Transcript Ophthalmic Products

Ophthalmic Products
Dr. M. Wazaify
University of Jordan
Why study ophthalmic products?
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Many common conditions cause ocular
discomfort are minor and self-limiting.
However, relatively minor symptoms may be
associated with severe, potentially blinding
conditions
Thus, pharmacists should provide best
possible guidance to patients who seek
assistance in choosing between selftreatment or professional medical care
Eye Anatomy & Physiology
External Eye
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1.
2.
3.
Location: susceptible to environmental and
microbial contamination
Many natural defence mechanisms to
protect against such contamination:
Eyelids
Eye-lashes
Tears
1. Eyelids
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a multi-layer tissue, covered externally by
the skin and internally by a thin,
mucucutaneous epithelial layer (conjuctiva).
It contains 5 glands: meibomian, Zeis & Moll
(sebaceous) + Krause & Wolfring’s
(lacrimal)
The eyelids play important roles in the eye
1. Eyelids
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The functions of eyelid: (1) protect front
surface of the eye neural reflex
mechanism blocks contaminants from
reaching ocular surface
(2) spread the tears produced by lacrimal
glands
(3) close by zipperlike manner force the
tears towards the nose drainage
2. Eye-lashes
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Collect debris before it encounters the eye
N.B. The lacrimal drainage system is lined by
a highly vascularised epithelium and &
absorption into systemic circulation along this
pathway gives rise to potential systemic
effects of topically administered eye
medication
3. Tears
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1.
2.
3.
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Functions of the tears:
Lubricating ocular surface
Provide mechanism for removing debris
drainage
Potent antimicrobial action (e.g. IgA, enzymes)
Rate of tear production: 1-2 L/min (7-10 L
is found on ocular surface at any point)
Upon irritation: tear production increases
300%
3. Tears
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The tear film is a tri-layer film:
Outer (by sebaceous glands): lipid, prevent the
evaporation of the tears,
Middle (by lacrimal lands): the largest layer,
aqueous, responsible for wetting properties
Inner (by goblet cells): mucinous, allows the lipid
and aqueous layers to maintain adhesion
across the cornea and conjuctiva
Abnormalities in any of these layers causes ocular discomfort
External Eye
The visible external eye consists of the
sclera + cornea
1.
Sclera: a tough, collagenous layer that
gives the eye rigidity & encases internal eye
structures
 Covered by 2 epithelial layers: epi-sclera
+ bulbar conjuctiva, contain the vascular &
lymphatic systems of the anterior eye
surface the source for visible eye redness
during irritation & inflammation
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External eye
2.
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Cornea: aspherical, avascular tissue that is
the principal refractive element of the eye
Consists of 5 layers: epithelium, Bowman’s
layer, the stroma, Descemet’s membrane &
endothelium
The unique anatomic structure of the eye
affects drug absorption. HOW?
Drug absorption through
cornea
Corneal epithelium is lipophilic: facilitates
passage of fat-soluble drugs
Corneal stroma is hydrophilic: allows
passage of water-soluble drugs
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Thus, optimum penetration of a drug through the
cornea depends on biphasic solubility
Damage to corneal epithelium may markedly affect
drug absorption rates
Comparative studies showed that drug penetration to
the aqueous layer increased to threefold in
compromised epithelium
Factors that may compromise
epithelium:
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Trauma
Routine contact lens wear
Topical ophthalmic anaesthetics
Thermal or UV light exposure
It was found that: as much as 90% of the dose instilled in
the eye may be lost. WHY IS THAT????
Factors that may hinder efforts to
maintain therapeutic drug level in the
eye
1.
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Difficulty of drug to penetrate through the
cornea
Dilution of the drug by reflex tearing (e.g. 2.5%
NaCl 0.9-0.95% within 1-2 minutes)
3.
Rapid removal of drug through the tear
system
Internal Eye
1.
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3.
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Anterior chamber
(behind cornea): contains
aqueous humour a. maintains normal internal eye
pressure; b. provides nutritional support for lens &
cornea
Iris: visible coloured portion of the eye
 regulates light striking retina, contains 2
types of muscle (sphincter & dilator)
Pupil: central opening of iris,
Prostaglandins secreted by iris during an inflammation
stimulates sphincter muscles  reduces the pupil diameter
This helps to distinguish simple external eye irritation from
severe internal inflammation
Internal Eye
4.
