C L I N I C A L A N D E X P E R I M E N T A L
`
`OPTOMETRY
`
`REVIEW
`Dry eye: an update on clinical diagnosis,
`management and promising new treatments
`
`Julie M Albietz BAppSc(0ptom) (Hons)
`PhD
`School of Optometry, Queensland
`University of Technology
`
`Accepted for publication: 20 December
`2000
`
`Dry eye conditions are prevalent with one in four to five patients presenting to eye care
`practitioners having dry eye signs and/or symptoms. An intimate relationship exists
`between the ocular surface and the tear film. The cycle of tear film instability and
`ocular surface damage characteristic of dry eye conditions suggests that dry eye repre-
`sents a dysfunction of an integrated ocular surface-lacrimal gland unit. Therefore, dry
`eye is a multifactorial condition and ari approach based on clinical subtypes is required
`for diagnosis and management. There is increasing evidence that inflammation is a
`contributing and exacerbating factor in dry eye conditions and anti-inflammatory or
`immunomodulatory therapy for chronic dry eye conditions may facilitate ocular surface
`healing. Other promising new treatments for dry eye include new generation artificial
`tear polymers and preservative systems, secretagogues, topical androgen supplements
`and surgical techniques for ocular surface reconstruction.
`(Clin Exp Optom 2001; 84: 1: 4-18)
`
`Key words: artificial tear supplements, dry eye, dry eye treatments, evaporative dry eye, ocular surface disorders, tear deficient dry
`eye, tear film
`
`The concept of the 'dry eye' was initially
`used to describe symptoms of ocular irri-
`tation due to insufficiency in lacrimal
`gland aqueous tear secretion and lead-
`ing to ocular surface damage. Keratocon-
`junctivitis sicca was the term given to the
`ocular surface disease that develops in
`patients with aqueous tear deficiency.
`Over the past 30 years, knowledge of the
`pathogenic factors involved in dry eye
`states has grown significantly. Many pa-
`tients with dry eye symptoms produce a
`normal quantity of aqueous tears hut
`have other tear film and/or ocular sur-
`face disorders.'.' The definition of dry eye
`has been e x p a n d e d to include any
`anomaly in a gland associated with tear
`production or an anomaly in lid and/or
`
`blinking function in which the quality
`and/or quantity of the tear film is ad-
`versely affected and there is an inability
`to maintain a healthy ocular surface.2s
`The multifactorial nature of dry eye con-
`ditions has produced the term 'tear film
`and ocular surface disorders" as an alter-
`native to the term dry eye. This recognises
`the intimate relationship between the om-
`lar surface and the tear film and the cycle
`of tear film instability and ocular surface
`damage characteristic of dry eye. It also
`acknowledges recent suggestions that dry
`eye represents a dysfunction of an inte-
`grated ocular surface-lacrimal gland unit.","
`The ocular surfxe (conjunctiva, cornea,
`accessory lacrimal glands and meibomian
`glands), the lacrimal gland and the inter-
`
`connecting neural reflex loops appear to
`comprise a tightly integrated functional
`unit, the parts of which ac.t together and
`not in isolation.' Decreased lacrimal gland
`secretion damages the ocular surhce,
`which creates a negative feedback loop re-
`sulting in damage to the lacrimal gland.
`There are probably several mechanisms by
`which this feedback occurs:
`1. interruption or damage to the sensory
`corneal nerves
`2. damage to the lacrimal gland
`3. alteration of growth factor levels in the
`lacrimal gland following corneal dam-
`age.
`Contact lenses and corneal refractive sur-
`gery are additional factors that may create
`negative 'feedback to the lacrimal gland.'
