Farmaci in Oculistica1 - LA Rosa

7/30/2019 Farmaci in Oculistica1 - LA Rosa

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Antibiotic and anti-inflammatory

therapy for ocular diseases

Mario La Rosa

Dipartimento di Pediatria, UO di Broncopneumologia,

Allergologia e Fibrosi Cistica, Universit degli Studi di

Catania


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Introduction

Antibiotic therapyAntibiotics for Specific Ophtalmic Conditions

Steroidal anti-inflammatory drugs

Non-steroidal anti-inflammatory drugs(NSAIDs)

Conclusions




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Introduction

Antibiotic therapyAntibiotics for Specific Ophtalmic Conditions


Non-steroidal anti-inflammatory drugs(NSAIDs)

Conclusions




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Ocular infections

Eyes are organs with a high probability ofcontracting infections because of their anatomicalposition.

Natural ocular mechanisms of defence are notalways able to control infectous lesions.

It is really important, for exemple, to diagnosecorneal infections, because if they are notappropriately treated they can evolve in cornealopacities, with a deep decrease of sight.


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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


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Ocular infections

Allergic conjunctivities incidence is

increasing and it affects a large amount ofpeople, 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.


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Ophthalmic antibiotic therapy

In the therapy of bacterial ocular diseases alarge 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 echoa popular slogan: Weve come a long way.

John P Witcher, West J Med 1994


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Introduction

Antibiotic therapy

Antibiotics for Specific Ophtalmic Conditions


Non-steroidal anti-inflammatory drugs

(NSAIDs)

Conclusions




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Antibiotics available for topical use in the eye are:

- Chloramphenicol

- Fucidic acid- Aminoglicosides

- Chlortetracyclines

- Fluoroquinolones

- Polymixin

Vale Janet; Ophtal Physiol Opt 1998


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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.



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Chlortetracycline shows a quantitative

selectivity, which is in part biochemical,

because of the differences betweenhuman and bacterial ribosomes, and in

part distributional, as sensitive bacteria are

able to accumulate higher concentrationsof the drug, either by passive diffusion and

by active transport.



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The aminoglycocides framycetin,gentamicin and neomycin exert a rapidbactericidal effect which cannot be

explained only trough inhibition of proteinsynthesis. As a matter of fact there issome evidence that these drugs cause adisruption of the cytoplasmatic membrane

structure.



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The fluoroquinolones (ciprofloxacin, ofloxacin)are bactericidal through the inhibition of nucleicacid synthesis as a result of their inhibition of theenzyme DNA gyrase. The activity of this enzymeis necessary to initiate DNA and RNA synthesis.



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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



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The Penicillins, which are bactericidal andqualitatively selective through their action indisrupting synthesis of bacterial cell walls, are not

generally used topically because of widespreadresistance and allergy problems. Selectedcompuonds, such as ticarcillin, carbenicillin,piperacillin are used by other routes forPseudomonas infections.



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Introduction

Antibiotic therapy




(NSAIDs)

Conclusions




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Antibiotics for Specific Ophtalmic

Conditions

It is well known that the initial therapy for suspectedbacterial 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.

Bacterial keratitis

Cameron N Ly MB BS;Clinical 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.



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bacterial keratitis

Cameron N. and coll. performed a quantitative

susceptibility testing to six antibiotics on all

bacteria isolated from 112 patients whopresented to the Sydney Eye hospital

Emergency Department with presumed bacteria

keratitis.



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bacterial keratitis

Bacterial species

isolated from cornealscrapings taken from

112 patients with

suspected bacterial

keratitis.

Cameron N Ly MB BS;Clinical and

Experimental Ophthalmology 2006


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bacterial keratitis

Antibiotics used in thestudy. The initialtopical antibiotic

treatement is shown inthe black bar and thenumber of successfulcases shown in theshaded bar.

Cameron N Ly MB BS;Clinicaland ExperimentalOphthalmology 2006


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bacterial keratitis

The mentioned study showed that cephalosporins andaminoglycosides were complementary in their microbial

cover.

The Cephalosporin plus aminoglycoside combinationtherapy has proven an effective initial broad-spectrumtreatement of bacterial keratitis in many other studies in

London, Sweden and the USA.



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bacterial keratitis

The use of fluoroquinolones has been shownto be an effective alternative for the usual

cephalosporine and aminoglycosidecombination therapy, as demonstrated inlarge prospective multicentre studies thatsupported the use of 0,3% ciprofloxacin

topical monotherapy and 0,3% ofloxacintopical monotherapy.



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bacterial keratitis

Ciprofloxacin is also one of a fewantibiotics that enters the human eye after

oral administration.



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bacterial keratitis

Distribution of ciprofloxacin minimum inhibitory concentration (MIC).

Fifty-one out of 53 isolates were likely to respond to ciprofloxacin

(MIC


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Conditions

Conjunctivitis

Most cases of conjunctivitis have a viral etiology, with

prominent symptoms being itchy, watery, red eyes with lidand conjunctival edema. In this case eyedrop antibioticsare useful to prevent a secondary bacterial infection.

Good choises include:

- Polytrim- Tobramycin

Richmond Eye Associates; Ophtalmology Update Jul 2001


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Conditions

Conjunctivitis


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ConditionsConjunctivitis

Bacterial conjunctivitis is characterized by a copious purulentdischarge.