5.
Crystalline lens: avascular, biconvex structure
that alters its shape to focus light on retina
“accommodation”
Ciliary body= ciliary muscle + epithelium
- the contraction of ciliary muscle helps in
“accomodation”
- during inflammation spasm of ciliary muscle
fluctuating vision and pain. Thus, inhibition of ciliary
muscle (cycloplegia) by anticholinergic drugs
frequent treatment drug of internal ocular
inflammation
Internal Eye
6.
Vitreous Body:
(80% of total eye volume), filled
with vitreous humour, a gel like, fluid collagen
matrix that helps maintain eye volume
7.
Retina: multi-layer neural tissue that begins
the visual pathways (capture light, rods & cons,
photic message optic nerve to posterior cerebral cortex
visual information decoded)
Common Ocular Disorders
• Eyelid Disorders
• Ocular Surface Disorders
• Internal Eye Conditions
Common Ocular Disorders
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Ocular inflammation and irritation can be caused by
many conditions, some of which can be treated safely
and effectively by OTC drugs
OTC drugs relieve minor symptoms: burning, itching,
stinging and watering
FDA suggested self-treatment indications:
-
tear insufficiency
corneal edema
external inflammation & irritation
Hordeolum (stye)
- blepharitis
- conjuctivitis
Common Ocular Disorders
Referral is mandatory:
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Embedded foreign body
Uveitis; ”uvea: middle coat of the eyeball, the choroid, ciliary
body & iris as a whole”
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Flash burns
Chemical burns
Tear duct infection
Corneal ulcer
Chemical eye burn
Thermal burn
1. Eyelid Disorders:
Blunt Trauma:
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Highly vascularised eyelid blunt
traumableeding swelling and ocular discomfort
Mostly, blunt trauma does not result in internal
damage & treatment is usually supportive: A. cold
compresses; B. Oral OTC analgesics
However,all individuals should be evaluated by an
optometrist or ophthalmologist ASAP after the event
Complications: internal eye bleeding, secondary
glaucoma, retinal detachment
1. Eyelid Disorders:
Belpharitis (Very common)
 Almost always due to Staphylococcus
epidermidis or Staphylococcus aureus
 Typical: red, scaly, thickened eyelids, often with
loss of eyelashes, itching & burning (most
common)
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Acute or Chronic (patients aware of diagnosis)
Treatment: hot compress, topical antibiotic &
eyelid scrub using an OTC eyelid hygienic
preparation (baby-shampoo)
1. Eyelid Disorders:
Lice Infestation
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Phthirius Pubis (crab louse) & Pediculus
humanus capitis (head louse)
May cause symptoms similar to those of
blepharitis
Peduculicides (=lice shampoos: NIX, RID, A200) should not be used around the eye
hypersensitivity reaction
Lice Infestation
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2.
Treatment:
A bland ophthalmic ointment (e.g.
petrolatum) used for 10 days effective
because it suffocates the louse and deprives
its eggs of oxygen
Hygienic measures: wash clothing & bedding
that may contain unhatched eggs
Crab louse
eyelid
1. Eyelid Disorders
Contact Dermatitis
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Cause: changing make-up , soap, exposure
to some foreign substance
Symptoms: swelling, scaling of eyelid with
profuse itching
Usually both eyes are involved suggests
allergy (ask patient about newly used products)
Treatment: (1) best treatment is removal of
offending substances; (2) OTC oral
antihistamines; (3) cold compresses
1. Eyelid Disorders
Hordeolum (stye)
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Mebomien gland
(internal hordeolum)
Inflammation of either
Zeis & Moll glands
Palapable, tender nodule (external hordeolum)
Cause: Staphylococcus epidermidis or
Staphylococcus aureus
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Treatment: (1) Hot compresses 3-4 times/day (510 minutes; clearing within 1 week); (2) External
hordeolum topical antibiotic; Internal hordeolum
oral antibiotic; (3) if resistant surgical drainage
Internal
hordeolum
External
Hordeolum
Recurrance of chalazia & hordeola maybe reduced by periodic use of
lid scrubs
1. Eyelid Disorders
Chalazion
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painless, slowly enlarging nodule on the
eyelid formed by inflammation of the
meibomian glands (deep chalazion) or Zeis
sebaceous glands (superficial chalazion).
difference:1. not tender to gentle touching
and is painless. 2. 3. ???