`
`Clinical arid Expcrimental Opromrtry 84.1 January-Febi-uary 2001
`4
`
`APOTEX 1029, pg. 1
`
`

`

`Dry eye type
`
`Main Causes
`
`Tear deficient dry eye
`
`Evaporative dry eye
`
`1. Sjbgren's syndrome
`2. Non-Sjbgren's lacrimal disease
`Ageing
`Menopause
`Medicamentosa
`Cicatricial disease
`Neurotrophic keratitis
`
`Meibomian gland disease
`Lid surfacing/blinking anomalies
`Contact lens related
`Chronic allergyhoxicity
`Cicatricial ocular surface disease
`
`Table 1. Classification of dry eye: main subtypes and main causes
`(adapted from 3,
`
`The National Eye Institute/Industry
`Workshop on Clinical Trials of Dry Eye3
`has recommended a revision of the classi-
`fication of dry eye, given its multifxtorial
`nature. The major dry eye categories pro-
`posed were tear deficient dry eye and
`evaporative dry eye. In the tear deficient
`category were Sjogren's syndrome and
`non-Sjogren's syndrome forms of aqueous
`tear deficiency. Evaporative forms of dry
`eye were oil deficient (meibomian gland
`anomalies), lid surfacing and blinking
`anomalies, chronic allergy/toxicity, con-
`tact lens-related anomalies and cicatricial
`ocular surface disease (Table 1).
`Dry eye is a prevalent condition with
`one in four patients presenting for eye
`examination manifesting dry eye symp-
`toms7 and 10 to 18 per cent being diag-
`nosed with dry eye depending on the
`diagnostic criteria
`The prevalence
`of dry eye has increased in recent years
`due to the general ageing of the popula-
`tion,'O increased medication use '('and in-
`crease in environmental allergens and
`irritants.".I2 It was estimated that there
`were 30 million dry eye sufferers in the
`United States of America in 1990 and the
`incidence of dry eye increased to 59 mil-
`lion in 1997." In addition to symptoms
`of chronic ocular surface irritation, dry
`eye is characterised by blurred vision,
`
`increased risk of infecti~n,'~.'' medication
`contact lens intoleranceI6 and
`progressive ocular surface disease, scar-
`ring and corneal morbidity.'"-"' Hence
`correct diagnosis and appropriate man-
`agement of dry eye is essential.
`
`THE TEAR FILM AND OCULAR
`SURFACE
`
`The tear film is composed of an external
`lipid layer, an aqueous layer, a semi-solid
`conjunctival goblet cell mucous layer and
`the non-goblet epithelial mucin layer (the
`glycocalyx). The lipid layer is produced
`by the meibomian glands and its princi-
`pal role is to reduce tear film evapora-
`tion.2' The aqueous layer contains electro-
`lytes, glucose, antibacterial proteins,
`antibodies a n d glycoproteins a n d is
`secreted primarily by the lacrimal gland.22
`The inner layer of the tear film is com-
`posed of mucin secreted by the goblet
`cells of the c~njunctiva"~'~ and the non-
`goblet epithelial cells of the cornea" and
`
`c o n j ~ n c t i v a . ~ ~ ~ * ~ The superficial epithelial
`cells have microvilli and microplicae that
`are covered by the glycocalyx, a non-goblet
`cell mucin, which appears to anchor the
`goblet cell m u c h to the underlying sur-
`face epithelium and may facilitate tear
`film spread and stabilisation.25 The thick-
`
`Dry eye Albietz
`
`ness of the tear film remains controver-
`sial. Interferometric estimates of 40
`microns" (with the bulk of the tear film
`being mucin and the tear film thought
`to be a hydrated mucin gel) and more
`recently three microns" have been re-
`ported.
`The ocular surface epithelium is non-
`keratinised and multi-layered with mor-
`phological variations in the corneal,
`limbal and conjunctival epithelia."","' The
`corneal and conjunctival epithelial barrier
`functions are formed and maintained by
`tight, intercellular desmosomes between
`the adjacent superficial cells.92,"" The
`limbal epithelium is thought to contain
`the stem cells of the corneal epithelium
`and serves as the junctional epithelium to
`prevent conjunctival epithelial ingrowth
`onto the corneal surface during the heal-
`ing of a large corneal epithelial defe~t.:'~.''~
`The limbal epithelium represents the true
`germinative zone for corneal epithelium.
