As has been previously outlined in parts one to five of this series, dry eye disease (DED) is a common but complex, multifactorial spectrum of disorders. DED can cause symptoms from mild irritation to severely debilitating reduction in quality of life which can lead to depression. While it can be sub-divided in a number of ways, traditionally it is divided into reduction in tear quality in the form of evaporative dry eye (EDE) or reduction in tear volume in the form of aqueous deficiency dry eye (ADDE). However, due to the complexity of the condition, presenting patients should be examined in a systematic manner to elicit an accurate diagnosis and rule out comorbidity. The optimal order of examinations has been delineated previously in this series.

This article will highlight examinations which may be useful in diagnosing ADDE, and offers a case history of one such patient and how we managed her case.

Examination Techniques – Evaluating Tear Secretion

As eye care professionals, our diagnostic armamentarium contains several methods that can be used to measure tear volume and detect abnormalities.1-3 These include tear meniscus height,4-6 tear osmolarity,7-9 the phenol red thread (PRT) test10-12 and the Schirmer Test.13,14

The Schirmer test

The Schirmer test has long been considered one of the most common methods to evaluate tear volume in clinical practice since its introduction in 1903.15 The test involves the simple process of hooking a sterile strip of filter paper over the lower eye lid. The strip is kept in place for five minutes and then gently removed. The wetted portion of the strip is measured and recorded. A diagnostic cut-off value of 10mm in five minutes has been suggested, with a test specificity of 67.9% and sensitivity of 82.7%.16

Despite its relative ease of use the technique has several disadvantages including patient discomfort, low reproducibility, long testing time of five minutes, difficulty of use in children and the issue of reflex tearing potentially skewing the results. It is ultimately uncertain exactly what the Schirmer test is measuring as the test paper absorbs the tear fluid as it is produced, but also absorbs the tears residing in the eye as the test paper is first applied. The result is that both production and initial volume contribute to the test results. This issue is further compounded by the fact that the test strip causes significant reflex lacrimation, meaning it is impossible to separate the basal lacrimal production rate from the lacrimal system’s ability to produce reflex tears.

Efforts have been made to improve the procedure including changing the type of filter paper, however no significant improvement was achieved.17,18 Performing the test under local anaesthesia to reduce reflex tearing and improve patient comfort has also been explored, however a degree of reflex tearing was still recorded.19-21

Phenol Red Thread Test (PRT)

The PRT test was introduced in 1983 as an alternative to the Schirmer test.22 The test uses a cotton thread treated with phenol red pH indicator.23 The thread changes colour from yellow to light red when moistened by the alkaline tears (pH 7.4). A 3mm length of the thread is folded and inserted one third distance from the temporal canthus of the lower eyelid, with the eye in primary position. The subject is asked to close his/her eyes for the duration of the test. The thread is then gently removed after 15 seconds and the red-coloured portion of the thread assessed and determined in millimetres. A diagnostic cut off value of 10mm in 15 seconds has been defined as dry eye.24 The test has a sensitivity of 86% and specificity of 83%.25

Despite several obvious advantages over the Schirmer test including shorter testing time of 15 seconds, vastly improved patient comfort and tolerability, no topical anaesthetic required and higher test sensitivity, it is again unclear what the PRT test is measuring.26 It is thought that the PRT test measures the residual tears existing primarily in the inferior conjunctival sac, with minimal effect on the secretion rate of the lacrimal gland.20 However, the wetting observed could have contributions from both tear production and tear volume in the eye.21

Tear Meniscus Height

Numerous techniques have been suggested and developed to assess the tear meniscus height including the use of a slit-lamp with an eye-piece graticule, use of fluorescein to aid visualisation,27 optical coherence tomography,28 optical pachymetry29 and various videos systems.30

Around 85-90% of the total volume of the tears reside in the upper and lower tear menisci.31 Using a slit-lamp biomicroscope to estimate tear meniscus height is the simplest and most common method used in clinical practice. This method suggests a mean meniscus height of between 0.25mm32 to 0.35mm33 in the normal population. A diagnostic value below 0.25mm has be suggested for the diagnosis of dry eye.34,35 The major disadvantage of this technique is the inherent subjectivity of the technique, which in turn induces significant inter-observer variability.36 As a result it has been suggested that each clinician establish their own values for normal patients and dry eye sufferers.

Tear Osmolarity

Tear osmolarity has been suggested as a key driver for normal homeostasis in tear film dynamics.37 Elevated tear osmolarity is known to be a central pathogenic cause of ocular surface and nerve damage,38 and has been regarded by some to be medically necessary to assist in the diagnosis of DED.39 Measurement of tear osmolarity may also be necessary to fully understand the severity of dry eye.40 Measurement of tear osmolarity is considered to be an effective objective test that can be used effectively in the diagnosis of dry eye, regardless of the aetiology of the condition and gauge its severity.41-43 Osmolarity values above 308 mOsms/L are indicative of dry eye disease.44 Commercially available products including the i-Pen and the TearLab Osmolarity System measure tear osmolarity by sampling a small amount of the tear film (around 50nL) from the lateral inferior tear meniscus.

