Dry eye disease, also known as keratoconjunctivitis sicca, is a condition caused by disturbances in the tear film that leads to an unstable tear film when the eye is open. It is a common reason for visits to ophthalmologists and affects about 75% of people over age 65, with the average patient being 54 years old. The disease involves inflammation that disrupts the normal feedback loop controlling tear production. Diagnosis involves tests like tear breakup time and Schirmer tests, and treatment focuses on replacing tears through artificial drops or increasing natural tear production through drugs like cyclosporine drops.
2. What is Dry Eye Disease?
Disease of ocular surface caused by
disturbances of natural function and
protection of external eye leading to an
unstable tear film when eye is open
3. Prevalence of Dry Eye Disease
Average age of a dry eye patient is 54;
most are women.
Dry Eye Syndrome affects 75% of
people over age 65.
Common reason for ophthalmologist
visits.
4.
5. Normal tearing
depends on a
neuronal feedback
loop
Secretomotor
Nerve Impulses
Lacrimal
Glands Tears Support and Maintain
Ocular Surface
Ocular Surface
Neural Stimulation
6. Inflammation disrupt
normal neuronal
Lacrimal Glands:
control of tearing.
• Neurogenic Interrupted Secretomotor
Inflammation Nerve Impulses
• T-cell Activation
• Cytokine
Secretion into
Tears
Tears Inflame Ocular Surface
Cytokines
Disrupt Neural Arc
7. A complex mixture of
proteins, mucin, and
electrolytes
Antimicrobial proteins:
Lysozyme, lactofer rin
Growth factors &
suppressor s of
inflammation: EGF, IL-1RA
Soluble mucin 5AC
secreted by goblet cells
for viscosity
Electrolytes for proper
osmolarity
8. Decrease in many proteins
Decreased growth factor
concentrations
Altered cytokine balance
promotes inflammation
Soluble mucin -5AC g reatly
decreased
Due to goblet cell loss
Impacts viscosity of
tear film
Pr oteases activated
Increased electrolytes
10. AQUEOUS TEAR DEFICIENCY:
also known as KCS
seen in 1.congenital alacramia
2.paralytic hyposecretion
3.1˚& 2˚ sjogrens disease
4.Riley day syndrome
5.Idiopathic
• MUCIN DEFICIENCY: occurs when goblet cells
damaged
1.hypovitaminosis A
2.trachoma
3.chemical burns & radiations
4.ocular pemphigoid, SJS
11. LIPID DEFICIENCY:
Rare phenomena
Congenital anhydrotic ectodermal dysplasia with
absence of meibomian glands
Chronic blepharitis and chronic meibomitis
IMPAIRED EYELID FUNCTION:
.Bells palsy .Lagophthalmus
.Exposure keratitis .ectropion
.Dellen
.Sympblepheron
13. Medications T hat May
Contribute
to Dr y Eye Disease
Systemic
Antihyper tensives • Topical
Antiandr ogens – Preservatives in
Anticholiner gics Tears
Antidepr essants
Antiar rhythmic
Dr ugs
Par kinson’s Disease
Agents
Antihistamines
14. SYMPTOMS
Ir ritation
For eign body sensation
Itching
Non specific ocular
discomfor t
Chr onicall y sor e eyes
not responding to variety
of dr ops instilled
15. SIGNS
String y mucus and par ticulate
matter in tear film
Lustureless ocular surface
Conjunctival xer osis
Cor neal changes - punctate epithelial
er osions and filaments
16. Patient Types with High
Incidence of Dr y Eye
Disease
Women aged 50 or older
Women using
postmenopausal hor mone
replacement therapy
T hose with ocular
comorbidities
Contact lens wearer s
Smoker s
1
Schaumberg et al. Am J Ophthalmol. 2003;
2
Schaumberg et al. JAMA. 2001;
3
Lemp. CLAO J. 1995;
4
Multi-Sponsor Surveys, Inc. The 2005 Gallup Study of Dry Eye Sufferers. 2005.
