Dry Eye

Makmur Sejati
I1011141078
Physiology 1. The tear film has three layers
Lipid layer secreted by the
meibomian glands.
Aqueous layer secreted by the
lacrimal glands.
Mucous layer secreted
principally by conjunctival
goblet cells.
2. Spread of the tear film
 The tear film is mechanically
distributed over the ocular
surface through a neuronally
controlled blinking mechanism.
 Three factors are required for
effective resurfacing of the tear
film:
 Normal blink reflex.
 Contact between the external
ocular surface and the eyelids.
 Normal corneal epithelium.
Definition
“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
neurosensoryabnormalities play etiological roles.”
 Classification
 AQUEOUS-DEFICIENT DRY EYE (ADDE)
Sjogren Syndrome Dry Eye (SSDE)
associated systemic diseases
 Rheumatoid arthritis
 Polyarteritis nodosa
 Systemic lupus erythematosis
 Wegener granulomatosis
 Systemic sclerosis
 Primary biliary cirrhosis
 Mixed connective tissue disease
 Classification (1)
 AQUEOUS-DEFICIENT DRY EYE (ADDE)
Non- Sjogren Syndrome Dry Eye (NSDE)
 Intrinsic Lacrimal Gland Deficiency ( Lacrimal gland ablation, Congenital
alacrima, and Triple A syndrome)
 Age-related ADDE dry eye
 Inflammatory and Other Lacrimal Gland infiltration (Sarcoidosis, Lymphoma,
Viral Infection and Radiation Injury)
 Lacrimal Gland Obstruction ( Cicatricial Conjunctivitis, GVHD, Stevens-
Johnson Syndrome/TEN, Mucous Membrane Pemphigoid, Cicatricial
pemphigoid, Pemphigus, Trachoma and Chemical injury
 Hyposecretory States e Failure of the Lacrimal Functional Unit ( Reflex
Afferent Block and Secretomotor Block)
Classification (2)
 EVAPORATIVE DRY EYE
Intrinsic EDE
 Age-related meibomian gland changes
 The influence of sex hormones on meibomian gland function
 Meibomian gland dysfunction
 Disorders of lid aperture, congruity and dynamics
Extrinsic EDE
 Vitamin A deficiency
 Topical drugs
 Contact Lens Wear
 Ocular Surface Disease
Aqueous-deficient
Sjogren Syndrome Dry Eye
 Sjogren syndrome is a chronic autoimmune disorder
characterized by immune cell infiltration of exocrine
glands (exocrinopathy or epitheliitis) and systemic
complications due to autoantibody production, immune
complex deposition and lymphocytic infiltration of many
organs
Sjogren Syndrome Dry Eye (1)
 There are two forms of SS,
 Primary SS consists of the occurrence of ADDE in combination with
symptoms of dry mouth, in the presence of autoantibodies, evidence
of reduced salivary secretion.
 Secondary SS consists of the features of primary SS together with
the features of an overt autoimmune connective disease, such as
rheumatoid arthritis, systemic lupus erythematosis, polyarteritis
nodosa, Wegener.s granulomatosis, systemic sclerosis, primary
biliary sclerosis, or mixed connective tissue disease.
Non-Sjogren Syndrome Dry Eye
Intrinsic Lacrimal Gland Deficiency
 Lacrimal gland ablation. DED may be caused by ablation of the lacrimal
gland at any age, or by severance of the ducts during lid surgery. DED is not
an inevitable outcome, since the accessory glands and conjunctival
secretions may compensate in some cases.
 Congenital alacrima. Congenital alacrima or lacrimal agenesis may occur as
an inherited disorder sometimes with agenesis of the salivary glands and is a
rare cause of DED inyouth or infancy. Additional associations are with
blepharophimosis , lacrimal-auriculo-dental-digital syndrome (LADD),
Pierre-Robin sequence and Allgrove
 Triple A-syndrome. Triple A- or Allgrove syndrome, is a progressive,
recessively inherited disorder, in which congenital alacrima is associated
with achalasia of the cardia, Addisons disease, central neurodegeneration
and autonomic dysfunction. It is caused by mutations in the AAAS gene,
encoding the protein ALADIN.
Non-Sjogren Syndrome Dry Eye (1)
 Age-related Non-Sjogren Syndrome dry eye
 The most common form of NSDE is age-related ADDE and corresponds to
the term keratoconjunctivitis sicca (KCS). The clinical features resemble
those of SSDE, but, in general, age of onset is later, the degree of lacrimal
gland infiltration lower, the rate of progression slower and severe disease
less common than in SSDE.