Treatment: (1) hot compresses (2) oral
antibiotics (3) if resistant
Intra-lesional steroid
injection
surgery
2. Ocular Surface Disorders
Foreign substance contact
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If reflex tearing does not remove the foreign
substance, the eye may need to be flushed with
sterile saline or specific eye wash preparations
(irrigants: witch hazel, baby shampoo)
If trapped up the eye lid may not go with
flushing optometrist or ophthalmologist
Metallic foreign body NOT SELF-IRRIGATION
(abrasion, scarring, chronic red eye)
 Immediate medical referral
2. Ocular Surface Disorders
Abrasions
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“superficial injury to a skin or mucous membrane, in
this case, the cornea or conjuctiva”
Causes: Scratches by fingernails or by foreign bodies
Such injuries cause partial or total loss of the
epithelium & are painful especially if cornea is involved
Self –treatment NOT RECOMMENDED because of the
risk of bacteria or fungi contaminating and infecting the
eye
2. Ocular Surface Disorders
Chemical Exposure
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Splash injury, fumes or solid chemicals
serious problem Medical Emergency
immediate referral to A&E department
Initial treatment: flushing eye with sterile
saline or water for at least 10 minutes
Chemical burn of the
cornea
2. Ocular Surface Disorders
Thermal Damage
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Ranges
Minor
e.g. exposure to UV
radiation during skiing
Treatment: artificial
tears, ointments
Severe
e.g. welder's arc
(acute UVkeratoconjuctivitis)
Refer to Doctor
Minor thermal burn
Major thermal burn
(Welder’s arc)
2. Ocular Surface Disorders
Conjuctivitis: inflammation of bulbar
conjuctiva
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Viral conjuctivitis
Allergic conjuctivitis
Bacterial conjuctivitis
Chlamydial conjuctivitis
Usually self-limiting, with symptoms resolving 1-3 weeks
Viral conjunctivitis
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Pinkey
e
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The most common conjunctivitis
Causes: recent cold, sore throat, exposure to
someone with pink eye (acute contagious
conjunctivitis)
Symptoms: “pink-eye” with copious amounts of
watery discharge; nondescript ocular discomfort; mild
to moderate foreign body sensation; occasionally
blurred vision; low grade fever, swollen lymph nodes
Treatment: relief major symptoms using artificial
tears & ocular decongestants.
Certain forms are extremely contagious: wash hands,
do not share towels, properly dispose of tissues used
to blot the eye
Allergic conjunctivitis
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Caused by many antigens (Ag): pollen
grains, animal dander & topical eye preparations
Symptoms: red eye with watery discharge
Hallmark symptom: itching
Afflicted people often report seasonal allergic
rhinitis
Ask patient about recent exposure to Ag
Treatment: removal of cause (best); ocular
decongestants and antihistamines; oral
antihistamines; cold compresses
Bacterial conjuctivitis
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Staphylococcus epidermidis, Staphylococcus
aureus, Heamophilus influenza &
Streptococcus pneumoniae
Symptoms: red eye with purulent discharge
Key symptom: eyelids sticking together on
awakening
Self-limiting within 2 weeks, but topical
antibiotics may clear the symptoms more
quickly
Chlamydial conjuctivitis
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Classified as sexually transmitted disease (STD)
Often initially misdiagnosed with bacterial & viral
conjunctivitis, because of common signs and
symptoms
Misdiagnosis is a problem: (1) as such
individuals may harbor other STDs & (2)
bacterial and viral conjunctivitis are self-limiting
Discourage self-treatment if symptoms are
vague
Keratitis
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Inflammation of the cornea
Either separate or with other kind of
conjunctivitis
Potentially vision threatening problem
Symptoms: those of conjunctivitis+1 or more
additional symptom (pain, photophobia, blurred vision)
Complications: corneal ulceration or even loss of
eye (especially in those who sleep with contact lens
overnight) WHY?