`In normal conditions, the epithelial cells
`continuously migrate from the limbus
`toward the corneal centre. This process is
`accelerated in epithelial wound healing.'iti
`As the limbal epithelial stem cells have
`very slow cycling time, loss or damage to
`the limbal area from chemical or surgical
`trauma, chronic inflammation or contact
`lens-related pathology can result in limbal
`stem cell d.eficiency a n d a gradual
`conjunctivalisation of the ~ornea.'~'
`Numerous hormones, growth factors,
`retinoids, cytokines a n d reciprocal
`receptors for these factors have been iden-
`tified in the lacrimal glands and on the
`ocular surface."-'2 The meibomian glands
`and lacrimal glands appear to require
`androgens to support their normal func-
`tion.4'-"" Androgen loss may play a critical
`role in the initiation of meibomian gland
`dysfunction, and decreases in androgen,
`particularly evident in Sjogren's syn-
`drome, may serve to lessen tissue function
`as well as to promote (but not cause) the
`autoimmune process in the lacrimal
`gland, 49.45 Programmed cell death (or
`apoptosis) of lacrimal gland acinar cells
`may be the primary event proceeding the
`damage to the lacrimal gland in tear defi-
`cient dry eye, even in the absence of
`autoimmune disease.'"
`
`Clinical and Experimental Optometry 84.1 January-February 2001
`5
`
`APOTEX 1029, pg. 2
`
`

`

`Dry eye Alhietz
`
`DRY EYE SUBTYPES: CAUSES AND
`PREVALENCE
`
`Tear deficient dry eye
`Aqueous tear deficient dry eye affects up
`to three per cent of the population and is
`more prevalent in females and the eld-
`erly."~''-"' The lacrimal gland abnormalities
`include lack of stimulation of tear secre-
`tion, inflammation and destruction of the
`lacrimal gland and accessory lacrimal
`glands and scarring or occlusion of the
`lacrimal gland secretory ducts."" The most
`severe forms of aqueous tear deficiency
`are due to destruction or absence of the
`lacrimal gland and include Sjogren's syn-
`drome," human immunodeficiency syn-
`drome," graft versus host disease"3 and
`congenital or surgical removal of the lac-
`rimal gland.' Cicatricial diseases such as
`trachoma, chemical burns, Stevens-
`Johnson syndrome and ocular cicatricial
`pemphigoid can also cause a severe sec-
`ondary aqueous tear deficiency through
`the scarring, narrowing and obliteration
`of the lacrimal gland and accessory
`lacrimal gland secretory ducts.'
`
`AUTOIMMUNE AQUEOUS TEAR
`DEFICIENCY
`Sjogren's syndrome is the main cause of
`severe aqueous tear deficiency and has a
`prevalence of approximately one per cent,
`with the majority of sufferers being
`female." '' The condition is a slowly-
`progressing, chronic multi-system condi-
`tion affecting excretory glands in all pa-
`tients and extra-glandular organs in some
`patients with the major features being
`aqueous tear deficiency and xerostomia
`(dry mouth) .i4 Approximately half of the
`cases are associated with other connective
`tissue disorders, the most common being
`rheumatoid arthritis and others include
`systemic lupus erythematosis, scleroderma
`and polymyosis.55 The disease process is
`extremely complex and the ocular com-
`ponent is characterised by lacrimal gland
`inflammation, conjunctival inflammation
`and severe ocular surface desiccation, in-
`cluding punctate keratitis, mucous fila-
`ments, corneal ulceration and scleritis'h ''
`(Figure 1 ) . Although the exact mecha-
`
`nism that triggers Sjogren's syndrome is
`unknown, it seems that some events cause
`changes in the cell membranes of the lac-
`rimal and salivary glands and the immune
`system then attacks these glands as if they
`were f ~ r e i g n . ' ~ The infiltrative cells seen
`in lacrimal gland biopsy are specific to
`Sjogren's syndrome and they differ in type
`and number from the infiltration that
`occurs as a function of ageing.'" Recent
`research indicates that androgen defi-
`ciency may promote the progression of
`Sjogren's syndrome and associated lac-
`rimal gland inflammation but does not
`cause Sjogren's syndrome or aqueous tear
`deficiency in human and animal model^.^'
`The relative roles of viral infections such
`as Epstein-Barr virus, cytornegalovirus and
`herpes virus-6 in the pathogenesis of
`Sjogren's syndrome have been suggested
`and there is evidence that these viruses
`activate or precipitate immune responses
`in the lacrimal glands, leading to
`increased inflammation."'-h'
`
`NON-AUTOIMMUNE AQUEOUS TEAR
`DEFICIENCY
`Less severe forms of aqueous tear defi-
`ciency occur due to abnormalities of the
`regulation of tear secretion. These may be
`precipitated by ageing and age-related
`alterations in hormone level^."^"^ Diffuse
`fibrosis, diffuse atrophy and periductdl
`fibrosis predominantly found in elderly
`women suggest a relationship with aqiie-
`ous tear deficiency in post-menopausal
`women.' Many commonly-prescribed oral
`and topical medications may reduce aqire-
`ous tear production including topical and
`systemic anti-histamines, tricyclic anti-
`depressants, topical and systemic beta-
`blockers, the oral contraceptive pill and
`systemic and topical non-steroidal anti-
`inflammatory agents.'''
