Dry eye disease (DED) is a complex, multifactorial diseased instigated by inadequate tear production and/or rapid tear film evaporation as a result of a multitude of risk factors including ageing, reduced androgen levels, exogenous oestrogen use, dietary imbalance, inflammatory disease, environmental factors and gender (females at higher risk).1-2
DED causes ocular discomfort, fatigue and visual disturbance which, in turn, interfere with the daily activities of individuals and thus negatively impact on their physical and mental functions.3-4 Subsequently DED symptoms have been shown to adversely impact on quality of life.5 Health utility indexing reports moderate-to-severe dry eyes at a similar level to moderate-to-severe angina.6 According to the World Health Organisation the prevalence of depression, already the fourth largest contributor to global disease burden7 is expected to increase.8 Depressive mood and depressive mood disorder have been associated with various systemic diseases such as cardiovascular diseases,9 metabolic disorders10 and obesity11 and more recently population-based studies have also indicated a statistically significant association between DED and depression and anxiety.11-17 The effect of DED is often underestimated by practitioners despite this.
Epidemiology
DED is among the most common conditions treated by ophthalmology, indicated by the fact that its global prevalence is estimated to range from 11% to 52% in the general population.18-21 The numbers of dry eye patients attending community optometric practices has increased thanks to a demographic shift towards a more elderly population, the ocular rigours of the modern workplace and the proliferation of digital devices22, and an apparent increase in referrals from general practitioners/pharmacists to optometry. Added to that the positive change in public perception towards seeing optometrists as the first port-of-call for ocular issues, and all of this has had an accumulative impact. This increase coincides with an escalation in optometrist upskilling (particularly via Additional Supply and Independent Prescribing qualifications) and provides an excellent and exciting opportunity for practitioners to start a dedicated dry eye service within their practice. Dry eye assessment could be viewed as a natural extension of the contact lens examination as it requires a similar skill set to that already well-established within the profession.
Definition and classification
Dry eye can be classified into two main categories aqueous deficiency dry eye (ADDE) and evaporative dry eye (EDE), each with numerous branches and further sub-divisions as outlined by the 2007 Report of the International Dry Eye WorkShop (DEWS) (see figure 1).
Figure 1: Dry eye’s two main categories
Aqueous Deficiency Dry Eye (ADDE)
In ADDE, a failure in the lacrimal tear secretion leads to tear hyperosmolarity. This in turn induces hyperosmolarity of the ocular surface epithelial cells and stimulates a cascade of inflammatory events.23-26 ADDE can be sub-divided into Sjögren’s syndrome dry eye (SSDE) and non-Sjögren’s dry eye (NSDE). Sjögren’s syndrome (SS) is an exocrinopathy in which the lacrimal and salivary glands are targeted by an autoimmune process.27-30 SS can be sub-divided into primary SS which describes the occurrence of ADDE combined with symptoms of dry mouth and the presence of autoantibodies and secondary SS which consists of the features of primary SS in conjunction with an associated autoimmune disease such as rheumatoid arthritis, systemic lupus erythematosus, Wegener’s granulomatosis, etc.31-34
NSDE is a form of ADDE where the underlying systemic autoimmune features indicative of SSDE have been ruled out in the presence of lacrimal dysfunction. NSDE has many potential forms and occur either as a result of some form of lacrimal gland deficiency,35-40 obstruction of the lacrimal gland ducts41-46 or reflex hyposecretion as a result of reflex sensory block47-55 (change in trigeminal sensory input from nasolacrimal passage and eye) or reflex motor block56-57 (damage to VII cranial nerve).
Evaporative Dry Eye (EDE)
Evaporative dry eye is described as an excessive water loss from the exposed ocular surface in the presence of normal secretory function.58 This can be due to intrinsic disease affecting lid structures or dynamics as seen in meibomian gland dysfunction,59-62 disorders of the lid aperture and lid/globe congruity (craniostenosis, endocrine exophthalmos, high myopia)63-66 and low blink rate.67-68 Or as a result of extrinsic causes such as ocular surface disorders (caused by vitamin A deficiency,69-70 chronically applied topical anaesthetics71-72 and preservatives such as benzalkonium chloride),73 contact lens wear74-78 and chronic ocular surface disease such as allergic conjunctivitis.79-80
Establishing a dry eye clinic protocol
The aim of a dry clinic should be to evaluate and examine the potential causative mechanisms of dry eye and understand the basis for the patient symptoms. The modern practitioner has a plethora of diagnostic tools at his/her disposal. Such tools can aid in proper diagnosis of the sub-type of dry eye and help in establishing a successful treatment regime. The overview below is by no means exhaustive.