Pseudomonas aureginosa “the most common cause of corneal
ulceration among contact lens wearers” produces collagenase
that can destroy the cornea within 24 hours
Corneal Oedema
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WHY?
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Oedematous area of cornea: epithelium
Causes: over-wearing of contact lens,
surgical damage to cornea, inherited cornea
dystrophies
Hallmark symptom: halos or starbursts
around lights, with or without reduced vision
because: accumulation of fluid distorts optical
properties of cornea
Treatment: apply hypertonic saline solution or
ointment (2-5%) to dehydrate cornea
Corneal Edema
Dry Eye
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Contrary to what
the name
suggests
Very common eye disorder
Symptoms: white or mildly red eye, sandy
or gritty feeling & excess tearing
Any abnormality in tear layers less
lubrication to ocular surface leads to
production of more inadequate tears
“vicious cycle”
What are the causes of dry eye?
Dry Eye
Treatment:
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OTC lubricants and artificial tears
(drops or
ointments)
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Vitamin A: greatest benefit in treatment of
severe dry eye associated with glandular
tissue destruction
Ocular inserts of
If very severe dry eye:
Na hyaluronate
Occlusion of lacrimal drainage
system to increase available tear
pool
How does artificial tears work?
Compromised Tear
Film
For dry eye
sufferers, dry spots
on the surface of
the eye cause
irriation, and may
create the
potential for more
serious damage to
the surface of the
Artificial Tears
drop of
artificial
tears
The artificial tear
solution is quickly
absorbed and key
ingredients rapidly
work to help
restore the tear
film.
All layers of the
normal tear film
are restored
Lubricants
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A.
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solutio
ns
ointments
solutions/ointments that help to alleviate dryness of
ocular surface
MOA: increase viscosity of existing tears, retard
drainage and increase retention time.
However, although viscous agents enhance the ocular
retention time of tear substitutes, high viscosity itself
does not provide relief for all dry eye conditions
(Pharmaceutical Journal; 264 (7082):212-218; 2000)
Artificial Tear Solutions (Demulcents)
water-soluble polymers
Administered 3-4 times daily
1. Cellulose ethers:
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HPMC (hypromellose) ; HPC, HEC,
methylcellulose, carboxymethylcellulose
Colourless and vary in viscosity
Methylcellulose 0.2-1.0%, if >2% ointment
HEC & HPC solutions: are less viscous but have
greater emollient (cohesive, film-making)
properties than methylcellulose
The most important property of cellulose ethers:
stabilize tear film (surface active properties) and
prevent evaporation
Lack toxicity & irritation
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Other less viscous hydrophilic substances, such as
polyvinyl alcohol (PVA) and polyvinyl pyrrolidone
(povidone or PVP), have been included as the
polymeric ingredients of many artificial tear
formulations.
The tears of patients with dry eyes due to aqueous
deficiency have been shown to have a higher
osmolarity than normal subjects, a factor which may
be responsible for the ocular surface disease in this
condition.
In such patients, hypotonic solutions such as polyvinyl
alcohol 1 per cent with an osmolarity of 150 mOsm/L
have been shown to be superior to an isotonic solution
of 300 mOsm/L in providing symptom relief.
2. Polyvinyl Alcohol
Important: avoid using PVA with ophthalmic
products that contain: NaHCO3, Na-Borate,
Na/K/Zn sulphate…..
Cause:  it will react and form a thick gel
e.g. PVA-containing contact lens wetting
solution & irrigants containing Na-Borate
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3. Povidone (polyvinyl pyrrolidone;
PVP)
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Exerts surface active properties similar to
those of cellulose ethers forms hydrophilic
layer on corneal surface, mimicking
conjunctival mucin promotes wetting of
ocular surface
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Patients with mild dry eye may benefit from
instillation of one of these artificial tear drops
up to four times a day.
However, in moderate to severe cases, these
preparations need to be instilled more
frequently.
To overcome this problem, preparations
containing a longer-acting polymer,
polyacrylic acid, also known as carbomer
940, have been introduced. Such
preparations have a much longer retention
time in the eye and symptom relief is
obtained with significantly fewer instillations.
In Jordan:
PVA+PVP
CMC
PVA+1%
polyethylene
glycol
4. Retinol Solution
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An alcohol form of vitamin A
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What is the mechanism of action?
