Dry eye disease : A

review of diagnostic

approaches and

TreatmentsSaudi journal of ophthalmology (2014)28,173-

181

Hui Lin,MD,PhD;Samuel C.Yiu,MD,PhD

Presented By – Dr. Dildar Singh

Moderator - Dr. K.Kanthamani

“Dry eye is a multifactorial disease of the tears andocular surface that results in symptoms of discomfort,visual disturbance and tear film instability with potentialdamage to the ocular surface. It is accompanied byincreased osmolarity of the tear film and inflammation ofthe 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 ofreduced stability and increased tear film osmolarity.

- ADDE chiefly refers to a failure of lacrimal secretion andEDE is due to excessive water loss from the exposed ocularsurface in the presence of normal lacrimal secretoryfunction.

Diagnostic assessment

An ideal diagnostic method should be preferably non-invasive,objective, specific, reproducible and sustainable in terms ofcost 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 toensure consistency in recording symptomatic information.

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

Objective evaluation :

a) tear film assessmentc) the Schirmer test as the most commonly used diagnostictests 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 IIf 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'ssyndromeIf Wetting increases by 1mm Non-Sjogren'ssyndromeSCHIRMER'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 byevaporation.

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

a) tear hyperosmolarityb) tear film instabilityc) 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 , remainsthe most frequently used diagnostic test to determine tearfilm instability.

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

NIBUT can be measured by:

a) corneal topographyb) interferometry c) aberrometryd) functional visual acuity assessmente) 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 betweenlight reflected from the surface of the lipid layer andfrom the interface between the lipid layer and theaqueous layer of the tear film.

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

C) Aberrometry

WAVEFRONT ABERROMETER

• non-invasive assessment of the visual disturbancescaused by higher order aberrations arising from tearfilm instability and break-up.

• Aberrometry could be utilized for not only detectingDE but also for monitoring the efficacy oftreatments.

D) Functional visual acuity

• measure of visual acuity during sustained eyeopening without blinking

• defined as the monocular recognition acuity at aspecific time point

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

Optical coherence tomography

• Anterior segment OCT can measure the tear filmthickness and tear meniscus parameters which indicatetotal tear volume.

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

E) Non Contact Confocal Microscopy

• non-contact, tandem-scanning confocal microscopedemonstrating real-time images to observe the tearfilm.

Evaluation of ocular surface and inflammation

Confocal microscopy

Meibomian gland evaluation

Corneal and conjunctivalstaining

Conjunctival impression cytology or brush cytology

Other tests

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

1) Confocal Microscopy

• IVCM enables the study of:-a) corneal epitheliumb) corneal stroma and keratocytesc) endothelial cells,d) corneal nervese) corneal immune and

inflammatory cellsf) conjunctivag) 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 lampb) Meiboscopyc) Meibographyd) Meibometry

2) Meibomian gland evaluation

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

a) sodium fluoresceinb) rose bengalc) 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 devitalisedepithelial 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 - absentScore 1-just presentScore 2-moderate stainingScore 3-gross staining

• Dark green, water soluble

• Degenerated cells, mucus, dead cells

• Less irritating

Lissamine green

• harvesting conjunctival epithelial,Goblet, and inflammatorycells from the bulbar mucosa

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

• dry eye group was found to have a significant difference in theCD4/CD8 ratio

• Elevated matrix metalloproteinases levels in DE

4) Conjunctival impression cytology or brush cytology

Treatment

• Artificial tears provide palliative relief to eye irritation inpatients with aqueous tear deficiency, but do notprevent the underlying inflammation

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

Severe- autologous serum, oral tetracyclines, prostheticlens, and systemic immunesuppressants

Severe forms associated with systemic diseases- surgicalintervention, including tarsorrhaphy and amnioticmembrane transplant.

Additionally, a stepwise guide to approach thebest combination of medications to avoidsymptoms of DE was also recommended

Anti-inflammatory treatments

Supplementary treatments

Surgical treatment

Anti-inflammatory treatments :

• Cyclosporine A Controls inflammationIncreasing tear secretion Tear film stabilityRestoring epithelial damageReducing 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-inflammatoryOmega-6 FAs Proinflammatory.

Topical administration of resolvin E1, an omega-3 FAderivative increased tear production, helped maintain ocularsurface integrity, decreased cyclooxygenase 2 expressionand decreased immune cell infiltration in experimental dryeye.

• Nerve growth factor (NGF) Increase ocular surface sensitivity,

Inhibit inflammatory reactions, Regulate tear film production,Reducing the apoptosisof corneal epithelial cells triggered by hyperosmolarity .

• Autologous serum Autologous and umbilical cord serum contains substancesthat support the proliferation, differentiation, and maturationof the normal ocular surface epithelium and therefore, findsapplication in the treatment of severe DE.

• Acupuncture

Surgical treatment

• Punctal occlusion Reduces drainage, preserves naturaltears 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.