Dry Eye Syndrome

Dry Eye (Keratoconjunctivitis Sicca)

“Dry eye is a multifactorial disease of the ocular surface
characterized by a loss of homeostasis of the tear film,
and accompanied by ocular symptoms, in which tear
film instability and hyperosmolarity, ocular surface
inflammation and damage, and neurosensory
abnormalities play etiological roles”

https://www.reviewofoptometry.com/CMSDocuments/2017/08/ro0817_DEWSIIi.pdf
Tear Film and Ocular Surface Society (TFOS) Dry Eye Workshop (DEWS) II
 Symptoms
The discomfort could be intermittent or continuous with mild
symptoms such as:
• Burning
• Itching
• Tearing
• Blurring of vision

• Severe cases: keratitis, conjunctivitis, corneal ulceration,

scarring, permanent vision loss
 Classification
of Dry Eye

Both lead to tear hyperosmolarity

Anthony J. Born.The Definition and Classification of Dry Eye Disease. C. Chan (ed.), Dry Eye: A Practical Approach, Essentials in
Ophthalmology, 1DOI 10.1007/978-3-662-44106-0_1, © Springer-Verlag Berlin Heidelberg 2015
 The Origins of Tear Hyperosmolarity

Tear hyperosmolarity may be brought about in two distinct ways,

which are the basis of the two major classes of dry eye:

1. Aqueous –deficient dry eye (ADDE)

2. Evaporative dry eye (EDE):

 Aqueous Deficiency
• Aqueous –deficient dry eye (ADDE): due to lacrimal disease
or dysfunction, whereby tear hyperosmolarity is caused by
evaporation from a reduced volume of tears

• Sjögren’s syndrome (SS): characterized by the triad of dry eye,

dry mouth (xerostomia), and a connective tissue disease

• Sjögren’s syndrome is treated with oral immunomodulatory

agents
• Non-Sjögren’s syndrome (non-SS): a reduction in tear volume
due to dysfunctional lacrimal gland or failure of lacrimal fluid
transfer.
 Evaporative Dysfunction

• Evaporative dry eye exhibits normal lacrimal function, but

meibomian gland dysfunction (MGD)

• Meibomian gland dysfunction causes a deficiency of the tear

film lipid layer, is the chief cause of EDE

• Evaporation can also be increased by a prolonged blink

interval, contact lens
 Evaporative Dysfunction

• MGD can be treated with warm compresses, lid massage,and

lid cleansing,with or without oral antiseborrheic agents (e.g.,
doxycycline 50 to 100 mg/day).

• All forms of dry eye are in fact evaporative, since tear

hyperosmolarity of consequence can only arise from
evaporative water loss.
 Diagnosis
History and examination followed by a symptom
questionnaire

• Fluorescein tear breakup time,

• Schirmer test,
• Ocular surface dye staining
• Tear film osmolarity,
• Tear fluid protein immunoassays
 Goal of Treatment

1. Relieve symptoms

2. Heal the ocular surface

3. Prevent serious complications

 Treatment
Tear supplementation: artificial tears,
lacrisert

Tear conservation: ointment, punctal

occlusion

Tear stimulation: secretagogues,

antiinflammatories/immunomodulators

Hormonal therapy

Omega-3 fatty acids

 Treatment: Tear Supplementation
• Artificial tear solutions: Polymer-based artificial tears.

The ideal artificial tear would:

1. Reproduce the metabolic, optical, and physical
characteristics of natural tears.
2. Additionally, it would have a long ocular residence time (tear
film stability).
3. and would contain therapeutic additives to treat primary and
secondary damage to the eye
 Treatment: Tear Supplementation
Most artificial tears are aqueous solutions consists of:

1. Polymers to enhance viscosity, lubrication and retention

time.
2. Electrolytes to maintain the osmolarity.
3. Buffers to maintain the osmolarity.
4. Preservatives to kill or inhibit bacterial growth.
5. Nutrients as supplements for conjunctival and corneal
metabolic requirements.
6. Mucolytic agents to soften the mucous and improve mucin
quality.
 Treatment: Tear Supplementation
1. Polymer-based artificial tears.
• Commonly used polymers: methylcellulose (MC) and
derivatives, polyvinyl alcohol (PVA), povidone
(polyvinylpyrrolidone [PVP]), dextran, and propylene glycol.
carboxymethylcellulose (CMC) added to enhance viscosity,
lubrication and retention time to promote tear film stability.

• Artificial tears are often classified as low, medium, or high

viscosity.

• For overnight use artificial tears are available in gel or

ointment formulations (transiently blurring vision)
 Treatment: Tear Supplementation
2. Electrolytes to maintain the osmolarity.

• Electrolytes such as salts of sodium and potassium are added

in the artificial solutions to maintain osmolarity and provide
nutrition for corneal epithelial metabolism.

• Most of the solutions are isotonic with natural tears.

• Hypertonicity in tear film causes cell shrinkage due to loss of

water, reduce cell viability and disrupts mucin layer.
 Treatment: Tear Supplementation
3. Buffers to maintain the osmolarity.

• The natural tear film components such as bicarbonates,

proteins, phosphates and others maintain a PH of 7.4.

• Commonly used buffer systems include phosphate,

phosphate-acetate, phosphate-citrate-bicarbonate.
Treatment: Tear Supplementation
4. Preservatives to kill or inhibit bacterial growth.
• Contaminated solutions are likely to cause infection in dry
eye.

• Multi-dose artificial tears are mandated by the FDA to contain

preservatives such as benzalkonium chloride (BAK) in order to
inhibit microbial growth, these are toxic in high quantities
(instillation more than 4–6 times/day).