Clinical history and qualitative symptom assessment
Research has shown that clinicians make a diagnosis from the patient’s history in 70% to 90% of cases.81- 83 A detailed and careful history will help guide your clinical investigations. There are a number of reliable dry eye questionnaires with quality of life measures available for clinic use including the Ocular Surface Disease Index (OSDI), the Impact of Dry Eye on Everyday Life questionnaire (Ideel), Dry Eye Questionnaire (DEQ), McMonnies’ questionnaire (MQ), McCarty symptoms questionnaire, Schein questionnaire and System for Patient Evaluation of Eye Dryness (Speed). The results of questionnaires cannot be used interchangeably but can be used to quantify patient symptoms at any given point. Results can be used to gauge improvements in patient symptoms over time with treatment. The results of the Speed questionnaire correlate with parameters of evaporative dry eye and OSDI values are more correlated to parameters of aqueous tear-deficient dry eye. However, a distinction between evaporative and aqueous tear-deficient dry eye is not possible based only on the results of the questionnaires.84
Tear hyperosmolarity
Tear hyperosmolarity is regarded as a central mechanism causing ocular surface inflammation, damage, symptoms, and the initiation of compensatory events in dry eye. It is thought that tear hyperosmolarity arises as a result of water evaporation from the exposed ocular surface, in situations of a low aqueous tear flow, or as a result of excessive evaporation, or as a combination.
Hyperosmolarity stimulates a cascade of inflammatory events in the epithelial surface cells85 these inflammatory events lead to apoptotic death of surface epithelial cells, including goblet cells86 thus, goblet cell loss may be seen to be directly related to the effects of chronic inflammation.87-88 Goblet cell loss is a feature of every form of dry eye. Systems such as TearLab allow for measurement and quantification of tear osmolarity within a practice setting and could be useful in diagnosis and monitoring of DED. As an objective measure of dry eye, hyperosmolarity is attractive as a signature feature, characterizing dryness. A number of studies, including the study of goblet cells, suggest a diagnostic cut-off of = 316 mOsmol/L.
Tear film instability and tear film break-up time
In some forms of dry eye, tear film instability may be the originating event, unrelated to prior tear hyperosmolarity. The slit lamp is a key piece of instrumentation in the assessment of DED (see figure 2). High magnification and excellent optics are required to observe the structures and integrity of the tear film using specular reflection and the interference colour phenomenon. A keratometer can also be employed to assess tear stability by observing the clarity of the mires between blinks.89
Figure 2: Slit lamps are key to assessing DED
Tear film break up time (TFBUT) values of between =5 and < 10 seconds have been established as the cut-off points for dry eye diagnosis.90 Instillation of fluorescein and the use of a yellow barrier filter (eg Wratten 12) to enhance the visibility of the breakup of the fluorescent tear film is the most common technique in clinical practice, but is however a subjective and invasive technique. It is possible to assess TFBUT with non-invasive methods including tear film lipid layer interferometry91-92, the Xeroscope and the Tearscope.93-94 However, these techniques remain subjective and have been shown to suffer from poor-to-moderate repeatability.
Non-invasive tear film breakup time (NIBUT) offers a more useful insight into tear film instability. Existing equipment can be adapted and modified to help assess NIBUT such as use of a Loveridge grid and Keeler keratoscope or a Bausch and Lomb keratometer combined with a HIR-CAL grid.95-96 Newer technologies (such as the Oculus Keratograph 5) offer an automated non-invasive, objective method for qualitative and quantitative tear film assessment using a corneal topographer (see figures 3 and 4).
Figure 3: The Oculus Keratograph 5M
An index known as the Ocular Protection Index (OPI) can be used to quantify the interaction between the Inter Blink Rate (IBI) and TFBUT. The OPI is calculated by dividing TFBUT by the IBI. If the OPI score is < 1, a patient’s cornea is at risk for exposure, and if the OPI score is > 1, it is not. This approach to measuring alterations in TFBUT has proven to be useful in assessing factors that cause dry eye and evaluating therapies.97
Figure 4: Corneal topographer
Ocular surface staining and grading
Evaluation of the anterior surface of the eye via diagnostic stains such as sodium fluorescein (NaFl), lissamine green (LG) and rose Bengal (RB) plays an important step in determining the integrity of the anterior surface of the eye and aids in the diagnosis and management of DED. This is most commonly achieved using NaF which stains damaged cells and detects corneal epithelial defects. Quantifying clinical findings via the use grading scale systems such as the van Bijsterveld system,98 the Oxford system,99 the CLEK system or the Cornea and Contact Lens Research Unit (CCLRU) scale is beneficial in standardising processes and useful in serial analysis of clinical signs. Automated hyperaemia grading systems are now available (see figure 5).
