Download Management of Dry Eye

ManagementCornea
Protocols
Management Protocols:
Management of Dry Eye
Neelima Aron
MD
Neelima Aron MD, Deepali Singhal MBBS, Rajesh Sinha MD
Dr. Rajendra Prasad Centre for Ophthalmic Sciences,
All India Institute of Medical Sciences, New Delhi
D
ry eye is defined as ‘‘a multifactorial disease of the
tears and ocular surface that results in symptoms of
discomfort, visual disturbance, and tear film instability with
potential damage to the ocular surface, accompanied by
increased osmolarity of the tear film and inflammation of
the ocular surface1.”
Dry eye, alone or in combination with other conditions,
is a frequent cause of ocular irritation that leads patients
to seek ophthalmologic care. While these symptoms often
improve with treatment, the disease usually is not curable,
which may be a source of patient and physician frustration.
Dry eye is a cause of visual morbidity and may compromise
results of corneal, cataract and refractive surgery.
with rosacea, seborrhea); Hands (joint deformities
characteristic of rheumatoid arthritis, Raynaud
phenomenon, splinter haemorrhage underneath
nails).
• Slit-lamp biomicroscopy: It should focus on the
following examination:
• Tear film: height of the meniscus, debris, increased
viscosity, mucus strands
• Anterior
and
posterior
eyelid
abnormalities of meibomian glands
• Puncta (patency, position, presence, and position
of plugs)
Diagnosis
•
The appropriate management of dry eye disease depends
on identifying the etiology of the same by a step wise
approach.
• Bulbar conjunctiva (e.g., punctate staining with
rose bengal, lissamine green, or fluorescein dyes;
hyperemia; localized drying; keratinization,
chemosis)
• Cornea (localized interpalpebral drying, punctate
epithelial erosions, punctate staining with rose
Bengal or fluorescein dyes, filaments, epithelial
defects.
History
Several questionnaires may be useful in completing the
patient history, including the Ocular Surface Disease Index,
the Dry Eye Questionnaire, and the Impact of Dry Eye on
Everyday Life questionnaire.
Examination
All patients with dry eye symptoms should undergo a
comprehensive external eye and systemic evaluation. It
includes the following:
• Visual acuity
• External examination
•
Eyelids/eyelashes/Adnexa; Proptosis; Cranial nerve
function (e.g., cranial nerve V, cranial nerve VII);
Skin (e.g., scleroderma, facial changes consistent
margins:
Inferior fornix and tarsal conjunctiva
Diagnostic Tests
The diagnostic tests ordered for possible systemic
underlying condition in a patient with dry eye is given in
Table 1,2.
The most commonly used diagnostic tests forinitial
assessment of dry eye have been ranked as tear break up
time (93%), corneal staining (85%), tear film assessment
(76%), conjunctival staining (74%), and the Schirmer test
(54%)2. These tests should be performed in this sequence
because the Schirmer test can disrupt tear film stability and
www. dosonline.org l 43
Management of Dry Eye
Figure 1: Major etiological causes of dry eye
cause false positive ocular dye staining.
Management
The dry eye severity grading was given by DEWS
based on ocular signs, symptoms and diagnostic tests
(Table 3). Management of dry eye depends on the severity
of the disease and the patient’s response to treatment
(Table 4). Treatment includes environmental modification,
topical lubricants, anti-inflammatory agents and surgical
management (Table 5).
a) Tear supplementation: Ideal lubricant should be
preservative free, contain electrolytes mainly potassium
and bicarbonate, should have a polymeric system
to increase retention time with neutral to slightly
alkaline pH, minimum blurring, delivers optimal visual
performance throughout the day, and should have the
ability to spread over the cornea quickly and efficiently.
It consists of demulcents, lipids and compatible solutes.
b) Tear retention:
(i) Punctal occlusion: Indicated in moderate to severe
dry eye not relieved on unpreserved artificial tears and
without any evidence of inflammation or infection. It
includes absorbable inserts and non-absorbable inserts.
44 l DOS Times - Vol. 20, No. 9 March, 2015
(ii) Moist chamber glasses: Decrease the ocular discomfort
associated with dry eye by reducing tear evaporation
and increasing humidity around the eye.
(iii) Contact lenses: Silicone rubber lenses and rigid
permeable scleral bearing hard lenses can be used.
They help to protect surface epithelium and minimize
frictional forces, improve comfort and promote healing
of persistant epithelial defects.
(iv) Tarsorraphy: Used in severe or refractory dry eyes
and helps by reducing the surface area of exposure in
pateints with severe epitheliopathy.
c) Tear stimulation:
(i) Secretagogues: Stimulate endogenous tear production.