• Patients requiring daily instillations of more 3-4 times are

recommended to use unpreserved solutions.
Treatment: Tear Supplementation
5. Nutrients as supplements for conjunctival and corneal
metabolic requirements.

• Nutrients are added to support conjunctival and corneal

metabolism.

• Water is most important component besides dextrose,

sodium lactate, sodium citrate, vitamin A and B12
Treatment: Tear Supplementation
6. Mucolytic agents to soften the mucous and improve mucin
quality.

• Example: bromhexine, acetylcysteine

• They soften the mucus and decrease the tear film viscosity.
• They stimulate the goblet cells for mucus production.
Artificial Tear Inserts
 Artificial Tear Inserts
• Lacrisert is a solid, water-soluble, cylindrical rod
approximately 1.25 mm wide and 3.5 mm long containing 5
mg of hydroxypropylcellusoe without preservative.

• When placed in the inferior sac, it imbibes fluid and swells to

several times its original volume.

• After initial swelling the insert dissolves over 6-8 hours.

• It is designed to be replaced every 24 hours.

https://www.youtube.com/watch?v=xUfDbBzan34
 Treatment: Tear Conservation
• Room humidifiers are a simple, non-invasive way of reducing
the evaporation of tears.

• Wearing tightfitting goggles,

• moisture chamber spectacles,

• Smoke, air conditioning, heat systems can aggravate dryness

by increasing evaporation.
 Tear Conservation: Ointments
• Non-medicated ointments are indicated for moderate to
severe dry eye.

• Petrolatum, mineral oil, lanolin serve as lubricants and create

a lipid layer, retarding evaporation.

• Patient acceptance of ointment preparations is highly

variable.
 Tear Conservation: Ointments
• They are not generally recommended for daytime use in
patients with aqueous-deficient dry eyes.

• Limiting the use of ointments to the evening or at bedtime

avoids the visual effects.

• Ointment preparations generally are non-irritating to ocular

tissue

• Preservative-free ointments are available.

 Tear Conservation: Occlusion of the
tear drainage system
• Occlusion of the lacrimal puncta or canaliculi prevents the
drainage of natural and artificial tears and is currently the
most common nonpharmacological therapy for dry eye
disease.

Benefits:
• Improve the quantity and the quality of the aqueous
component of the tear film,
• Relieving symptoms and signs of dry eye,
• making patients more comfortable and
• reducing the need for artificial tears
Calonge, M., (2001)
 Tear Conservation: Occlusion of the
tear drainage system
Punctal plugs

Calonge, M., (2001)

 Treatment: Tear Stimulation
• Parasympathetic cholinergic nerves are primarily responsible
for tear secretion, and acetylcholine (M3) receptors are
present on secretory epithelia of lacrimal glands and on
mucin-producing goblet cells in the conjunctiva.

• Pilocarpine (SalagenTM) is a parasympathomimetic agent with

a muscarinic secretory effect.

• Only if lacrimal gland remain functional.

• Side effects: nausea, sweating, abdominal cramps.

Treatment: Anti-inflammatory

Cyclosporine A

Corticosteroids
 Anti-inflammatory: Cyclosporine
• Cyclosporine A (CsA) is useful in the management of
moderate to severe dry eye disease.

It is used for the treatment of

• Autoimmune disease
• It is also used for the treatment of ocular manifestations
caused by autoimmune disease
• Endogenous uveitis.
• To prevent rejection after tissue/organ transplantation
 Anti-inflammatory: Cyclosporine
A decrease in inflammation is due to:

• Inhibition of T-cell lymphocytes and the production of

interleukin 2 (IL-2).

• Reduction of the ocular surface epithelial integrity and

sensitivity.

• Increasing the neural signals to the lacrimal glands by

enhanced ocular sensitivity
 Anti-inflammatory: Corticosteroids
• Studies have shown unpreserved topical corticosteroids (i.e.,
methylprednisone or loteprednol etabonate) can improve the
severity of symptoms and decrease levels of ocular surface
inflammation and cytokines.

• However, they can have potential unwanted side effects such

as ocular hypertension, glaucoma, cataracts, and secondary
infections.

• Therefore topical corticosteroid use in dry eye should be

limited to short periods (less than 2 weeks) and for
symptoms that are severe and refractory to other treatments.
 Anti-inflammatory: Tetracycline
• Tetracycline is a class of antibiotic that has anti-inflammatory
prosperities.

• Systemic doxycycline has been reported to improve irritation

symptoms, increase tear film stability and decrease the severity
of ocular surface disease

• It is recommended for patients with dry eyes with significant

component of Meibomian gland disease.

• Side effects: increase skin photosensitivity and gastrointestinal

complaints
 Treatment: Hormonal Therapy
• Androgenic steroids may have beneficial effect for the ocular
manifestations of Sjogren’s syndrome.

• Androgenic hormones such as testosterone appear to

attenuate autoimmune reactions.

• Androgen has immunosuppressive effects on the lacrimal

glands.
 Treatment: Hormonal Therapy
• Women with primary and secondary Sjogren’s syndrome have
been found to be androgen deficient

• Estrogens have been implicated in the pathogenesis and

progression of many autoimmune disorders and dry eyes.

• Hormone replacement therapy in postmenopausal women is

associated with a significant increase in the prevalence of dry
eye symptoms
 Omega-3 Fatty Acids
• Tears contain essential fatty acids such as omega-3 and
omega-6 which are obtained through diet.
• They are present in: Flaxseed, blackcurrant seed, canola oil,
walnuts, soy and cold water fish, tuna, salmon, sardines.

• A higher ratio of omega-6 to omega-3 fatty acid may decrease

incidence of dry eye syndrome
Thank you