Figure 5: Automated hyperaemia grading system
Lissamine green and rose Bengal have been found to produce similar staining patterns, however RB causes ocular discomfort therefore LG is preferred. LG provides a better staining agent than NaFl for the conjunctiva100; viewing can be enhanced using a ‘red coloured’ Wratten 25 filter. It is also important to allow one to four minutes to allow for adequate staining of LG and to initially use lower illumination to avoid bleaching out finer details of staining (see figure 6).
Figure 6: Ocular surface staining
Tear volume
Conventional tear volume tests (such as Schirmer I test and Phenol red thread tests) are invasive, can be influenced by reflex tearing and thus suffer from variability in test results.101-102 Advances in technology have enabled non-invasive evaluation of the tear film. The tear meniscus represents 75% to 90% of the total tear fluid volume and serves as a tear reservoir which supplies tears to the pre-corneal tear film.103-104 The tear meniscus height (TMH) is a sensitive indicator of tear volume and potentially an important marker in the diagnosis of ADDE.105-106 The TMH can be measured using a slit lamp microscope image capture system,107 reflective meniscometry,108 optical coherence tomography (OCT)109 and via Placido disc based corneal topographers such as the Oculus Keratograph 5M (see figure 3).110 A decreased TMH in dry eye has been described, with the TMH correlating with the Schirmer test score, tear film breakup time (TBUT), and dry eye severity.111
Eyelid and meibomian gland assessment
Careful and detailed examination of the eye lids (eg scarring, blepharitis), blink quality (can be affected by lagophthalmos, enophthalmos, exophthalmos, etc), bulbar conjunctiva (for signs of conjunctivochalasis also known as lid-parallel conjunctival folds, these are associated with foreign- body sensation and watering), palpebral conjunctiva (for signs of allergic eye disease; an allergic response can affect mucus production and tear lipid layer stability, reducing TFBUT) and meibomian glands (signs of meibomian dysfunction) as are important in the differential diagnosis of DED.
Meibomian gland dysfunction (MGD) is one of the most common abnormalities seen in ophthalmic practice112 causing an abnormality of the tear film lipid layer113 resulting in the evaporative dry eye.114 MGD can be diagnosed by lid morphology, MG mass, gland expressibility, lipid layer thickness and loss of MG by meibography. Meibography is a technique to visualize the morphology of the meibomian glands. Systems such as LipiView and Oculus Keratograph 5M allow in practice meibography (see figure 7).
Figure 7: In practice meibography
Case history
This series of articles aims to showcase the variety of diagnostic techniques and treatment options for the wide variety of dry eye patients that may present in primary optometric practice.
History and symptoms
A 44-year-old female attended complaining of dry, gritty eyes, photosensitivity particularly when using her computer screen at work and at times painful discomfort around her eyes. Her symptoms are cumulative throughout the day and are now adversely affecting her ability to perform work duties to such an extent she is considering quitting her job. The use of sunglasses is required to get through the afternoon when working on her VDU. Her symptoms had been building over the previous 4 years and as a result she is becoming somewhat depressed. She has previously attended the hospital eye service and numerous other eye care professional. Previous eye examinations had diagnosed ‘dry eye’ for which the patient had been advised or prescribed numerous and varying artificial tears and ocular lubricants including 0.05% cyclosporine ophthalmic emulsion (RESTASIS) but these had not proved beneficial.
Past ocular health
Myopia onset in mid-teens. Chronic ‘dry eye’ for four to five years. Lapsed contact lens wear as a result of poor comfort. No previous ocular trauma, ocular surgery or refractive surgery. No history of allergic eye condition or inflammation.
Family ocular health
Both parents myopic and with age-related cataracts.
General health
In good health. No known allergies.
Medications and supplements:
oral contraceptive, multi-vitamin supplement.
Refraction
R: -9.00 / +1.00 X 158 (6/5 N5) L: -7.50 / +0.50 X 180 (6/5 N5)
Examinations
Posterior pole normal . Posterior OCTs within normal limits for age. Pupil response normal IOPs R: 17mmHg L: 16mmHg. Threshold visual field full and normal.
