Dry eye disease : A review of diagnostic approaches andTreatments

Saudi journal of ophthalmology (2014)28,173-181Hui Lin,MD,PhD;Samuel C.Yiu,MD,PhDPresented By – Dr. Dildar Singh

Moderator - Dr. K.Kanthamani

“Dry eye is 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. It is accompanied by increased osmolarity of the tear film and inflammation of the ocular surface”.

Dry eye is a disturbance of the lacrimal functional unit, an integrated system that comprises of lacrimal glands, ocular surfaces (conjunctiva, cornea, meibomian glands), lids and sensory & motor nerves that connect them.

1. Irritation

2. Redness

3. Burning/ Stinging

4. Itchy eyes

5. Foreign body sensation

6. Blurred vision

7. Tearing

8. Contact lens intolerance.

9. Increased frequency of blinking

10. Mucous discharge.

11. Photophobia

SYMPTOMS

1. Chronic meibomitis

2. Blepharitis

3. Debris in tear film

4. Chronic papillary conjunctivitis

5. Tear marginal meniscus < 0.3 mm

6. Interpalpebral hyperemia

7. Gland orifice metaplasia

SIGNS

- Although both ADDE and EDE present with similar signs of reduced stability and increased tear film osmolarity.

- ADDE chiefly refers to a failure of lacrimal secretion and EDE is due to excessive water loss from the exposed ocular surface in the presence of normal lacrimal secretory function.

Diagnostic assessment

An ideal diagnostic method should be preferably non-invasive, objective, specific, reproducible and sustainable in terms of cost and time.

a) Subjective evaluation

b) Objective evaluation

Subjective evaluation :

• The symptoms and history of DE patients vary widely; therefore, validated questionnaires have been developed to ensure consistency in recording symptomatic information.

• Previously it was believed that DE can be diagnosed largely on the basis of symptoms; however, recent studies have questioned this opinion as there is often a lack of correlation between the severity of the symptoms and signs of DE.

Objective evaluation :

a) tear film assessment c) the Schirmer test as the most commonly used diagnostic tests for initial assessment of dry eye.d) Lacrimal river width e) Tear ferning testf) Lactoferrin contents g) Tear penetration pressure test

SCHIRMER TEST

SCHIRMER'S TEST I If wetting >10mm = normal eye If wetting <3mm = very severe dry eyeIf wetting 3-5 mm = severe dry eyeIf wetting 5-10mm = moderate dry eyeIf wetting is 10mm = mild dry eye SCHIRMER'S TEST IIIf Wetting<10mm -- >irratate the nasal mucosa with cotton bud & note the wetting after 2 min. If no Wetting or <1mm Sjogren's syndromeIf Wetting increases by 1mm Non-Sjogren's syndrome SCHIRMER'S TEST III – no diagnostic

LACRIMAL RIVER WIDTH TEAR FERN TEST

A drop of tear is collected from the lower meniscus and dropped onto a microscope slide and allowed to dry by evaporation.

Apart from these traditional clinical tests, we will discuss more about the less invasive evaluations based on the recently developed technologies related to :

a) tear hyperosmolarity b) tear film instability c) inflammation.

Tear osmolarity

• Increase in tear osmolarity is common to all types of DE

• Normal Osmolarity value 305 mOsms/l > 308 mOsms/l (mild DE) >312 mOsms/l (moderate to severe DE)

c) electrical conductivity or impedance

Tear film osmolarity can be measured in three ways:

Assessment of tear stability

• Tear break-up time (TBUT), introduced by Norn , remains the most frequently used diagnostic test to determine tear film instability.

• Non-invasive tear break-up time (NIBUT) involves the observation of an illuminated grid pattern reflected from the anterior tear surface.

NIBUT can be measured by: a) corneal topography b) interferometry c) aberrometry d) functional visual acuity assessment e) confocal microscopy

A) Topographical analysis systems

TEAR FILM TOPOGRAPHER

Uses :

• evaluate corneal surface regularity• tear film stability• evaluation of post-LASIK dry eye

B) Interferometry

LIPIVIEW INTERFEROMETER

• Coloured fringes that arise from interference between

light reflected from the surface of the lipid layer and from the interface between the lipid layer and the aqueous layer of the tear film.

• used to observe the nature, thickness and rupture of the lipid layer.

C) Aberrometry

WAVEFRONT ABERROMETER

• non-invasive assessment of the visual disturbances caused by higher order aberrations arising from tear film instability and break-up.

• Aberrometry could be utilized for not only detecting DE but also for monitoring the efficacy of treatments.

D) Functional visual acuity

• measure of visual acuity during sustained eye opening without blinking

• defined as the monocular recognition acuity at a specific time point

• decreases significantly in both non-Sjögren’s syndrome (NSS) and Sjögren’s syndrome (SS) dry eye patients

Optical coherence tomography

• Anterior segment OCT can measure the tear film thickness and tear meniscus parameters which indicate total tear volume.

• lower tear meniscus height and radius were the best indicators of DE with a cutoff meniscus height of 1.64 mm and radius of 1.82 mm.