It includes pilocarpine, cevilimine, eledosin, diquafosol
and rebapimide.
d) Tear substitution
(i) Autologous serum: Used in moderate to severe dry
eye. It is unpreserved and can be stored frozen for
3-6 months and has been reported to contain essential
components for epithelial healing such as EGF and
neurotrophic factors such as nerve growth factor ,
substance P and IGF-1.
Management Protocols
Table 1: Diagnostic tests for underlying systemic diseases
Suspected Underlying Condition
Diagnostic Testing
Sjogren syndrome
SSA, SSB, ANA, RF
Thyroid eye disease
Anti-thyroid peroxidase antibody, antithyroglobulin antibody, B-scan sonogram to
assess extraocular muscle thickness
Sarcoidosis
Serum lysozyme, ACE, chest CT to determine extent of disease (consult with a
pulmonologist as necessary), conjunctival biopsy
Cicatricial pemphigoid
Conjunctival biopsy with light microscopic as well as immunofluorescent or
immunohistochemical studies.
ACE=Angiotensin-converting enzyme; ANA=Antinuclear antibody; RF=Rheumatoid factor; SSA=Anti-Sjogren
syndrome A antibody (anti-Ro); SSB= Anti-Sjogren syndrome B antibody (anti-La)
Table 2: Characteristic findings for Dry eye syndrome Diagnostic testing
Aqueous tear deficiency
Test
Characteristic Findings
Ocular surface dye staining
Pattern of exposure zone (interpalpebral) corneal
and bulbar conjunctival staining typical
Tear break up time
Less than 10 seconds considered abnormal
Aqueous tear production (Schirmer’s 10 mmm or less for schirmer test with anesthesia
test)
considered abnormal
Evaporative tear
deficiency
Lacrimal gland function
Decreased tear lactoferrin concentrations
Tear osmolarity
Possibly increased with nuclear clinical implications
Ocular surface dye staining
Staining of inferior corneal and bulbar conjunctiva
typical
Tear break-up time
Less than 10 seconds considered abnormal
Tear osmolarity
Possibly increased with nuclear clinical implications
(ii) Salivary gland autotransplantation
Submandibular or minor salivary gland transplant can
be done in end stage DED with absolute aqueous tear
deficiency ( Schirmer test <1mm) with severe pain despite
of punctal occlusion and lubricants.
e) Anti-inflammatory therapy
(i) Cyclosporin: It is a fungal derived peptide and a
calcineurin inhibitor. It acts by reduction in pro
inflammatory cytokines (IL-6), inflammatory and
apoptotic markers and increases conjunctival goblet
cells.
(ii) Corticosteroids: Useful for their anti inflammatory
and immunomodulatory action causing supression
of lymphocyte proliferation and migration. They are
mainly used as a pulse therapy to control exacerbations.
(iii) Tetracyclines: They have anti - inflammatory,
antibacterial,
antiprotease,
antilipase
and
immunomodulatory actions. They are mainly used in
meibomian gland dysfunction.
(iv)Essential fatty acids: Omega-3 fatty acids play an
important role in the synthesis of meibum which forms
the lipid layer of tear film. They help in clearing and
thinning of meibomian gland secretions which in turn
improves symptoms of dry eye.
f) Newer modalities:
1. Topical vitamin A: Retinol is present in tears, and the
lacrimal gland seems to be its major provider to the
ocular surface epithelium. It can reverse conjunctival
squamous metaplasia and keratinization in severe DED
(cicatrizing conjunctivitis and GVH disease)3.
2. Interleukin- 17 receptor inhibitors: IL-17 has been
found associated with ocular inflammatory diseases
like uveitis, scleritis and dry eye syndrome. It has
been found that tear IL 17 levels are likely to correlate
clinically with corneal disease severity only in patients
with systemic inflammatory disease4.
3. Janus kinase inhibitors: Tofacitinib (CP-690,550): It
is under phase 1/2 trial and demonstrated a trend for
improving both signs and symptoms of dry eye5.
4. Anti lymphangiogenic agents: It has been shown that
low grade inflammation associated with DED is an
inducer of lymphangiogenesis without accompanying
www. dosonline.org l 45
Management of Dry Eye
Table 3: Dry eye severity grading system (DEWS)
Dry Eye Severity Grading Scheme
Dry Eye Severity Level 1
2
3
4*
Discomfort, severity
and frequency
Mild and/or episodic;
occurs under
environmental stress
Moderate episodic or
chronic stress or no
stress
Severe, frequent of
constant without
stress
Severe and/or
disabling and constant
Visual symptoms
None or episodic
mild fatigue
Annoying and/
or activity limiting
episodic
Annoying, chronic
and/or constant,
limiting activity
Constant and/or
possibly disabling
Conjunctival injection None to mild
None to mild
+/-
+/-**
Conjunctival staining
None to mild
Variable
Moderate to marked
Marked
Corneal staining
(Severity/Location)
None to mild
Variable
Marked Central
Severe punctate
erosions
Corneal/tear signs
None to mild
Mild debris, e
meniscus
Filamentary keratitis,
mucus, clumping, e
tear debris, ulceration
Lid/meibomian glands Meibomian gland
disease (MCD)
variably present
MGD variably present Frequent
Trichiasis,
keratinization,
symblepharon
Tear film break-up
time
Variable
< 10 seconds
< 5 seconds
immediate
Schirmer score (per
five min.)