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Retinol palmitate aqueous ophthalmic
solution is used for the treatment of dry eye
failing to respond to the conventional therapy
with artificial tears;
The benefits of vitamin A in treatment of dry
eye are speculative (lack controlled trials)
Note: (Benzalkonium Cl)
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Benzalkonium chloride (BAK) is a poor choice
preservative for artificial tear solution,
because it has toxic effects on tear film &
corneal endothelium*
A single drop BAK can break the lipid
superficial layer of tear film into numerous oil
droplets
Alternative preservatives: chlorhexidine,
chlorbutanol, EDTA
* Reference: Lemp MA, Zimmerman LE. Toxic endothelial degeneration in ocular surface
disease treated with topical medications containing benzalkonium chloride. Am J Ophthalmol
5. Preservative-Free
Formulations
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For patients who are sensitive to
preservatives like benzalkonium chloride
(BAK) & thimerosal*
Formed as unit-dose dispensers
More expensive than products with
preservative.
Requires strictly hygienic procedure: easy to
get contaminated
Discard any unused solution after 12 hours
* Reference: Lee-Wong M, Resnick D, Chong K.A generalized reaction to thimerosal from
an influenza vaccine. Ann Allergy Asthma Immunol. 2005 Jan;94(1):90-4.
Evidence Based!
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Göbbels and Spitznas have shown a decrease in
epithelial permeability in patients treated with
unpreserved PVP 2%, while those receiving the same
preparation preserved with BAK 0.005% showed an
increase in permeability.
The authors suggest that, in dry eyes, treatment with
unpreserved artificial tears may lead to an objective
improvement in corneal surface disease, with this
effect being counteracted by preservation of tear
substitutes with BAK.
Reference:
Göbbels M, Spitznas M. Corneal epithelial permeability of dry eyes before
.
and after treatment with artificial tears. Ophthalmol 1992;99:873-8
However,……
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It is unlikely that patients purchasing dry eye
products OTC would wish to bear the cost of
unit dose preparations unless they fall into
the category of patients in whom preserved
eye-drops are contraindicated.
WHO ARE THEY??
1. patients allergic to, or intolerant of, preservative and
2. patients who wear soft contact lenses.
BREAK
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What gives the cats eyes the characteristic
night-time glow when they are caught in a
beam of light?
A feature, which enables the amount of light
hitting the retina to be increased, is the
tapetum lucidum. This is positioned at the
back of the eye, behind the retina and acts
like a mirror, reflecting light back onto the
light sensor cells in the retina.
B. non-medicated
ointments (Emollients)
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2.
Main advantage: melt at the temperature of
the ocular tissue and are retained longer than
other ophthalmic vehicles enhance integrity
of tear film
Preferably instilled at bedtime:
To keep eyes moist during sleep & improve
morning symptoms of dry eye
Because they cause blurred vision
e.g. white soft paraffin, lanolin and liquid paraffin.
Decision Making Algorithm
RED EYE
Clinical presentation
Management
With pain
With blurred vision
With photophobia (light
sensitivity)
With history of trauma
With contact lens wear (??)
IMMEDIATE
REFERRAL
Decision Making Algorithm
RED EYE
Clinical presentation
Management
With history of pink eye
exposure, cold, flu,
and watery discharge
Self-treatment
and mucous discharge
Referral
Decision Making Algorithm
RED EYE
Clinical presentation
With known allergies
and itching, watery discharge
and mucous discharge
Management
Self-treatment
Referral
Decision Making Algorithm
RED EYE
Clinical presentation
Management
With foreign body sensation
and possible contamination
and is elderly
Immediate Referral
Self-treatment
disorders that you don’t treat
in your pharmacy!