`Loss of corneal sensitivity as is observed
`in diabetes,65 excimer laser photorefractive
`keratectomy and L.ASIK66 and contact lens
`wear,67 has been implicated in causing dry
`eye conditions through reduced reflex
`tearing'" and reduced blink rate.'' Re-
`duced tear secretion may actually lead to
`reduction in corneal sensitivity,6y thereby
`creating a cycle of declining sensitivity and
`declining tear production.
`
`Evaporative dry eye
`
`MEIBOMIAN GLAND ANOMALIES
`Meibomian gland anomalies cause the
`most prevalent form of evaporative dry eye
`with a prevalence of four per cent for lipid
`anomaly dry eye.* Approximately 40 per
`cent of the general population has signs
`of meibomian gland dysfunction'" and a
`100 per cent incidence of poor tear film
`stability and ocular surface staining has
`been reported in subjects with chronic
`meib~mianitis.~' An increased prevalence
`of meibomian gland dysfunction occurs
`with age7" due to normal ageing changes
`in the lids and meibomian glands." The
`most common causes of meibomian gland
`dysfunction are damage or destruction of
`meibomian glands due to meibomian
`seborrhoea," meibomianitis" and senile
`or cicatricial meibomian gland changes.''
`Less common causes of meibomian gland
`disease include congenital absence of
`meibomian glands,' replacement of
`meibomian glands due to congenital or
`acquired distichiasis" and meibomian
`n e ~ p l a s i a . ' ~ The dermatological condi-
`tions, acne rosacea and seborrhoeic der-
`matitis, have a 51 per cent and 74 per cent
`incidence of meibomianitis, respectively."
`Stagnation of the meibomidn gland lipids
`in meibomian gland dysfunction gives bac-
`terial lipase an opportunity to break down
`the meibomian lipid into free fatty acids
`which cause increased tear film evapora-
`tion, an unstable tear film,'> marginal
`keratitis a n d a superficial punctate
`keratopathy7' (Figures 2, 3 arid 4).
`
`CHRONIC ALLERGY
`Chronic allergy destabilises the tear film
`and can induce ocular surface di~ease.""~
`An allergic history has been reported by
`36 per cent of dry eye subject^.^ The aller-
`gic inflammatory mechanism in giant cell
`papillary conjunctivitis (GPC) causes ex-
`cessive mucin production through hyper-
`plasia of goblet cells and hypermitosis of
`non-goblet epithelial cells.7h 77 In addition,
`decrease in tear production has been re-
`ported in subjects who have nasal mucosal
`pathology following chemical destruction
`or chronic allergy resulting in reduction
`or loss of the nasolacrimal reflex." Vernal
`
`Clinical and Experimental Optometry 84.1 January-FehrudI-y 2001
`6
`
`APOTEX 1029, pg. 3
`
`

`

`Dry eye Albz
`
`Figure 1. Chronic aqueous tear deficiency in Sjogren’s syndrome.
`Corneal filaments and widespread staining are characteristic features.
`Inferior neovascular changes are secondary to aqueous tear deficiency
`and are due to chronic inflammation of the meibomian glands.
`
`Figure 2. Marginal infiltrative keratitis associated with meibomii
`seborrhoea
`
`Figure 3. Particulate meibomian gland debris in the tear film. The
`significant nasal pterygium will exacerbate the evaporative dry eye
`condition caused by the meibomian gland dysfunction.
`
`Figure 4. Trichiasis, madarosis, lid thickening and telangectas
`associated with chronic meibomian gland dysfunction. Staphylococ
`blepharitis is also present.
`
`Figure 5. Micro- and macropapillae in vernal kerato-conjunctivitis. The
`larger papillae can act as a foreign body, further disrupting the ocular
`surface.
