Intro to Dry Eye Disease

3 layers of tear film

• lipid layer (meibomian glands)

• aqueous layer (lacrimal glands)

• mucous layer (conjunctival goblet cells)

lipid layer

• polar phase (binds to lipocalins w/in aqueous layer)

• non-polar phase (contain waxes, cholesterol esters, triglycerides)

• precent evaporation of aqueous layer

• maintain tear film thickness

• act as surfactant allowing spread of tear film

• deficiency results in evaporative dry eye

aqueous layer function

• provide atmospheric oxygen to corneal epithelium

• antibacterial activity

• wash away debris & noxious stimuli

• facilitate transport of leukocytes following injury

• optically enhance corneal surface by abolishing minute irregularities

mucous layer

• permit wetting

  • convert corneal epithelium from hydrophobic to hydrophilic

  • lubrication

• deficiency may be feature of both aqueous deficiency & evaporative states

androgens

primarily responsible for regulating lipid production

estrogen receptors

found in conjunctiva & lacrimal glands

progesterone receptors

found in conjunctiva & lacrimal glands

lacrimal glands

stimulate aqueous secretions

goblet cells

stimulate mucus secretion

tear film components are regulated

hormonally & neurally

3 factors required for effective resurfacing of tear film

• normal blink reflex

• contact between

  • external ocular surface

  • eyelids

• normal corneal epithelium

dry eye disease

multifactorial disease characterized by loss of homeostasis of tear film and/or ocular surface

DED multifactorial condition characterized by combination of

• tear film instability

• tear film hyperosmolarity

• ocular surface inflammatory

• ocular surface damage

• neurosensory abnormalities

TFOS DEWS 1

• initial landmark study in 2007

• standardized global definition & classification

• aqueous deficient vs evaporative

TFOS DEWS 2

• provided update in 2017

• specifically regarding diagnostic & treatment algorithms

• stepwise tx based on disease severity

TFOS DEWS 3 (contemporary paradigm)

• most recent update in 2025

• expansion & increased specificity regarding diagnostic & treatment algorithms

• loss of tear-film & ocular surface homeostasis (central concept)

• match tx to individual pathogenic driver

classic paradigm

• primarily derived from TFOS DEWS 1

• aqueous deficient dry eye

• evaporative

• update w/ TFOS DEWS 2 suggested that majority of pts have mixed dry eye (aqueous deficient & evaporative

aqueous deficient dry eye

sub-type reduction of aqueous component of tears d/t comprised lacrimal gland

evaporative

instability of tear film results in tears inappropriately evaporating from surface

aqueous deficient dry eye can be further sub-divided into

• Sjogren Syndrome

• Non-sjogren dry eye

Sjogren Syndrome dry eye

autoimmune disease characterized by lymphocytic infiltration of exocrine organs (lacrimal gland, salivary glands)

Non-Sjogren dry eye

• lacrimal deficiency

• lacrimal gland duct obstruction

• reflex block

• systemic drugs (antihistamines, anticholinergics, antidepressants/ antipsychotics, beta blockers, diuretics)

antihistamines

reduction of mucosal secretions

anticholinergics

direct inhibition of exocrine gland fluid production

antidepressants/ antipsychotics

strong anticholinergic properties

beta blockers

inhibit beta-adrenoreceptors in tear glands

diuretics

reduction of overall body fluid

lacrimal reflex arc

corneal stimulus → V1 of CN5 → superior salivatory (lacrimal) nucleus CN7 → greater petrosal nerve

evaporative dry eye can be sub-divided into

intrinsic & extrinsic evaporative dry eye

intrinsic evaporative dry eye

internal abnormality which decreases tear evaporation and/or reduces tear film stability

meibomian gland dysfunction

• most common

• categorized by deficient lipid layer

• intrinsic evaporative dry eye

disorders of lid aperatur

• specifically, those which result in excessive exposure of ocular surface & incomplete blinking

