Dry Eye Formulations

Dry eye

a disorder of the tear film due to tear deficiency or by excessive tear evaporation which causes damage to the interpalpebral ocular surface. It is associated with symptoms of ocular discomfort including burning, itching, and blurred vision. It can involve ocular surface inflammation which in severe cases can cause secondary keratitis, conjunctivitis, corneal ulceration, and corneal scarring which can lead to permanent vision loss.

Aqueous deficient dry eye (keratoconjunctivitis sicca)

dry eye which occurs due to decreased tear volume secondary to a disorder of the lacrimal gland function or failure of lacrimal fluid to transfer. Is the largest category of dry eye cases.

lacrimal disease

lacrimal obstruction

reflex

three main contributing factors for Non-Sjogren's aqueous deficient dry eye

Evaporative dry eye

dry eye which occurs due to meibomian gland dysfunction or increased palpebral fissure width that leads to increased evaporation, or an anomaly of tear distribution in the presence of a functional lacrimal gland.

lipid layer

layer of the tear film composed of waxy and cholesteryl esters as well as some polar lipids.

mucus layer

the thickest layer of the tear film composed of mucoproteins rich in sialomucin.

corneal afferent nerves

brainstem efferent nerves

lacrimal glands

name the three steps in the pathway of tear production

cytokines

hormone like proteins that regulate T cell proliferation and differentiation. Can damage tissues when released in overabundance, as seen in dry eye disease. This can then lead to a decrease in ocular surface sensitivity due to disruption of sensory signals. Decreased sensitivity affects the stimulus for tear secretion causing decreased tear production and clearance.

Neurogenic inflammation

T cell activation

Inflammation may cause damage to lacrimal glands via these two events

activation of T cells

Production of inflammatory substances

Inflammation

Tissue damage

Infiltration of glands with T cells leads to further... (4 answers)

reduction of corneal sensitivity

Refractive surgery such as PRK and LASIK are known to cause aqueous deficient dry eye via the...

o Draw water from epithelial cells

o Interfere with metabolism

o Decrease cell vitality

o Reduce microvilli disrupting stability of the mucin layer

4 affects of hyperosmolar tears on the cornea

increased tear tonicity

Patients having keratoconjunctivitis sicca have _____ when compared with normal individuals. Some dry eye formulations are hypotonic in an attempt to dilute and decrease osmolarity of the tear film.

androgens

hormones that regulate meibomian gland function and promote the formation of the tear film's lipid layer. Therefore, its insufficiency may contribute to meibomian gland dysfunction, tear film instability, and evaporative dry eye. Its topical application may be an effective therapy for dry eye.

o Replicate metabolic, optical, and physical characteristics of natural tears

o Long contact time

o Contain additives to treat primary and secondary ocular damage

3 ideal characteristics of artificial tear solutions

8.5, corneal epithelial barrier

Artificial tears with a pH of ____ are most comfortable for dry eye patients. Bicarbonate ions significantly enhance the _____

o Methylcellulose

o Polyvinyl alcohol

o Povidone

o Dextran

o Propylene glycol

five Polymers added to artificial tears to increase contact time

Preservatives

are added to slow microorganism growth in multidose formulations

Benzalkonium chloride (BAK)

preservative whose overuse of 0.004% and 0.02% concentrations may be toxic to the tear film and cornea and thereby decrease TBUT.

Chlorobutanol

preservative that is associated with allergic reactions

Thimerosal

preservative that causes little epithelial damage, but is associated with allergic reactions

Ethylenediaminetetraacetic acid (EDTA)

preservative that chelates the calcium required for cell junction formation and may be cytotoxic with prolonged use.

Methylparaben

Propylparaben

two paraben preservatives added to artificial tears

Sodium perborate and purite

two newer preservatives that are not toxic to the eye because they are converted to oxygen and water upon contact

three to four

Unpreserved artificial tears are recommended for patients with dosing schedules that exceed ____ times a day

nutrients

are added to artificial tears to support corneal and conjunctival epithelial metabolism, as well as the synthesis of mucin and glycocalyx

o Dextrose

o sodium lactate

o sodium citrate

o vitamin a

o vitamin b12

o vitamin c

six nutrients added to artificial tears to support corneal and conjunctival epithelial metabolism, as well as the synthesis of mucin and glycocalyx

vitamin a

vitamin added to artificial tears as it is essential for the differentiation and maintenance of mucosal epithelium. It increases mucous, aqueous, and lipid components of tears.

Electrolytes

are added to artificial tears to help maintain or to low tear osmolarity. Are important for corneal epithelial metabolism and as part of a buffer system.

sodium chloride

potassium

two electrolytes added to artificial tears to help maintain or to low tear osmolarity. Are important for corneal epithelial metabolism and as part of a buffer system.

serums

have been shown to significantly increase mucin expression in Sjogren patients

o time consuming preparation

o short storage time

o handling difficulties in patients with transmissible diseases

three disadvantages to the use of serums in artificial tears

HYDROXYPROPYL GUAR (HP GUAR)

a viscosity enhancing agent present in Systane eye drop formulation. Is designed to mimic the mucin layer of tears in order to prolong contact time and to promote the retention of the drug. Forms a gel at pH of 7.5.

hypotears

theratears

two artificial tears that decrease tear film osmolarity

ACETYLCYSTEINE (MUCOMYST)

a mucolytic agent utilized to soften mucus in conditions such as vernal or giant papillary conjunctivitis and filamentary keratitis associated with aqueous deficient dry eye. It is applied topically to dissolve mucous threads and decrease tear viscosity.

mucomyst

What is the trade name for acetylcysteine?