`
`Figure 6. Lid surfacing anomalies causing increased tear evaporatiot
`large fleshy pterygium and senile ectropion
`
`Clinical and Experimental Optometry 84.1 January-Fchrudry 200 I
`7
`
`APOTEX 1029, pg. 4
`
`

`

`Dry eye Albietz
`
`keratoconjunctivitis is associated with a 38
`per cent incidence of dry eye7' (Figure 5).
`
`OCULAR SURFACE TOXICITY
`Toxic effects of topical therapeutic agents
`can result in ocular surface damage, in-
`flammation and tear film disruption.H"
`Preservatives such as benzalkonium chlo-
`rideX'.Hi . and cetrimideH4 are known to be
`toxic to the epithelium. Intrinsic toxicity
`ran also result from the active ingredient
`in the medication itself. For example,
`long-term use of topical anti-glaucoma
`medications can induce and/or exacer-
`bate dry eye conditions through squamous
`metaplasia, loss of goblet cells and ocular
`surface inflanimation.K'X'
`
`CONTACT LENS WEAR
`Dry eye is prevalent in contact lens weaF ''
`with 20 to 30 per cent of contact lens wear-
`ers having dry eye symptoms.q" Contact
`lens wear is associated with increased
`mucous production,' reduced blink fre-
`quency,'" blink inefficiency," 3 and 9
`o'clock staining,'" reduced tear break-up
`time," increased tear evaporation" and
`increased tear osmolarity," all of which
`can produce and/or exacerbate dry eye
`signs and symptoms.
`
`CICATRICIAL OCULAR SURFACE DISEASE
`Cicatricial ocular surface diseases, al-
`though rare, can result in gross tear film
`instability through destruction of ocular
`surface epithelia, loss of goblet cells and
`cicatricial changes such as symblepharon
`and scarring of lacrimal gland ductiiles.lq
`These conditions are potentially the most
`vision-threatening of all dry eye types with
`limbal stem cell loss and conjunctival-
`isation of the cornea being potential con-
`sequences of cicatricial disease.
`
`LID SURFACING ANOMALIES
`Dry eye due to lid surfacing anomalies
`affects approximately two per cent of the
`population. Any anomaly preventing or
`restricting complete lid closure and nor-
`mal blinking patterns can disrupt tear film
`stability, increase tear evaporation and in-
`iuce ocular surface staining."' Potential
`Iauses are ectropion, entropion, large
`>terygia,"+ facial palsies, symblepharon,'
`
`nocturnal
`blinking,
`incomplete
`lagophthalmos,g6 lid retraction and prop-
`
`tosis in thyroid d i ~ e a s e , ~ ' involuniary
`blepharospasm,gH dermatochalasis,gq
`conjunctivochalasis,'"" lower lid laxity'"'
`
`and contact lens wear.L6~q1~10L? Extensions of
`the interblink period due to intense ion-
`centration during close work and compu-
`
`ter work con~entration"'","'~ and in Parkin-
`son's disease may lead to dessication of
`the ocular surface." Reduction in lid ri-
`gidity and tonus occurs with age.lo5 Dellen
`occur in lid surfacing anomalies in asso-
`ciation with pterygia, pingueculae and
`contact lens wear I H (Figure 6).
`
`ENVIRONMENTAL INFLUENCES
`
`Environmental factors such as dehydrat-
`ing temperature-controlled environ-
`ments"' can cause or contribute to
`evaporative dry eye conditions. Several
`terms have been used to describe the ocu-
`lar irritation, poor tear film stability and
`ocular surface desiccation associated with
`the poor indoor air-quality in tempcra-
`ture-controlled office environments.