Case history

This case history aims to highlight the interplay between tear volume and tear evaporation in a complex aqueous deficient dry eye patient.

History and symptoms: A 74-year-old female attended at the request of her GP complaining of red, gritty and irritable eyelids. She reports mild photophobia and intermittent blurred vision which is significantly affecting her quality of life and work as a professional artist. She also reports symptoms of xerostomia (dry mouth). She has been using baby shampoo to bathe her eyelids twice per day and hypromellose eye drops for around 12 months with no improvement in her symptoms.

Past ocular health: Bilateral pseudophakia.

Family ocular health: Both parents myopic. Age-related cataracts.  

General health: Rheumatoid arthritis, hypertension, hypercholesterolemia.

Medications and supplements: Macushield. Simvastatin. Ramapril. Hydroxychloroquine. Methotrexate.

Refraction and visual acuity:

    R: -1.00 / +0.50 X 173 6/7.5+ Add: +2.50 (N5)

    L: -1.00 / +1.00 X 179 6/7.5- Add: +2.50 (N5)

Examinations

Pupil reactions: Normal

Oculomotor balance: Mild near exophoria.  Well controlled  

Visual field analysis: Normal

IOPs: R: 21mmHg L: 21mmHg (Using Goldmann applanation Tonometry 10.15am)

CCTs: R: 531µm L: 547µm  

Posterior pole:     

    Right Eye: Unremarkable

    Left Eye: Unremarkable

OSDI questionnaire score: 85 (severe)

Initial differential diagnosis:

  • Aqueous deficient dry eye
  • Evaporative dry eye
  • Neuropathic dry eye
  • Demodex Blepharitis due to presence of rosacea

Clinical Assessment

Anterior Eye Examination

Figure 1: Right eye – lids and adnexa

Figure 2: Left eye – lids and adnexa

Figure 3: Right eye – external eye

Figure 4: Left eye – external eye

Figures 1-4 show the external eye both open and closed. Results of the slit-lamp examination are summarised in table 1. Moderate meibomian gland dysfunction was noted with around 50% of meibomian glands expressing meibum, mostly cloudy in appearance. Telangiectasia was noted on the lid margin and closed upper eyelid. However, the lids were otherwise healthy and devoid of significant scarring or pitting. The lid margin and eye lashes were clean and devoid of matter. Mild conjunctival and limbal hyperaemia was noted.

Figures 5 and 6 reveal the extent of corneal staining (left eye worse than the right) and poor tear evaporation rates.

Figure 5: Right eye – fluoroscein staining

Figure 6: Left eye – fluoroscein staining

Tear evaporation measurement

Tear evaporation was measured at  4.0 seconds in the right eye and 3.0 seconds in the left during slit-lamp; assessment aided with fluorescein. Objective non-invasive tear breakup time (NIKBUT) using an Oculus K5 revealed initial evaporation rates of 6.88 seconds in the right eye and 4.63 seconds in the left eye – results shown in figures 9 and 10.  

Figure 9: Right eye – objective NIKBUT

Figure 10: Left eye – objective NIKBUT

Tear volume measurement

Tear meniscus height measured using fluorescein and slit-lamp biomicroscope measured at 0.2mm in both eyes. Non-invasive tear meniscus height measurements achieved again using an Oculus K5 measured at 0.2mm in the right eye and 0.15mm in the left eye, results shown in figures 7 and 8.

Figure 7: Right eye – objective tear volume

Figure 8: Left eye – objective tear volume

Meibography

Meibography reveals significant shortening of meibomian glands and some localised atrophy and gland drop-off. This is in keeping with chronic meibomian gland dysfunction.

Figure 11: Right eye – meibographyFigure 12: Left eye – meibography

Diagnosis

The results of the patient’s eye examination are concisely summarised in the Jenvis Report shown in figure 13. The severity of the patients’ symptoms, history of rheumatoid arthritis, low tear volume, significant corneal staining, poor tear evaporation times and meibomian gland dysfunction are suggestive of keratoconjunctivitis sicca with both ADDE and EDE components potentially secondary to Sjögren’s syndrome.

Figure 13: – Jenvis Dry Eye Report

Management

Due to the severity of the patient’s symptoms the initial treatment was aimed at reducing inflammation and increasing the patients comfort.