In addition to
keratitis and the
previous
algorithms
OTC
3. Internal Eye Conditions
Uveitis: inflammation of the uvea tract (iris, ciliary body
or choroid)
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Causes: trauma, systemic disease, idiopathic
Symptoms: v similar to viral conjuctivitis or
keratitis (mildly red eyes, pain, photophobia,
blurred vision)
Complications: secondary glaucoma,
destruction of iris or even blindness
Treatment: topical, depot or systemic oral
steroids depending on the cause. Selftreatment is not recommended
3. Internal Eye Conditions
Angle-closure glaucoma
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Caused by blockage of “trabecular meshwork”
drainage system of aqueous humour increase the
intraocular pressure
Occurs usually as pupil is returning to normal size
after the use of a mydriatic
Symptoms: painful eye, brow ache, headache,
nausea & vomiting
It is vision-threatening see doctor
OTC ophthalmic products
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Lubricants:
1. Artificial tear solutions (demulcents); 2.
Non-medicated ointments (emollients)
Decongestants
Antihistamines
Irrigants
Hyperosmotics
Antiseptics
Eyelid scrubs
Multivitamins
Decongestants
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Phenylphrine & Imidazoles (naphazoline,
tetrahydrozoline & oxymetazoline)
-adrenoceptor agonists vasoconstriction of
conjuctival vessels
If instilled to irritant/damaged cornea: dilate
pupil may precipitate angle-closure glaucoma
Systemic S.E: very rare at OTC dose
Caution in patients with CVD, HTN or DM
Decongestants
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Most common S.E if chronic use: rebound
congestion “hyperameia”
Rebound congestion is less with (naphazoline,
tetrahydrozoline) than with phenylephrine
and oxymetazoline
In some patients “Xerosis” (abnormal
dryness) with prolonged topical instillation of
local decongestants
Decongestants
Napahzoline (0.02%):
- The ocular decongestant of choice:
higher efficacy and relative lack of S.E
- in addition to constricting conjuctival vessels,
it reduces pain & tearing associated with
ocular inflammation
- Patients with lightly pigmented irides (blue or
green eyes) are more sensitive to the
mydriatic effects of naphazoline
Antihistamines
Pheniramine maleate & Antazoline phosphate
 Indication: rapid relief of symptoms associated
with seasonal allergic conjunctivitis
 Almost always used along with naphazoline: much
more effective than if used individually
 Dose: 1-2 drops applied to each eye 3-4 times
daily
 May cause mydriasis, because of anticholinergic
 C/I: sensitivity to one of the components or
known risk to angle-closure glaucoma
Irrigants
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Cleanse ocular tissues while maintaining their
moisture
Must be physiologically balanced: pH &
osmolality
Uses: (1) after certain clinical procedures to
wash away mucus & debris from eye (2) to clean
eyes in between changes of ocular dressings (3)
wash out eyes after wearing contact lens (4)
initial ocular lavage after chemical injuries to eye
before seeing doctor
Hyperosmotics
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Promote movement of fluid from cornea
NaCl: solution and ointment (2-5%)
5% is more effective, but causes stinging,
burning but 2% is preferable for long term use
1-2 drops instilled 3-4 times daily
Several instillations in the 1st few waking hours
are helpful as vision associated with corneal
edema is worse on awakening
Non toxic and very rarely to cause allergy
Antiseptics
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To reduce bacterial population on ocular
surface including eyelid margins
May be recommended for patients with minor
conjuctival or eyelid inflammation that is
possibly associated with infectious organisms
Examples: silver protein, Boric acid & zinc
sulphate, distilled witch hazel
Silver protein: A colloidal preparation of silver oxide and
protein, usually gelatin or albumin, used as an antibacterial agent.
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Treatment of ocular infections and preoperative use in
ocular surgery
At low doses: antimicrobial activity against gram +ve
and gram –ve bacteria
Preoperative: 2-3 drops instilled then rinse with sterile
irrigating solution
In mild infections: several drops instilled every 3-4
hours for several days
Avoid frequent topical application for prolonged periods
of time may cause permanent discoloration of eyelid
skin or conjunctiva “argyria”
Argyria
Boric acid
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Treatment of irritated, inflamed eyelids
Applied in small quantity on the inner surface
of the lower eyelid once or twice daily
Zn sulphate
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Mild astringent for temporary relief of minor
ocular irritation
Also effective in infections cause by moraxella
(uncommon gram –ve bacteria, member of the URT normal
flora, occasionally cause infections)
Eyelid scrubs
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Best treatment for blepharitis is maintain
eyelid hygiene
This is best done by hot compresses 15-20
minutes 2-4 times daily followed by eye lid
scrubs using baby shampoo with cotton pad
or a gauze
Application Technique 