`These include 'pollution keratoconjunc-
`tivitis',lL 'office dry eye syndrome' and
`'sick building syndrome'."'" Studies irtdi-
`cate that 35 per cent to 48 per cent of in-
`dividuals working in such environments
`are afflicted by the ocular signs and/or
`symptoms. lo'' ""
`
`The multifactorial nature of
`dry eye
`A dry eye condition can have multiple
`causative mechanisms."'" A common ex-
`ample is the elderly, post-menopausal,
`te ar-d e fi c i en t pa tie n t taking systemic
`medications that further reduce tear pro-
`duction.l"q~"" In chronic forms of dry eye,
`the complications from the primary con-
`dition can cause a secondary source of tear
`film instability and a further exacerbation
`of the ocular surface disease. An associa-
`tion between tear deficient dry eye and
`evaporative dry eye has been reported by
`several authors. McCulley and coworkers"
`reported a 25 per cent to 40 per cent inci-
`dence of aqueous tear deficiency in sub-
`jects with conditions of meibomian gland
`dysfunction. Chronic lid inflammation
`
`from meibomian gland dysfunction may
`cause scarring of lacrimal and accessory
`lacrimal gland ductules, subsequently re-
`sulting in deficiency in aqueous tear pro-
`duction14 (Figure 4). Alternatively, con-
`centration of tear proteins at the inferior
`lid margin resulting from reduced aque-
`ous tear production can induce inflamma-
`tion in meibomian glands." Meibomian
`gland anomalies are commonly reported
`in Sjogren's syndrome."'.11'
`
`The tear film and ocular surface
`in dry eye
`Specific deficiencies of tear components
`have been identified in dry eye. These in-
`clude deficiencies in tear proteins (for ex-
`ample, lactoferrin, lysozyme, preal-
`bumin) 114.114 a n d growth factors (for
`example, epidermal growth factor, trans-
`forming growth factors)'I5 and increase in
`inflammatory cells."l,"h
`In all forms of dry eye, irrespective of
`the mechanism, the conjunctival ocular
`surface undergoes squamous metaplasia,
`a progressive transition to a non-secretory,
`keratinised epithelium.xi',l'7.'1X The loss of
`conjunctival goblet cells appears to he a
`very sensitive indicator of ocular surface
`disease.'""' Goblet cell loss occurs within
`weeks of the onset of dry eye
`There also appears to be an alteration to
`conjunctival mucin distribution and/or
`chemical properties in dry eye."' Inflam-
`matory mechanisms are the most likely
`cause for the loss of goblet cells in dry
`eye.l".ll9 Up regulation of immune-
`mediated markers of conjunctival ocular
`surface inflammation and infiltration of
`T-lymphocytes occur in the conjunctival
`epithelium in both Sjogren's syndrome
`and non-Sj(jgren's dry eYe,!i~,Kl.l??~121~ The in-
`flammatory mediators released as a result
`of cellular damage appear to exacerbate
`the ocular surface and lacrinial gland in-
`flammation and damage in dry eye."7~1:"'
`
`CLINICAL DRY EYE ASSESSMENT
`
`While there are many tests for dry eye,
`there remains a great disparity among the
`symptoms and signs in many dry eye pa-
`tients. Determining the cause of dry eye
`when minimal clinical signs are present
`
`Clinical and Exprririirntdl Optometry 84.1 January-February 200 I
`8
`
`APOTEX 1029, pg. 5
`
`

`

`Dry eye Albietr
`
`is difficult and the diagnosis is compli-
`cated further when there is a lack of cor-
`relation between symptoms and objective
`tests1'' In an attempt to overcome these
`problems and to standardise the diagnos-
`tic criteria for dry eye, the National Dry
`Eye Institute/Industry report has pro-
`duced the following global criteria' for
`clinical diagnosis of dry eye:
`1. a validated test of dry eye symptoms
`2. reduced tear film stability
`3. ocular surface staining
`4. tear hyperosmolarity.
`
`Symptoms
`Although dry eye is represented by vari-
`ous dysfunctional states involving the tear
`film, ocular surface, lids and blinking, dry
`eye symptoms are generally not subtype
`specific. Commonly reported dry eye
`symptoms are grittiness, foreign body sen-
`sation, burning, soreness, stinging,
`scratchiness, dryness, blurry vision, a 'film
`over the eyes', paradoxical reflex tearing
`and photophobia,lH.20.Y~.."~
`Clinical evaluation of dry eye should in-
`clude an assessment of subjective symp-
`toms and functional lifestyle, through the
`use of a well-designed and validated dry
`eye questionnaire." Until recently, the
`McMonnies Dry Eye Symptom Survey was
`the only questionnaire to meet these
`requirements and provide a formal aid to
`dry eye history-taking in clinical prac-
`
`t i ~ e . " ' . ~ ~ ~ The recently introduced Ocular
`Surface Disease Index (OSDI)IS5 is a
`12-item questionnaire designed to provide
`a rapid assessment of the symptoms of
`ocular irritation with dry eye disease and
`their impact on visual function. The
`OSDI correlates significantly with the
`McMonnies questionnaire and appears to
`be a valid and reliable method of measur-
`ing the severity of dry eye disease and pos-
`sesses the necessary psychometric proper-
`ties to be used as an end point in clinical
`trials.136 While the OSDI has not yet been
`published,
`its advantage over
`the
`McMonnies Survey is that it is not biased
`towards diagnosis of aqueous tear deficiency.