LACRISERT (MERCK)

a water soluble rod containing 5 mg hydroxypropylcellulose that is placed in the inferior fornix. It is used to relieve symptoms by increasing TBUT and thickening the tear film.

o discomfort

o blurred vision

o tear secretion is necessary to dissolve the insert

three disadvantages of lacrisert

BIOTRUE HYDRATION BOOST

eye drop enhanced with hyaluronic acid that is a natural moisturizer that helps to maintain ocular surface homeostasis. Is compatible with contact lenses.

o Control of environmental factors

o Ophthalmic ointment

o Lacrimal drainage system obstruction

Tear conservation can be achieved via these three methods

LACRILUBE AND REFRESH PM

two ophthalmic ointments marketed by Allergan

o Insoluble in water (do not mix with tear film)

o Reduce TBUT

o Blurred vision

o Cannot be used on compromised cornea

4 Drawbacks of Ophthalmic Ointment

Punctal plugs

collagen (4-7 days) or silicone pieces that are inserted into the inferior punctum or canaliculus to prolong the action of natural tears by blocking tear drainage.

o Insertion is difficult

o Plugs can fall out

o Epiphora

o Ocular irritation (due to retention of inflammatory cytokines)

o Canaliculitis

five Drawbacks of Punctal Plugs

PILOCARPINE

BROMHEXINE

two secretagogues used to stimulate tear production

TRUE TEAR

a recently FDA approved handheld device used to stimulate neural tear lacrimation. It works by stimulating a nerve in the nasal cavity via tiny pulses of energy.

DIQUAFOSOL TETRASODIUM

a potent and selective P2Y2 receptor agonist that can be administered four times a day as a non-preserved drop.

P2Y2 receptors

receptors present in the epithelial cells of the ocular surface. When they are stimulated by ATP there is an increase in mucin like glycoprotein secretions by conjunctival goblet cells and increased aqueous production by the lacrimal glands. These receptors may also play a role in the lipid composition of meibomian gland secretions. Agonists of these receptors can thereby have beneficial effects of all layers of the tear film in the treatment of dry eye.

VARENICLINE (TYRVAYA)

a nasal pray that is known to activate the trigeminal parasympathetic pathway via the nose resulting in increased tear film production.

LIFITEGRAST 5% (XIIDRA)

an integrin antagonist that prevents the binding of LFA1 to ICAM1 decreasing inflammation of the ocular surface and thereby improving dry eye disease. Is recommended to be applied twice daily.

xiidra

trade name of lifitegrast 5%

REGENER-EYES

a natural biologic ophthalmic solution that is preservative free. Contains numerous anti-inflammatory cytokines and growth factors from placental derived tissues that aid in cell function and homeostasis. These include VEGF, TGF beta1, EGF, PDGP and collagens I, III, and IV.

VEGF

TGF beta1

two anti-inflammatory cytokines contained in regener-eyes

EGF

PDGF

two growth factors contained in regener-eyes

I, III, IV

three collagen types contained in regener-eyes

methylprednisone

loteprednol

two corticosteroids which can be used to reduce inflammation in dry eye

alrex, lotemax

two trade names of loteprednol

EYSUVIS

an ophthalmic suspension containing 0.25% loteprednol preserve with BAK.

CYCLOSPORINE (NEORAL, SANDIMMUNE)

immunomodulator that inhibits T cell activation and is used principally in autoimmune disease or to prevent transplant rejection but can also be used to reduce the inflammatory response of the ocular surface and lacrimal glands seen in dry eye disease

neoral, sandimmune

two trade names of oral cyclosporine

RESTASIS

a 0.05% preservative free emulsion of cyclosporin that can be used twice daily.

CEQUA

o a 0.09% cyclosporin solution that overcomes solubility difficulties seen in Restasis and is thereby able to penetrate the eye's aqueous layer of the tear film.

0.002% CENEGERMIN (OXERVATE)

a human nerve growth factor solution that can be instilled six times a day at two-hour intervals for eight weeks to help the re-epithelialization of non-healing epithelial defects associated with neurotrophic keratopathy

oxervate

trade name of 0.002% cenegermin

omega 3s

fatty acids that enhance meibomian gland function

n3

fatty acids that reduce inflammation

n6

fatty acids that inhibit the formation of arachidonic acid

THERATEARS

a capsule supplement containing flaxseed oil, eicosapentaenoic acid, and docosahexaenoic acid (essential fatty acids). Is useful for treating ocular surface disease because it decreases inflammation and enhances lipid and aqueous production.

REFRESH OPTIVE

a preservative free, low blur lipid based artificial tear that contains flaxseed oil and other essential fatty acids. Helps to fortify and restore the lipid layer of the tear film. Is especially useful in the treatment of dry eye associated with meibomian gland dysfunction. Marketed by Allergan.

SYSTANE BALANCE

a lipid based artificial tear containing mineral oil. Marketed by Alcon.