17. DRY EYE
SYNDROMES
XEROSIS(XEROPHTHALMIA)
Dry lustureless condition of conjunctiva due to
deficiency of mucin
LOCAL OCULAR GENERAL DISEASE
AFFECTION
a) Trachoma , burns, Deficiency of vitamin A
pemphigoid, diphtheria
Cicatricial degeneration Occurrence of bitots
of conjunctival spots
epithelium
b) Ectropion or proptosis
18. KERATOCONJUNCTIVITIS SICCA:
deficiency of aqueous component of
tear s i.e lacrimal tear s
primar y
secondar y
kcs & xer ostomia kcs & rheumatoid
ar thritis
Pathologically focal accumulation &
infiltr ation with l ymphocytes & plasma
cells
Tear lysozyme r atio of 0.1 -> KCS
19. DIAGNOSIS
1.TEAR FILM BREAK UP TIME(BUT):
interval between complete blink & appearance of first
randomly distributed dry spot on cornea
After instilling drops of fluorescein dye, examintion
under SLE is carried out with cobalt blue light
NORMAL – 15 -35 SECONDS
<10 SECS- UNSTABLE TEAR FILM
BUT- an indicator of adequacy of mucin component
20. Schirmer Test: 5 * 35 mm strip of
w hatman 41 filter
paper folded 5mm
fr m one end kept
in lower for nix at
jn of lateral 1/3 rd &
medial 2/3 rd
NORMAL
>15mm
MILD TO MODERATE
KCS 5-10
mm
23. 4. Restasis ™
Ophthalmic emulsion of cyclosporine
0.05%.
Prescription therapy for dry eye disease.
Restasis™ is FDA approved to increase tear production
in patients whose tear production may be reduced
by inflammation of the eye associated with
keratoconjunctivitis sicca.
24. 5.PRESERVATION OF EXISTING
TEARS
BY REDUCING DECREASING
EVAPORATION DRAINAGE:
1. Room temperature 1.Collagen implants
2. Moist chambers 2.Electrocauterisation
3. Protective glasses 3.Cyanoacrylate tissue
adhesives
4.Argon laser & surgical
occlusions.
Notas del editor
Dry eye disease Results from localized immune-mediated inflammation that ultimately affects the entire ocular surface/lacrimal gland/neural feedback functional unit. The main and accessory lacrimal glands: Susceptible to inflammation due to decreased neural or androgen support. Activation of lymphocytes leads to T-cell-mediated inflammation, cytokine production, the presence of cytokines in tears, and acinar cell apoptosis. The ocular surface: Cytokines in tears trigger inflammation (T-cell and epithelial cell activation, leukocyte recruitment) on the ocular surface, disrupt epithelial cell function, interfere with mucin production. Irritation can also trigger chemically mediated inflammation leading to activation of trafficking lymphocytes (T cells). The neural feedback loop: Sensory activity on the ocular surface is disrupted by pro-inflammatory cytokines and compromised epithelial cells, impacting afferent signaling. Sensory input to the lacrimal glands is decreased by disruption of the neuronal loop and by the direct inhibitory effect of inflammatory cytokines in the glands on secretomotor nerve endings. Dysfunction in any one element can lead to dysfunction in all elements, with subsequent development of chronic inflammation and dry eye disease. Inadequate tear production, altered tear composition, or secretion of inflammatory substances into tears can result in ocular surface inflammation. Stern et al, Cornea. 1998;17:584; Nelson et al, Adv Ther. 2000:17:84.
To understand dry eye disease as a disorder of the tear film, we need to appreciate the components of tears and their functions in the normal, healthy tear film. Normal, healthy tears contain, in addition to water, a complex mixture of proteins, mucins, and electrolytes. The most abundant proteins have antimicrobial functions: lysozyme and lactoferrin. Immunoglobulins, such as IgA, IgG, and IgM, also have protective functions. Cells are constantly sloughed off and lost from the most superficial layer of ocular epithelia. Growth factors are very small proteins that regulate the process for replacement of epithelial cells and are necessary for wound healing. Many growth factors are present in tears, including epidermal growth factor (EGF), as shown here. Mucins are critical for the viscosity of the tear film. The soluble mucin (mucin 5AC) is secreted by conjunctival goblet cells, whereas membrane-bound mucins originate from the epithelial cells they are bound to. The electrolyte concentrations in healthy tears are maintained in the proper ranges to ensure correct osmolarity, which is important for many aspects of epithelial and nerve cell function. Reference Stern ME, Beuerman RW, Pflugfelder SP. The normal tear film and ocular surface. In: Pflugfelder SP, Beuerman RW, Stern ME, eds. Dry Eye and Ocular Surface Disorders . New York, NY: Marcel Dekker; 2004:41-62.