`Tear film stability
`Tear film instability is a non-specific test
`for dry eye. All tear film stability tests have
`
`poor repeatability and a mean of multi-
`ple measures is recommended."'A recent
`study indicated a significant correlation
`between ocular surface discomfort and
`tear film break-up time in dry eye sub-
`jects.'?" The most common clinical meas-
`ure of tear film stability is fluorescein
`break-up time (FBUT) which has a refer-
`ence value of less than 10 seconds for dry
`eye."' As instillation of large volumes of
`fluorescein destabilise the tear film, an
`effort should be made to control the vol-
`ume of fluorescein instilled in the eye.
`The Dry Eye Test (DETTM) is a newly-
`released thin fluorescein strip which de-
`livers only one microlitre of fluorescein
`into the eye, compared to 10 microlitres
`for a standard fluorescein strip, hence im-
`proving the accuracy and reproducibility
`of FBUT measurements."" It is not yet
`available in Australia. Non-invasive meth-
`ods of tear film instability such as the
`keratometer mires and Keeler Tearscope
`PlusTu give longer tear film stability meas-
`ures and a value less than 20 seconds war-
`rants further investigation.
`
`Ocular surface staining
`Fluorescein and rose Bengal are the two
`most widely-used ocular surface stains.
`Rose Bengal stains dead and devitalised
`cells, mucous strands and areas where the
`mucous layer of the tear film is discon-
`tinuous."" Fluorescein lacks this ability to
`be blocked by tear constituents and dif-
`fuses rapidly into the stroma where cell
`to cell junctions are disrupted."'
`Fluorescein acts as a vital stain adhering
`to devitalised cells.'"' Unlike rose Bengal,
`fluorescein does not stain mucus.
`Lissamine green B is an alternative to rose
`Bengal that is more easily t01erated.l~"
`Lissamine green B is identical to rose Ben-
`gal in its staining properties but it stains
`blue on the ocular surface and it is easier
`to distinguish against an inflamed con-
`j u n ~ t i v a . " ~ It is not yet available in Aus-
`tralia.
`Fluorescein and rose Bengal staining are
`highly sensitive for dry eye diagnosis but
`mild staining has been found in 30 per cent
`to 40 per cent of normals."' Various semi-
`quantitative fluorescein and rose Bengal
`staining schemes have been described. The
`
`most widely used staining grading schemes
`are those proposed by Lemp,3 van
`
`Bji~terveldl~~ and the Oxford scores.14h
`The location of ocular surface staining
`can be a significant indicator of the cause
`of a dry eye c ~ n d i t i o n . " ~ ~ ' ) Examples
`include:
`1. Non-autoimmune aqueous tear defi-
`ciency is characterised by inter-
`palpebral staining, whereas in autoim-
`mune aqueous tear deficiency the
`staining is more widespread and may
`be confluent'" (Figure 1 ) .
`2. Meibomian gland anomalies are gen-
`erally associated with staining along the
`inflamed lid margins and 4 and 8
`o'clock corneal staining, where the
`inflamed lid margins meet.'47
`3. Lid surfacing anomalies are associated
`with staining in the region of ocular
`surface exposure, which is generally in-
`ferior in senile and cicatricial ectro-
`pion, lower lid laxity and nocturnal
`lagophthalmos, interpalpebral in cases
`of incomplete blinking, large fleshy
`pterygia and pingueculae or wide-
`spread in thyroid eye
`4. Staining of the plica semilunaris and
`caruncle is indicative of allergic condi-
`tions, where habitual eye rubbing and
`'mucus fishing' may develop.5"
`5 . Toxic papillary reactions are character-
`ised by widespread corneal staining
`extending inferonasally to the conjunc-
`tiva in non-contact lens wearers. A simi-
`lar pattern of staining is seen in contact
`lens wearers with toxic papillary reac-
`tions. However, the staining is more in-
`tense in the superior limbal region."