Initial treatment plan:

  1. Oral Doxycycline 100mg for three months
  2. Anti-inflammatory therapy – FML topical steroid eye drops on a 4/3/2/1 basis over a four-week period
  3. Eyelid therapy at home – heat, lid massage and hygiene via an MGDRx eye bag and Thera Tears Sterilid foam twice per day
  4. Preservative free artificial tears with lipid component – Emustil eye drops four times per day
  5. Preservative free gel before bed – Thealoz Duo Gel
  6. Referral to rheumatology for Sjögren’s testing
  7. Referral to ophthalmology for consideration for autologous serum eye drops

Treatment plan after three months:

  1. Preservative free artificial tears with lipid component – Emustil Eye Drops four times per day
  2. Preservative free gel before bed – Thealoz Duo Gel
  3. Omega III dietary supplement – Omega Eye from Scope Medical four times per day
  4. Punctal occlusion – Intracanalicular punctal plugs (see figures 14 and 15)

Figure 14: Right eye - punctual plug before full insertion

Figure 15: Left eye - punctal plugs before full insertion

Outcome

A significant improvement in patient symptoms, OSDI score and resolution of corneal staining was achieved within six months using the treatment planned outlined above. A significant improvement in tear meniscus height was achieved as shown in figures 16 and 17, from 0.2mm to 0.46mm in the right eye, and from 0.2mm to 0.42mm. Similar levels of improvement in non-invasive tear break-up time were also achieved from 6.88 seconds to 9.94 seconds in the right eye, and from 4.63 seconds to 9.75 seconds in the left eye, shown in figures 18 and 19.

Figure 16: Right eye – objective tear volume (after treatment)

Figure 17: Left eye – objective tear volume (after treatment)

Figure 18: Right Eye – NIKBUT (After Treatment)

Figure 19: Left Eye – NIKBUT (After Treatment)

Partial and temporary punctal occlusion via lower lid absorbable synthetic intracanalicular implants replaced on a three-monthly basis (as shown in figures 14 and 15) in conjunction with use of autologous serum supplied by our local ophthalmology department is currently maintaining a happy patient.

Lacrimal Drainage Occlusion

Blocking tear outflow from the eye is appropriate for a small percentage of patients and is mainly reserved for patient with ADDE where retention of fluid, whether natural or via artificial tears, in the interpalpebral area is desirable. It is not suitable in patients with active lid margin disease due to tear stasis and subsequent increased risk of infection.

Many surgical and thermal options are used within secondary care to achieve lacrimal occlusion including canalicular ligature, canaliculotomy, relocation of the punctum to a position out of the tear meniscus, punctal tarsorrhaphy, the punctal patch, cautery, diathermy and argon laser photocoagulation.

Punctal and intracanalicular occlusion can provide short-term, medium term and long-term occlusion. Their use falls within the skillsets of the community based optometrist. Punctal occlusion can significantly improve the quality of life in appropriate patients suffering from moderate to severe dry eye. There is an extensive range of products commercially available and excellent training available from manufacturers and distributors to help aid practitioners new to this area. Punctual occlusion has been shown to decrease dependency on tear supplements,45 decrease tear osmolarity,46 increase tear volume,47 decrease ocular surface staining,48 increase goblet cell density,49 increase tear film stability and subjectively reduce patient symptoms.50

It is important however that practitioners are aware of not only the benefits but the risks and complications of punctual plugging.  Careful patient selection is crucial for the procedure to be successful and it should only be conducted when appropriate.  Com-plications can include damage to ocular surface, perforation of the canaliculus,51 loss of plug below punctum,52 epiphora, ocular irritation, infection,53 pyogenic granuloma development,54 spontaneous canalicular mucosal dissection and punctal stretching.55

Autologous Serum

Autologous serum is typically manufactured by centrifugation of the peripheral blood followed by dilution in artificial tears or saline. Autologous serum drops were first used clinically in the 1970s to help treat ocular alkali burns.56 Use of the autologous serum drops in the treatment of dry eye was first described in the literature in 1984,57 however it was not until the 1990s that its use became more widespread.58,59 It is used to treat a variety of conditions including dry eye, dry eye-related disorders such as Sjögren syndrome, persistent epithelial defects, neurotrophic keratopathy, recurrent corneal erosion, superior limbic keratoconjunctivitis, ocular cicatricial pemphigoid, graft-versus-host disease and Stevens-Johnson syndrome.60 Despite having been shown to be a safe and effective treatment, it is not used routinely in part due to potential risk of infection, lack of availability, inconvenience and most importantly cost.

Discussion

As a profession, we have an ever-growing list of diagnostics tests, techniques and equipment at our disposal, in conjunction with an ever-expanding list of potential treatment options for dry eye and dry eye-related conditions. We are ideally situated as primary care givers to tackle a large percentage of dry eye suffers that walk through our doors, saving the patient the time and anxiety involved in visiting a hospital eye clinic. With a carefully planned, systematic approach to our clinical examination and patient history, coupled with the zeal to embrace new diagnostic techniques and treatments for dry eye we should be able to simultaneously ease the burden of the patient, our colleagues in already over-stretched ophthalmology departments and build a thriving and profitable optometric practice. In the next instalment of this series we will explore the dry eye patient journey and how a dry eye clinic can be used to grow your patient database and increase practice profitably. 

Craig McArthur is involved in a dedicated anterior eye clinic service at Peter Ivins Eyecare practice in Glasgow.

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