Good antibiotic choises include:

- Polytrim- Ocuflox

- Gentamycin

- Tobramycin

- Neosporin



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Conditions

Conjunctivitis

Chlamydia Trachomatis is a cause of chronic

conjunctivitis and appropriate systemic

treatement is indicated along with Erythromycin

ophthalmic ointment.



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Conditions

Prophylaxis of corneal abrasions

Antibiotics eyedrops or ointments should be used during

the healing period of corneal abrasions to preventcorneal 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)



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Conditions

Blepharitis

For significant flare-ups of the condition, antibioticoinments 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 maygive more rapid relief.



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Conditions

Blepharitis


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Conditions

Endophthalmitis

John P Witcher, West J Med 1994


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Conditions

Endophthalmitis


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Antibiotics in ocular tuberculosis

The most common manifestation of the ocularinvolvment in tuberculosis is uveitis, usuallypresenting as a chronic anterior uveitis,panuveitis or as a choroiditis.

In the posterior ocular pole it is possible to findchoroidal 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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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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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.


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Introduction

Antibiotic therapy




(NSAIDs)

Conclusions




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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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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


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Steroidal anti-inflammatory drugs:

mechanisms of action

Their antiinflammatory and immunosuppressive

action can be related to the following actions:

Inhibition of lymphocites proliferation, above alllymphocytes 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 neutrophilgranulocytes, macrophages, mastcells and

basophil granulocytes. Decrease of vascular permeability

Decrease of Prostaglandines production asconsequence of the suppression of arachidonic

acid synthesis.



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Prednisolone

Studies shows that Prednisolone has the greatest anti-inflammatory efficacy of all topical ophthalmic steroids.

Prednisolone acetate 1% is the most effective of thetopical ophthalmic steroids for the treatement of uveitisand 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


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Dexamethasone

In its approved concentration, Dexamethasoneis less clinically effective than prednisolone andhas a greater tendency to raise intraocularpressure, making it a drug of second choise.



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Fluorometholones

They possesses good to excellent anti-

inflammatory properties , while having adiminished propensity to cause secondary IOPincrease.

There are two formulations of fluorometholone,the alchool and the acetate.



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Fluorometholone alchool

It is used very commonly to treat a host of mildto moderate ocular scurface inflammatoryconditions, requiring long-term (beypnd three tofour week) therapy such as low-grade chroniciridocyclitis and some cases of ocular allergy.

Its usefulness in chronic care lies in its reducedtendency to cause secondary IOP increase.



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Fluorometholone acetate

This is the more clinically active formof the more

familiar FML. The acetate formulation confers tofluorometholone greater clinical efficacy.

The indications for this product are essentiallythe sae for the other corticosteroids.



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Rimexolone

It is a potent, relatively safe preparation,

and it is close to, but not as effcacious as1% prednisolone acetate; yet itsdecreased propensity to raise intraocular

pressure is very similar to that of thefluorometholones.


A tibi ti d ti i fl t


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Introduction

Antibiotic therapy




(NSAIDs)

Conclusions



N id l i i fl d


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(NSAIDs)

They are inhibitors of prostaglandines synthesiswith an anti-inflammatoey and analgesic activity.

The advantage of using them than steroidalagents is related to the fact that they do notinduce a decrease of immunosystem activity.

Moreover they do not interact with the ocularhydrodynamic.

O hth l i t id l ti


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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 tothe prostaglandines may result in increased production ofleukotrienes which are also inflammatory.

This may have serious consequances for some patients,e.g asthmatics, as the leukotrienes causebronchoconstriction.


O hth l i t id l ti


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inflammatory drugs

Currently they are used in intra- and/or post-operative situations to reduce miosis duringsurgery and inflammation following cataract

surgery, laser trabeculoplasty and PRK.

They are also used in the prevention andtreatment of cystoid macular oedema and for thetreatment of allergic conjunctivitis.

Vale J; Ophthalm Physiol Opt 1998

O hth l i t id l ti


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inflammatory drugs

Other therapeutics indications of NSAIDs in oculardiseases are:

- Inflammations of the anterior segment of the eye, whichdo not recognize a viral o bacterial etiology, such ascorneal and conjunctical edemas, scleritis.

- Inflammatory reactions due to traumas

- Cornela neovascularization due to the use of contactlenses and its following inflammation.

Vale J; Ophthalm Physiol Opt 1998

O hth l i t id l ti


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inflammatory drugs

The topic NSAIDs actually in commerce all over the Europe are:

- Diclofenac sodico

- Flubiprofene sodico

- Ketorolac trometamina

- Piroxicam

- Indometacina

- Suprofene


Antibiotic and anti inflammatory


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Introduction

Antibiotic therapy




(NSAIDs)

Conclusions



C l i


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Infections of the eye can rapidly damage important functionalstructures 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.

Conclusions


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Is important to make a clinical diagnosis before treatment andof following the clinical course of patients carefully duringtreatment

Because of the potential for side effects, treatment must beindividualized and regular monitoring performed.

With careful use of immunosuppressive drugs for treatmentof ocular inflammatory disorders, many patients will benefitfrom them either with better control of the ocular inflammationor with a decrease in corticosteroid side effects.

Conclusions


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Grazie

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Farmaci in Oculistica1 - LA Rosa

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