SPEED Questionnaire score: 25/28 – severe symptoms
Initial differential diagnosis
Aqueous deficient dry eye
Evaporative dry eye
Neuropathic dry eye
Blepharitis
Clinical Assessment
See table 1
Initial Diagnosis
Evaporative dry eye as a result of meibomian gland dysfunction.
It is important to note that the extent of the patients symptoms and SPEED Index score vastly outweigh the visible clinical signs.
Management Plan
Due to the extent and severity of the patient’s symptoms and the failure of previous treatment interventions I felt the combined use of topical and systemic medication in conjunction with lid heating, massage and cleaning and lipid based ocular lubricants would yield the best outcome.
Topical medication
Topical corticosteroid eye drops (FML Liquifilm Ophthalmic 1 mg/ml eye drops, suspension) four times per day for one week, three times per day for one week, twice per day for one week, once per day for one week
Systemic medication
Oral antibiotics (Doxycycline 100mg) once per day for 8 weeks
Adjunctive treatment
EmustilTM eye drop emulsion (7% Soybean oil, 3% Natural Phospholipids) four times per day, HYLO-Forte eye drops (0.2% Hyaluronic Acid) as a required throughout day, if symptomatic
Lid-heating, massage, and cleaning
MGD Rx Eye Bag for 10 minutes once/twice per day. Massage upper and lower lid immediately after heat application. Clean eyelids after expression with Blephasol Duo (patient already using and enjoying this product).
Advice
Increase hydration, reduce caffeine and alcohol. Avoid dry low humidity environments where possible. Blink more often and more fully. Increase omega-3 fatty acid intake (patient already using Scope PRN Omega Eye - 4 capsules a day 2.2g EPA and DHA).
Review period
2 weeks to ensure no adverse response to topical steroid use Full review in 3 months. Written report to GP.
Follow-up findings
The patient reports good compliance and noticed an overall improvement in her symptoms (mirrored by slightly improved SPEED Index score). However, the symptoms of photosensivity during VDU work and the pain in and around her eye remain and are therefore still causing her quite some concern. SPEED index score although improved is still very high.
Clinical examination
Repeat examination (table 2) revealed resolution of the inferior corneal staining, improved meibomian gland expressibility and quality, massively improved NIBUT and TBUT (see figure 7), improvement in tear volume measurements and consistently low conjunctival hyperaemia.
All pain and no stain – Neuropathic Dry Eye
So what options do we have when the patient is still symptomatic despite our best efforts?
Despite a relatively normal clinical picture where the patient has healthy tear volume, healthy tear evaporation rate, healthy meibomian gland output, no visible inflammation, no hyperaemia, no corneal or conjunctival staining, no sign of infection or blepharitis the patient still suffers from severe symptoms. This suggests some form of corneal neuropathic pain with associated neuropathic photosensitivity and a decision was made to manage with scleral contact lenses (full details will appear in the next Contact Lens Monthly).
Discussion
Utilising the holistic approach, albeit an initially time consuming exercise, in patients of this nature is hugely beneficial. Spending the additional time with the patient to ensure that you fully understand the severity of their symptoms and can sympathise and even empathise with them is an important step in their management. Often patients with symptoms of this sort will have been dismissed or ignored by numerous other ECP’s before attending your practice, this can further fuel their feelings of isolation and depression, which in turn are a potential driver of their ocular symptoms. Positively and delicately explaining that the clinical picture looks good despite the severity of their symptoms and further explaining that you have seen and dealt with other patients with similar experiences will be play an important role in successful management of thee difficult cases. As primary care givers ECP’s are well placed to help diagnose patients with depression related symptoms and offer appropriate referral to care pathways via the patients GP.
Using a validated patient questionnaire to quantitatively assess and monitor patients’ symptoms is important in patients with neuropathic pain. Commonly the patients’ symptoms will not correlate well with the clinical exam,125 without the questionnaire it easy for the practitioner to underestimate the extent of the patients’ symptoms and the effect on quality of life. There is vast of array of diagnostic equipment and technology available to help improve our skills as diagnosticians in complex cases of dry eye. As will be discussed next month, scleral lenses may be therapeutically beneficial in the management of patients of this nature where other more conventional treatments have failed.
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Craig McArthur is involved in a dedicated anterior eye clinic service at Peter Ivins Eyecare practice in Glasgow.