inflammatory therapy for
ocular diseases

• Introduction
• Antibiotic therapy
• Antibiotics for Specific Ophtalmic Conditions
• Steroidal anti-inflammatory drugs
• Non-steroidal anti-inflammatory drugs (NSAIDs)
• Conclusions

39
Ophthalmic anti-inflammatory therapy

• Anti-inflammatories drugs used in ophthalmology
  can be divided in two groups
• Topic and injectable steroidal antiinflammatories
• Non steroidal antiinflammatories

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Steroidal anti-inflammatory drugs

• These kind of drugs are lack of specificity, and
  they have been used for several years as
  treatement of inflammation and immunological
  ophthalmic diseases.

Genevieuve N Clinical and Experimental Optometry
2006
41
Steroidal anti-inflammatory drugs mechanisms of
action

• Their antiinflammatory and immunosuppressive
  action can be related to the following actions
• Inhibition of lymphocites proliferation, above
  all lymphocytes T, with a decrease of the
  cell-mediated immunity
• Suppression of lymphokines action, of macrophage
  migration and of the production of some growth
  factors

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Steroidal anti-inflammatory drugs mechanisms of
action

• Inhibition of the degranulation of neutrophil
  granulocytes, macrophages, mastcells and basophil
  granulocytes.
• Decrease of vascular permeability
• Decrease of Prostaglandines production as
  consequence of the suppression of arachidonic
  acid synthesis.
  

Genevieuve N Clinical and Experimental Optometry
2006
43
Steroidal anti-inflammatory drugs
Genevieuve N Clinical and Experimental Optometry
2006
44
Steroidal anti-inflammatory drugs

• Prednisolone
• Studies shows that Prednisolone has the greatest
  anti-inflammatory efficacy of all topical
  ophthalmic steroids.
• Prednisolone acetate 1 is the most effective of
  the topical ophthalmic steroids for the
  treatement of uveitis and corneal
  inflammations.it is well suited for treating
  severe forms of ocular inflammation such as
  episcleritis, iritis, chemical/termal burns of
  the cornea.
• 
  

Reveiw of optamometry June 2006
45
Steroidal anti-inflammatory drugs

• Dexamethasone
• In its approved concentration, Dexamethasone is
  less clinically effective than prednisolone and
  has a greater tendency to raise intraocular
  pressure, making it a drug of second choise.
• 
  

Reveiw of optamometry June 2006
46
Steroidal anti-inflammatory drugs

• Fluorometholones
• They possesses good to excellent
  anti-inflammatory properties , while having a
  diminished propensity to cause secondary IOP
  increase.
• There are two formulations of fluorometholone,
  the alchool and the acetate.
• 
  

Reveiw of optamometry June 2006
47
Steroidal anti-inflammatory drugs

• Fluorometholone alchool
• It is used very commonly to treat a host of mild
  to moderate ocular scurface inflammatory
  conditions, requiring long-term (beypnd three to
  four week) therapy such as low-grade chronic
  iridocyclitis and some cases of ocular allergy.
• Its usefulness in chronic care lies in its
  reduced tendency to cause secondary IOP increase.
• 
  

Reveiw of optamometry June 2006
48
Steroidal anti-inflammatory drugs

• Fluorometholone acetate
• This is the more clinically active form of the
  more familiar FML. The acetate formulation
  confers to fluorometholone greater clinical
  efficacy.
• The indications for this product are essentially
  the sae for the other corticosteroids.
• 
  

Reveiw of optamometry June 2006
49
Steroidal anti-inflammatory drugs

• Rimexolone
• It is a potent, relatively safe preparation, and
  it is close to, but not as effcacious as 1
  prednisolone acetate yet its decreased
  propensity to raise intraocular pressure is very
  similar to that of the fluorometholones.
• 
  

Reveiw of optamometry June 2006
50
Antibiotic and anti-inflammatory therapy for
ocular diseases

• Introduction
• Antibiotic therapy
• Antibiotics for Specific Ophtalmic Conditions
• Steroidal anti-inflammatory drugs
• Non-steroidal anti-inflammatory drugs (NSAIDs)
• Conclusions

51
Non-steroidal anti-inflammatory drugs (NSAIDs)

• They are inhibitors of prostaglandines
  synthesis with an anti-inflammatoey and analgesic
  activity.
• The advantage of using them than steroidal
  agents is related to the fact that they do not
  induce a decrease of immunosystem activity.
• Moreover they do not interact with the ocular
  hydrodynamic.

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Ophthalmic non-steroidal anti-inflammatory drugs

• Most current NSAIDs inhibit both forms of the
  cyclo-oxygenase (COX) enzyme.
• Inhibition of the synthetic pathway from
  arachidonic acid to the prostaglandines may
  result in increased production of leukotrienes
  which are also inflammatory.
• This may have serious consequances for some
  patients, e.g asthmatics, as the leukotrienes
  cause bronchoconstriction.
• 
  

Genevieuve N Clinical and Experimental Optometry
2006
53
Ophthalmic non-steroidal anti-inflammatory drugs

• Currently they are used in intra- and/or
  post-operative situations to reduce miosis during
  surgery and inflammation following cataract
  surgery, laser trabeculoplasty and PRK.
• They are also used in the prevention and
  treatment of cystoid macular oedema and for the
  treatment of allergic conjunctivitis.

Vale J Ophthalm Physiol Opt 1998
54
Ophthalmic non-steroidal anti-inflammatory drugs

• Other therapeutics indications of NSAIDs in
  ocular diseases are
• Inflammations of the anterior segment of the eye,
  which do not recognize a viral o bacterial
  etiology, such as corneal and conjunctical
  edemas, scleritis.
• Inflammatory reactions due to traumas
• Cornela neovascularization due to the use of
  contact lenses and its following inflammation.
• 
  

Vale J Ophthalm Physiol Opt 1998
55
Ophthalmic non-steroidal anti-inflammatory drugs

• The topic NSAIDs actually in commerce all over
  the Europe are
• Diclofenac sodico
• Flubiprofene sodico
• Ketorolac trometamina
• Piroxicam
• Indometacina
• Suprofene

Genevieuve N Clinical and Experimental Optometry
2006
56
Antibiotic and anti-inflammatory therapy for
ocular diseases

• Introduction
• Antibiotic therapy
• Antibiotics for Specific Ophtalmic Conditions
• Steroidal anti-inflammatory drugs
• Non-steroidal anti-inflammatory drugs (NSAIDs)
• Conclusions

57
Conclusions

• Infections of the eye can rapidly damage
  important functional structures and lead to
  permanent vision loss or blindness.
• Broad-spectrum antibiotics should be administered
  to the appropriate site of infection as soon as a
  diagnosis is made.
• Topical drops are preferred for corneal and
  conjunctival infections.
• Intravitreal antibiotics, and possibly
  subconjunctival and parenteral antibiotics, are
  preferred for endophthalmitis.
• Parenteral antibiotics are recommended for
  infection in deep adnexal structures.

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Conclusions

• Is important to make a clinical diagnosis before
  treatment and of following the clinical course of
  patients carefully during treatment
• Because of the potential for side effects,
  treatment must be individualized and regular
  monitoring performed.
• With careful use of immunosuppressive drugs for
  treatment of ocular inflammatory disorders, many
  patients will benefit from them either with
  better control of the ocular inflammation or with
  a decrease in corticosteroid side effects.

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