 The potential contributions of tissue aging to this disorder have been
reviewed by Rocha et al. , who point out that the reported fall in reflex
Schirmer values over the life span could be due to a failure of any of the
elements that go to make up the lacrimal functional unit and therefore to any
one of a combination of factors such as a loss of sensory drive from the
ocular surface, a reduced delivery of secretory neururotransmitters, as well
as the loss of functional secretory tissue.
Non-Sjogren Syndrome Dry Eye (2)
 Inflammatory and other infiltrations of the lacrimal glands
 Sarcoidosis. Sarcoidosis is a chronic systemic disorder of unknown origin
with an estimated prevalence ranging from 1 to 40 cases per 100,000
population. It is characterized by the presence of non-caseating granulomas
in multiple organs with the lungs being involved most frequently. Patients
with lacrimal gland involvement (up to 63% of the cases) typically show
significant enlargement of the gland.
 Lymphoma. Infiltration of the lacrimal gland by lymphomatous cells may
cause DED
 Viral infection (Hepatitis C, HIV e AIDS,
 Radiation injury. DED may be a complication of radiotherapy for benign
and malignant conditions of the orbit, or of the head and neck, if the
periorbital area is included within the treatment field.
Non-Sjogren Syndrome Dry Eye (3)
Lacrimal gland obstruction
 DED can be a serious outcome in those diseases causing extensive
conjunctival scarring, such as chronic graft-versus-host disease
(GVHD), Syndrome (SJS)/toxic epidermal necrosis (TEN), mucous
membrane pemphigoid and trachoma and also after physical and
chemical injury.
 Trachoma. Trachoma is a chronic, scarring keratoconjunctivitis initiated
by recurrent infections with Chlamydia trachomatis in childhood. The
scarring complications, which are a cause of blindness on a global scale,
usually occur in adulthood and include corneal opacity resulting from
tarsal and conjunctival scarring, limbal stem cell deficiency, and
trichiasis. DED is part of the overall picture, resulting from lacrimal
gland duct obstruction, goblet cell loss, a cicatrizing meibomian gland
obstruction and lid malapposition
Non-Sjogren Syndrome Dry Eye (4)
 Hyposecretory states due to failure of the lacrimal functional unit
 Reflex afferent block .Tear production is under neural regulation and an alteration
in the trigeminal inputs from the cornea can cause DED by blocking lacrimal
protein, electrolyte andwater secretion. Corneal nerve terminals also exert a
number of trophic functions, which support epithelial cell proliferation and/or
migration and possibly immune regulation. A loss of sensory drive can come
about in several ways.
 Secretomotor blockade
 Parasympathetic damage. Damage to the parasympathetic innervation of the lacrimal
gland may follow injury to the nervus intermedius during surgery for vestibular
schwannomas in the cerebellopontine angle. An associated lagophthalmos due to injury
of the seventh cranial nerve may compound the resulting DED
 Pharmacological inhibition of lacrimal secretion. A large number of systemic
medications have been reported as risk factors for DED, including antidepressants,
anticholinergics, antipsychotics, antispasmotics and antihistamines as well as
chemotherapeutics, antihypertensive, anti-arrhythmics, antithyroid agents, opioid
analgesics.
Evaporative
Intrinsic EDE
 Age-related meibomian gland changes
 There is general agreement that meibomian gland acini are lost with increasing
age
 age-related decrease in number of acini and acinar diameter with age, together
with increased secretion reflectivity and acinar wall changes,
 The influence of sex hormones on meibomian gland function
 Meibomian function is strongly influenced by the sex hormones,
particularly androgens. In brief, androgens stimulate the synthesis and
secretion of lipids by the meibomian gland and suppress the expression of
genes related to keratinization. Conversely a deficiency of androgen action,
such as occurs in aging, Sjogren syndrome, antiandrogen treatment and
complete androgen insensitivity syndrome, is associated with MGD, altered
meibum lipid profiles and evidence of decreased tear film stability.
Intrinsic EDE (1)
Meibomian gland dysfunction
High meibum delivery state e meibomian seborrhea.
Low meibum delivery states - obstructive meibomian
gland dysfunction.
 Cicatricial MGD
 Non-cicatricial MGD.
 Tear volume in meibomian gland dysfunction.
 MGD secondary to systemic chemical exposure
 Anterior blepharitis-related MGD.
 Genetically determined meibomian gland diseases.
Intrinsic EDE (2)
 Disorders of lid aperture, congruity and dynamics
 Incomplete lid closure of some degree is not uncommon in normal subjects
during blinking. In normal subjects, increased ocular surface exposure and
evaporation occurs in upgaze
 Incomplete lid closure or lid deformity, leading to increased exposure or
poor tear film resurfacing, is accepted as a cause of ocular drying following
a VIIth cranial nerve palsy (lagophthalmos) or after surgery to the lids.