E) Non Contact Confocal Microscopy

• non-contact, tandem-scanning confocal microscope demonstrating real-time images to observe the tear film.

Evaluation of ocular surface and

inflammation

Confocal microscopy

Meibomian gland evaluation

Corneal and conjunctival staining

Conjunctival impression cytology or brush cytology Other tests

• Corneal in vivo confocal microscopy (IVCM) is a novel, noninvasive, high-resolution tool that allows imaging the cornea at the cellular level and provides images comparable to histochemical methods and used for non- invasive impression cytology in DE evaluation.

1) Confocal Microscopy

• IVCM enables the study of:- a) corneal epithelium b) corneal stroma and keratocytes c) endothelial cells, d) corneal nerves e) corneal immune and inflammatory cells f) conjunctiva g) meibomian glands

• source of lipids in the lipid layer of the tear film

• MGD is the most common cause of evaporative dry eye• Meibomian glands can be assessed by :- a) slit lamp b) Meiboscopy c) Meibography d) Meibometry

2) Meibomian gland evaluation

• Invasive procedure which enables the assessment of ocular surface damage by instilling a dye:

a) sodium fluorescein b) rose bengal c) lissamine green

3) Corneal and conjunctival staining

• A vital dye which has no intrinsic toxicity.• Detects epithelial defects & irregularities.• Filter paper strips or 0.25% - 2% solution.• Sodium fluorescein emits green light(520nm) when

excited with with blue light (490nm).

Sodium fluorescein

Rose bengal

• Rose bengal is a vital stain taken up by dead and devitalised epithelial cells.

• Also stains mucous threads, filaments & strands .• Does not diffuse into the epithelial defects or penetrate

corneal stroma like fluorescein.• It is toxic resulting in decreased cell vitality, motility & cell

death.• Causes ocular discomfort –prior anaesthesia is needed.

Score 0 - absent Score 1-just present Score 2-moderate staining Score 3-gross staining

• Dark green, water soluble

• Degenerated cells, mucus, dead cells

• Less irritating

Lissamine green

• harvesting conjunctival epithelial,Goblet, and inflammatory cells from the bulbar mucosa

• cytokines IL-1a, mature IL-1b, and IL-1Ra are found in a significantly greater percentage of conjunctival cytology specimens from eyes with SS

• dry eye group was found to have a significant difference in the CD4/CD8 ratio

• Elevated matrix metalloproteinases levels in DE

4) Conjunctival impression cytology or brush cytology

Treatment

• Artificial tears provide palliative relief to eye irritation in patients with aqueous tear deficiency, but do not prevent the underlying inflammation

• Mild-to-moderate DE disease- Combinations of artificial tears, oral omega-3 essential fatty acid supplements, mucin secretagogues,short-term steroids, and daily cyclosporine A

Severe- autologous serum, oral tetracyclines, prosthetic lens, and systemic immunesuppressants

Severe forms associated with systemic diseases- surgical intervention, including tarsorrhaphy and amniotic membrane transplant.

Additionally, a stepwise guide to approach the best combination of medications to avoid symptoms of DE was also recommended

Anti-inflammatory treatments

Supplementary treatments

Surgical treatment

Anti-inflammatory treatments :

• Cyclosporine A Controls inflammation Increasing tear secretion Tear film stability Restoring epithelial damage Reducing disease recurrences

• Steroids Decreases inflammation (corticosteroids ) Apoptosis of lymphocytes

• Hormonal therapy (androgen and estrogen)

Increase tear production TBUT,lipid layer thickness.

• Antibiotics (azithromycin and tetracycline, doxycycline, and minocycline)

Decrease ocular surface inflammation,Normalize lipid production by the meibomian glands.

Supplementary treatments :

• Essential Fatty Acids (EFAs) Omega-3 FAs Anti-inflammatory Omega-6 FAs Proinflammatory.

Topical administration of resolvin E1, an omega-3 FA derivative increased tear production, helped maintain ocular surface integrity, decreased cyclooxygenase 2 expression and decreased immune cell infiltration in experimental dry eye.

• Nerve growth factor (NGF) Increase ocular surface sensitivity, Inhibit inflammatory reactions, Regulate tear film production, Reducing the apoptosis of corneal epithelial cells triggered by hyperosmolarity .• Autologous serum Autologous and umbilical cord serum contains substances that support the proliferation, differentiation, and maturation of the normal ocular surface epithelium and therefore, finds application in the treatment of severe DE.• Acupuncture

Surgical treatment

• Punctal occlusion Reduces drainage, preserves natural tears and prolongs the effect of lubricants.

• Salivary gland procedures

• Subcutaneous abdominal artificial tear pump-reservoir - treatment of severe dry eye.

• Understanding of the pathogenesis and specific cellular responses involved in different forms of DE could result in the development of other treatment strategies for a better management and long lasting results.

• Development of additional treatment options in the form of compounds targeting specific components would provide hope for the millions of individuals who daily experience this deleterious condition.