`6. Contact lens associated dry eye is most
`likely to be associated with a 3 and 9
`o'clock or 4 and 8 o'clock staining in
`rigid gas permeable contact lens wear
`or inferior corneal exposure staining
`in soft contact lens wearers. Any type
`of contact lens can be associated with
`non-specific widespread staining when
`soiled lenses are worn."'
`Tear film osmolarity
`Hyperosmolarity is a contributing mecha-
`nism in ocular surface damage and inflam-
`mation associated with aqueous tear
`deficiency and meibomian gland dys-
`
`Clinical and Experimental Optometry 84.1 January-February 2001
`9
`
`APOTEX 1029, pg. 6
`
`

`

`Dry eye Albirtz
`
`function." However, in the absence of
`a simple clinical technique to measure
`tear osniolarity, this diagnostic test will
`remain a research tool for the present.' ""
`
`Global dry eye diagnostic protocol
`Golding and Brennan"" researched the
`diagnostic accuracy of 20 common clini-
`cal tests for dry eye and determined that
`a protocol comprising the symptoms, sta-
`bility arid staining tests of McMonnies dry
`eye symptom survey score equal to or
`greater than 14, rose Bengal staining score
`of one or greater and FBUT less than 10
`seconds, gave an optimal dry eye diagnos-
`tic accuracy with sensitivity of 93 per cent
`and specificity of 100 per cent. Clinical
`differential diagnosis of dry eye types can
`h e made primarily o n the basis of
`biomicroscopic signs.x 'IiH
`
`CLINICAL DIAGNOSIS OF TEAR
`DEFICIENT DRY EYE
`
`Diagnostic work-up for tear deficiency
`should incorporate a detailed medication
`history (to identify medications inhibiting
`aqueous tear production), general health
`history (to identify related systemic con-
`ditions) and at least one test of tear secre-
`tion."' Tear secretion tests include the
`Schirmer and Jones tests, phenol red
`thread tear test (PRT) and fluoro-
`photometry. These tests have only fair
`reproducability.'"'~''' Hence, tear defi-
`ciency diagnosis cannot be made on the
`basis of tear secretion alone. The Schirmer
`I test'"' and Jones testl"'measure basal and
`reflex tear secretion, respectively, and are
`the most commonly-used clinical tests.""
`The Jones test involves application of topi-
`cal anaesthetic a few minutes before in-
`stillation of the Schirmer test strip into the
`lower fornix, whereas the Schirmer I test
`involves conjunctival stimulation and the
`Schirmer I1 test involves nasal stimula-
`tion.'% Normal values with and without
`anaesthetic are more than 5 mm over five
`minutes and more than 10 mm over five
`minutes, respectively.'54 Schirmer strips
`can cause significant patient discomfort
`and ocular surface disturbance when the
`poorly wetted strip fails to soften in a dry
`eye subject. lii
`
`The PRT test has been described as a
`measure of tear volume and turnover
`rather than basal tear secretion."" PRT test
`values have not been found to correlate
`with Schirmer test values.'"; Evaluation is
`made by measuring the quantity of tears
`absorbed into a fine cotton thread placed
`A normal value
`in the inferior
`of 24 mm over 15 seconds has been re-
`corded for a Caucasian population.'"" A
`PRT test value of less than 11 mm in
`15 seconds is diagnostic of aqueous tear
`deficiency."" The PRT test can effectively
`differentiate between tear deficient and
`non-tear deficient dry eye and between
`tear deficient dry eye and non-dry eye
`subjects. "Ix
`A number of biomicroscopic signs are
`specifically associated with tear deficient
`dry eye. These include a scant inferior tear
`meniscus,"g dull pre-corneal tear film
`specular reflection,'"" lid parallel conjuiic-
`ti"al folds, ' l 7 ' , ' 6 ' particulate matter in the
`tear film,"'" tear film mucous debris and
`mucin filament^.'"^
`Using fluorophotometry, tear flow and
`tear volume can he evaluated by measur-
`ing the decay of sodium fluorescein in
`the tear film after its topical applica-
`tion."" Tear turnover rate is approni-
`mately 42 per cent lower in dry eye sub-
`jects than in normals.""' The fluorescein
`cle