Variable
< 10mm
< 5mm
< 2 mm
* Must have signs and symptoms
Table 4: Treatment recommendations for Dry eye syndrome by disease severity level
Mild
* Education and environmental modifications
* Elimination of offending topical or systemic medications
* Aqueous enhancement using artificial tear substitute, gels/ointments
* Eyelid therapy (warm compresses and eyelid scrubs)
* Treatment of contributing ocular factors such as blepharitis or meilbomianitis
* Correction of eyelid abnormalities
Moderate
In addition to above treatments:
* Anti-inflammatory agents (topical cyclosporine and corticosteroids), systemic omega-3 fally acids supplements
* Punctal plugs
* Spectacle side shields and moisture chambers
Severe
In addition to above treatments:
* Systemic anti-inflammatory agents
* Mucolytic agents
* Autologous serum tears
* Contact lenses
* Permanent punctal occclusion
* Tarsorrhaphy
46 l DOS Times - Vol. 20, No. 9 March, 2015
Management Protocols
Table 5: Categories of Dry eye treatment
Type of Therapy
Treatment
Environmental/Exogenous
Education and environmental modifications (e.g., humdifier)
Elimination of offending topical or systemic medications
Topical Medication
Antificial tear substitutes, gets ointments
Anti inflammatory agents (topical cyclosporine and corticosteroids)
Mucolytic agents
Autologous serum tears
Systemic medication
Omega-3 fatty acids (may increase prostate cancer risk in males)
Teracyclines (meibemian gland dysluction, rosacea)
Seretagagues
Surgical
Punctal plugs
Permanent punctual occlusion
Tarsorrhaphy
Repair of eyelid malpositions or exposure
Muccus membrane, salivary gland, amniotic membrane transplantation
Others
Eyelid therapy (warm compresses and eyelid hygiene)
Contact lenses
Moisture chamber spectacles
6. Sex hormone replacement therapy: Removal of
ovarian sex hormones accelerated the effects of dry
eye and caused increased lymphocytic infiltration and
apoptosis in animal models thus forming the basis of
replacement therapy as a treatment modality.
7. siRNAs: Can inhibit the transient receptor potential
vaniloid (TRPV1) gene expression using RNA
interference leading to decrease in ocular pain,
discomfort and altered sensitivity of cornea following
refractive surgery, dry eye and Sjogren’s syndrome.
In conclusion, as our understanding of the pathology
of dry eye disease improves, we will be able to develop
new strategies to treat the condition. As dry eye disease is
now regarded as a local immune-mediated inflammatory
condition, treatments aimed at treating this aspect are
especially promising.
References
Figure 2: National Eye Institute staging for dry eye
hemangiogenesis. Anti VEGF agents have shown to
reduce DED when injected intraperitoneally in murine
models6.
5. Lacritin and tear proteome: Lacritin is a tear proteins
selectively deficient in dry eye and can be used as a
natural replacement therapy7.
1. Lemp MA. The definition and classification of dry eye disease:
Report of the Definition and Classification Sub- committee of the
International Dry Eye WorkShop. Ocul Surf 2007;5:75--92.
2. Serin D, Karsloglu S, Kyan A, et al. A simple approach to the
repeatability of the schirmer test without anesthesia: eyes open or
closed? Cornea 2007;26:903-6.
3. Murphy PT, Sivakumaran M, Fahy G, Hutchinson RM: Successful
use of topical retinoic acid in severe dry eye due to chronic graftversus-host disease. Bone Marrow Transplant 18:641–2, 1996.
4. Kang et al. interleukin-17 in various ocular surface inflammatory
diseases. J Korean Med Sci. 2011; 26(7); 938-944.
5. Liew et al. Tofacitinib (CP-690,550), a Janus kinase inhibitor for dry
eye disease. Ophthalmology. 2012;119(7):1328-35.
6. Goyal et al. Blockade of prolymphangiogenic vascular endothelial
growth factor C in dry eye disease. Arch Ophthalmol. 2012; 130(1):
84–89.
7. Karnati R, Laurie DE, Laurie GW. Lacritin and the tear proteome as
natural replacement therapy for dry eye. Exp Eye Res. 2013;117:3952.
www. dosonline.org l 47