• lagopthalmos, eyelid retraction, ectropion, CN7 palsy, proptosis

• intrinsic evaporative dry eye

reduced blink rate

• intrinsic evaporative dry eye

• Parkinson’s disease, sustained concentration, Botox

extrinsic evaporative dry eye

external factor which increases tear evaporation and/or reduces tear film stability (vitamin A deficiency, contact lens wear, ocular surface disease, environmental exposures)

contemporary paradigm

• based off of TFOS DEWS 3 study

• classified & identifies based on specific etiological drivers

• drivers sprit into tear film deficiencies (composition & quantity), eyelid abnormalities (negatively impacts how tear film is distributed & retained) , ocular surface abnormalities

Ocular surface disease index (OSDI)

12 question pt-reported questionnaire that covers three areas (ocular symptoms, vision related functioning, environmental triggers)

normal score for OSDI

0

severe score of OSDI

100

increased blink rate could indicate

• ocular discomfort

• compensatory mechanism to refresh tear film more frequently

• associated neurological dysfunction

decreased blink rate could indicate

• engagement of visually demanding task (most likely to increase evaporative loss)

• associated neurological dysfunction

Korb-Blackie Light Test

• aka Korb Blackie Lid-leak test

• clinical test used to evaluate the quality of the eyelid seal during eyelid closure

ocular staining

diagnostic test utilizing special dyes that highlight damaged or unhealthy areas on surface of the eye

fluorescein dye

• primarily evaluates epithelial barrier integrity (superficial cell tight junctions & glycocalyx)

• useful for identifying corneal epithelial defects, exposure-related epithelial damage, fluorescein TBUT

• considered superior for corneal assessment vs conjunctival assessment

fluorescein tear film breakup time (FTBUT)

interval between complete blink & first dry spot on the cornea after instillation of fluorescein dye

TBUT less than 10 seconds

abnormal tear film stability support diagnosis of DED

TBUT greater than 10 seconds

indicative of tear film stability

noninvasive breakup time

interval between complete blink & first dry spot on the cornea in the absence of fluorescein dye (will have shorter measurements compared to FTBUT)

lissamine green dye

primarily evaluates epithelial cell damage/devitalization irrespective of presence of mucin

lid wiper epitheliopathy

• alteration or staining of the marginal conjunctival epithelium of eyelid

• occurs secondary to increased friction while blinking between ocular surface & lid wiper

lip wiper

• small, thin strip of tissue along inner edge of eyelid

• purpose → tear film distribution, protective barrier that reduces friction

rose bengal dye

• primarily evaluates mucin/ocular surface protective layer

• specifically, stains epithelial cells that are not adequately protected by mucin-rich glycocalyx

tear meniscus height (tear prism height)

measurement of aqueous tear fluid located principally along upper & lower lid margins (indirect measure of tear volume)

Schirmer Test

diagnostic test that measures that quantity of aqueous tears produced by the lacrimal gland during extended period of time

phenol red thread test

minimally invasive diagnostic test that measures the quantity of aqueous tears produced by the lacrimal gland during period of 15 seconds (estimate of tear production)

tear film osmolarity testing

non-invasive objective diagnostic toll used to measure salt concentration of tears

normal tear film osmolarity testing

<308 mOsm/L

abnormal/suggestive of DED of tear film osmolarity testing

>316 mOsm/L

inflammadry

diagnostic testing that aids in identifying ocular surface inflammation

matrix metalloproteinase-9 (MMP-9)

enzyme produced by cells on ocular surface which breaks down components of ECM (also involved in inflammation & tissue remodeling)

meibomian gland expressability

clinical measure of how readily meibum can be expressed from meibomian glands when pressure is applied to the eyelid