Now let’s look at the abnormal composition of tears that are characteristic of chronic dry eye. The concentrations of many tear proteins, including those with antimicrobial functions, are reduced. Growth factor concentrations are reduced as well. The soluble mucin 5AC is greatly reduced in concentration because of the profound loss of goblet cells from the conjunctival epithelium that is typical of chronic dry eye. This impacts the viscosity of the tear film. Proteases, which are normally latent and inactivated in healthy tears, become activated. They can degrade the extracellular matrix and the tight junctions between adjacent cells of the corneal epithelium. Activated proteases are also responsible for cleavage of many cytokines into an activated pro-inflammatory form. The concentration of electrolytes increases, meaning that the osmolarity of the tear film is increased in chronic dry eye. References Solomon A, Dursun D, Liu Z, Xie Y, Macri A, Pflugfelder SC. Pro- and anti-inflammatory forms of interleukin-1 in the tear fluid and conjunctiva of patients with dry-eye disease. Invest Ophthalmol Vis Sci. 2001;42:2283-2292. Zhao H, Jumblatt JE, Wood TO, Jumblatt MM. Quantification of MUC5AC protein in human tears. Cornea. 2001;20:873-877. Ogasawara K, Mitsubayashi K, Tsuru T, Karube I. Electrical conductivity of tear fluid in healthy persons and keratoconjunctivitis sicca patients measured by a flexible conductimetric sensor. Graefes Arch Clin Exp Ophthalmol. 1996;234:542-546.
The prevalence of dry eye increases with age, particularly for women age 50 or older, and among postmenopausal women using hormone replacement therapy. This association with postmenopausal status is consistent with the known role of androgens in stimulation of the lacrimal and meibomian glands, which help maintain a normal tear film. Androgen levels naturally decline after menopause. Ocular comorbidities such as graft-versus-host disease, xerophthalmia, cicatricial pemphigoid, atopic keratoconjunctivitis, and ocular rosacea are also associated with increased risk of dry eye disease. Smokers are also at risk, perhaps due to repeated irritation of the ocular surface by smoke. Patients who feel the need to use artificial tears 3 or more times per day should always be evaluated further for dry eye disease. References Schaumberg DA, Sullivan DA, Buring JE, Dana MR. Prevalence of dry eye syndrome among US women. Am J Ophthalmol. 2003;136:318-326. Schaumberg DA, Buring JE, Sullivan DA, Dana MR. Hormone replacement therapy and dry eye syndrome. JAMA. 2001;286:2114-2119. Lemp MA. Report of the National Eye Institute/industry workshop on clinical trials in dry eyes. CLAO J. 1995;21:221-232. Multi-Sponsor Surveys, Inc. The 2005 Gallup Study of Dry Eye Sufferers; Princeton, NJ: 2004.
The Schirmer test (minus anesthesia) measures reflex tear secretion “ Schirmer I” With anesthesia (“Schirmer II”), eliminates stimulated tearing Stimulated tearing can occur because of introduction of the filter paper strip Measures so-called “basal” tearing A filter paper strip is introduced to the lower lid of the eye. Dry eye is indicated if less than 10 mm of the strip becomes wet with tears after 5 minutes of exposure. Lemp, CLAO J. 1995;21:221-232.
What Is Restasis ™ ? Emulsion of cyclosporine 0.05% for human ocular use Unique emulsion technology allows a low concentration of cyclosporine to be effective Cyclosporine is an immunomodulator with anti-inflammatory effects Low concentrations of cyclosporine are effective Specifically targets an underlying pathology of dry eye disease, immune-mediated inflammation, by inhibiting T-cell activation