Extrinsic EDE
 Vitamin A Deciency
 Vitamin A deciency may cause dry eye (xerophthalmia) by two distinct mechanisms.
Vitamin A is essential for the development of goblet cells in mucous membranes and
the expression of glycocalyx mucins. These are deficient in xerophthalmia, leading to
an unstable tear film characterized by early tear film break up. Vitamin A deiciency
can cause lacrimal acinar damage, and, therefore, some patients with xerophthalmia
may have a lacrimal, aqueous tear-decient dry eye
 Topical Drugs
 Topical drugs may act at the level of the ocular surface through various
mechanisms, exerting allergic, toxic and/or immunoinflammatory
effects or by chemical interaction with the lacrimal film, either by
disrupting the lipid layer through detergent tensioactive effects, by
reducing aqueous secretion, or by damaging: goblet cells; the
conjunctival and corneal epithelia; corneal nerves through neurotoxic
effects; or even eyelids at the skin or meibomian gland level.
Extrinsic EDE
Extrinsic EDE
 Contact Lens Wear
 Contact lens wearers may experience ocular discomfort, frequently
interpreted as dryness, as well as variable degree of decreased corneal
sensation.
 Ocular Surface Disease
 There is evidence that various forms of chronic ocular surface disease result
in destabilization of the tear film and add a dry eye component to the ocular
surface disease.
 Investigation
1. Tear film break-up time
 The tear film BUT is abnormal in aqueous tear deficiency and meibomian
gland disorders. It is measured as follows:
 Fluorescein 2% or an impregnated fluorescein strip moistened with non-preserved
saline is instilled into the lower fornix.
 The patient is asked to blink several times.
 The tear film is examined at the slit lamp with a broad beam using the cobalt blue
filter. After an interval, black spots or lines appear in the fluorescein-stained film ,
indicating the formation of dry areas.
 The BUT is the interval between the last blink and the appearance of the first
randomly distributed dry spot. A BUT of less than 10 seconds is suspicious.
 The development of dry spots always in the same location may indicate a local corneal
surface abnormality (e.g. Epithelial basement membrane disease) rather than an intrinsic
instability of the tear film.
 Investigation (1)
2. Schirmer test
 The Schirmer test is a useful assessment of aqueous tear production. The test involves
measuring the amount of wetting of a special (no. 41 Whatman) filter paper, 5 mm
wide and 35 mm long. The test is performed as follows:
Excess tears are delicately dried. If topical anaesthesia is applied the excess should be
removed from the inferior fornix with filter paper.
The filter paper is folded 5 mm from one end and inserted at the junction of the middle
and outer third of the lower lid, taking care not to touch the cornea or lashes.
The patient is asked to keep the eyes gently closed.
After 5 minutes the filter paper is removed and the amount of wetting from the fold
measured.
Less than 10 mm of wetting after 5 minutes without anaesthesia or less than 6 mm with
anaesthesia is considered abnormal.
 Results can be variable and a single Schirmer test should not be used as the
sole criterion for diagnosing dry eye, but repeatedly abnormal tests are highly
supportive.
 Investigation (2)
3. Ocular surface staining
 Fluorescein where there is sufficient damage to allow the dye to enter the
tissues.
 Rose Bengal is a dye that has an affinity for dead or devitalized epithelial cells
that have a lost or altered mucous layer
 Lissamine green stains in a similar fashion to rose Bengal but causes less
irritation and may be preferred.
 The pattern of staining may aid diagnosis:
 Interpalpebral staining of the cornea and conjunctiva is common in aqueous tear
deficiency.
 Superior conjunctival stain may indicate superior limbic keratoconjunctivitis.
 Inferior corneal and conjunctival stain is often present in patients with blepharitis or
exposure.
Treatment
Tear substitutes
Drops and gels : cellulose derivates (hypromellose,
methylcellulose), carbomer gels, polyvinyl alcohol, diquafosol
Ointments
Paraffin, used at bedtime to supplement daytime
Eyelid sprays
Stabilize the tear film and reduce evaporation
Artificial tear insert
Emplaced once or twice daily
Mucolytic agents
Useful in patients with corneal filaments & mucous plaque
Treatment (1)
Anti-inflammatory agents
Topical steroids
 Supplement for acute exacerbation
Omega fatty acid supplement
 Reduction of topical medication
Oral tetracyclines
 Control associated belpharitis, meibomianitis, reduce tear level of
infl. mediator
Topical ciclosporin
 Reduces T-cell mediated infl. of lacrimal tissue, increase the
number of goblet cell
Treatment (2)
Optimization of environmental humidity
Reduction of room temperature
 Minimize evaporation of tears
Room humidifiers
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