Shimazaki expressability score

lower the grade the easier it is expressed and clearer

meibomography

noninvasive imaging technique used to visualize & evaluate structure of meibomian glands in upper & lower eyelids

epithelial thickness map

imaging maps that show thickness & spatial distribution of corneal epithelium across corneal surface

artificial tears

topical ocular lubricants used to supplement or replace natural tear film

low viscosity drops

• rapid comfortable lubrication

• shorter residence time

• useful for mild/intermittent symptoms

higher viscosity drops or gels

• longer residence time

• provide greater symptomatic relief for moderate to severe dry eye

• possibility of transient blurred vision

ointments

• provide prolonged lubrication

• results in significant blurred vision

lipid containing formulations

• help supplement tear-film lipid layer

• useful in cases of concomitant meibomian gland dysfunction

preserved artificial tear

• advantages: convenient, low risk of microbial contamination after bottle is open

• disadvantages: frequent instillation

PFATs

• advantages: ideal option for pts w/ significant ocular surface disease & concerns for preservatives sensitivity/toxicity

• disadvantages: cost d/t common package (single use vials)

topical corticosteroids mechanism of action

primarily bind to intracellular glucocorticoid receptors thereby altering gene transcription & decreasing inflammatory mediators & immune rxns

potent topical steroids

• deep ocular penetration

• strong anti-inflammatory effect

• higher likelihood for associated risks

soft topical steroids

• superficial ocular penetration

• weaker anti-inflammatory effect

• low likelihood for associated risks

topical immunomodulators: cyclosporine (Restasis, Cequa, VEVYE)

• MOA: calcineurin inhibitor that suppress T-cell activation through reduction of IL-2 transcription

• targets inflammatory component of dry eye disease

topical pharmaceuticals: liftegrast (Xiidra)

• MOA: LFA-1 antagonist inhibitor which prevents immune cells from binding to inflamed ocular surface cells

• targets inflammatory component of dry eye disease

ophthalmic semifluorinated alkane class: perfluorohexyloctane ophthalmic solution (MIEBO)

• has ability of forming monolayer at air-liquid interface of tear film

• only FDA drop approved for evaporative dry eye

lid scrubs

eyelid hygiene that utilizes topical cleansing interventions in hopes of mechanically removing debris and reducing microbial & inflammatory load

mechanical lid exfoliation

• aka microblepharoexfoliation, blepharoexfoliation

• in-office eyelid hygiene procedure in which controlled mechanical debridement is utilized to clean eyelashes & eyelid margins

• used to remove accumulation of epithelial debris, biofilm, collarettes

biofilm

thin, sticky layer of bacteria, oils, & dead skin cells

collarettes

waxy, cylindrical ring of debris that build up at base of eyelashes

warm compresses

external eyelid-heating therapy in which sustained warmth is applied to closed eyelids

intense pulse light (IPL)

controlled light based therapy used to reduced periocular inflammation & improve meibomian gland function

eyelid margin telangiectasia

abnormal, tiny, dilated blood vessels along edge of eyelid (representative of chronic eyelid inflammation)

MiBo ThermoFlo

thermoelectric eyelid-heating & massage system designed to liquefy thickened meibomian gland secretions & facilitate their expression

manual gland expression

procedure used to physically squeeze the meibomian glands to release thickened or blocked meibum

punctal occlusion

intentional obstruction of one or more lacrimal puncta to reduce drainage of tears through nasolacrimal system

punctal occlusion is primarily considered in pts who present w/

• reduced tear production

• persistent ocular surface dryness

• inadequate response to AT

• need to increase duration of topical medication on ocular surface

temporary punctal occlusion

often used as a trial before permanent occlusion (absorbable collagen)

semi-permanent/reversible

can be usually be removed if necessary (silicone punctal plugs)

permanent

considered when plugs repeatedly fall out or longer-term occlusion is desired (thermal/cautery punctal occlusion)

scleral lenses

larger diameter, rigid gas permeable contact lens that sits on scleral conjunctiva thereby vaulting over cornea & limbus

PROSE lenses

prosthetic replacement of ocular surface disease

Amniotic Membranes

biologic tissue derived from innermost layer of human placenta used as graft or protective “bandage” thereby facilitating corneal and/or conjunctival healing

five layers of amniotic membranes

• amniotic epithelium

• basement membrane (similar to BM of cornea & conjunctiva)

• compact layer

• fibroblast layer

• spongy layer