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26 Diagnostic Procedures (I): Ocular and Oral Tests

371

Table 26.2 Symptoms evaluation according to the American-European Consensus Group

I. Ocular symptoms: a positive response to at least one of the following questions:

1.Have you had daily, persistent, troublesome dry eyes for more than 3 months?

2.Do you have a recurrent sensation of sand or gravel in the eyes?

3.Do you use tear substitutes more than three times a day?

II. Oral symptoms: a positive response to at least one of the following questions:

1.Have you had a daily feeling of dry mouth for more than 3 months?

2.Have you had recurrently or persistently swollen salivary glands as an adult?

3.Do you frequently drink liquids to aid in swallowing dry food?

26.1Definitions

KCS is defined as a tear deficiency or an excessive tear evaporation that causes damage to the cornea and/or conjunctiva. It may be associated with ocular discomfort secondary to dryness. SS is the prototype of an aqueous deficient dry eye [7]. Symptomatic xerostomia is the subjective feeling of oral dryness [8]. Xerostomia is defined as flow rates £0.1 mL/min.

26.2Questionnaires

Some questionnaires are available to evaluate the presence dry eye. However, most of these questionnaires do not assess symptomatology with sufficient thoroughness [9]. In contrast, the Dry Eye Questionnaire (DEQ) characterizes the frequency of ocular surface symptoms and their diurnal intensity. The DEQ has been validated for the study of KCS [10, 11].

Two questions regarding oral and ocular symptoms are customarily included as items of the current primary SS classification criteria [12] (Table 26.2). These questions yield a sensitivity of 81.4% and 84.9%, respectively, with a specificity higher than 80% [13]. Moreover, the retest reliability of these questions 1 year later are 96.4% and 98.2%, respectively [14]. Nevertheless, the correlation between sicca symptoms and objective signs of glandular dysfunction is only moderate [1, 15]. A precise measure of symptoms, therefore, is an important aspect of making the diagnosis of either dry eyes or dry mouth. With regard to xerostomia, careful inspection of the mouth looking for angular cheilitis, saliva in the mouth’s floor, deep tongue fissures, candidiasis, and atypical caries is useful [5].

26.3Ocular Tests

The tests used most frequently to assess the integrity of the corneal surface and the volume and quality of tear film are the Schirmer-I test (Schirmer test), Rose Bengal staining, fluorescein or lissamine green staining, and the tear break-up time (Table 26.3) [16].

372

 

G. Hernández-Molina et al.

Table 26.3 Methods for evaluating dry eye

 

 

Test

Basis and method

Abnormal test

Reference

SchirmSchirmer-I Measure of tear secretion

£5 mm

[13, 26]

and -II tests

See text for details

Sensitivity 76%

 

 

 

Specificity 72%

 

Break-up time

Index of tear film stability

£10 s

[16]

 

See text for details

Sensitivity 77%

 

 

 

Specificity 38%

 

Vital stains

Stain the ocular surface to

Grading Bijsterveld score ³4

[29, 31, 32]

 

discover abnormalities

 

 

Rose Bengal

See text for details

Sensitivity 78%

 

Lissamine green

 

Specificity 67%

 

Fluorescein

 

 

 

Tear meniscus

Measure of basal tear volume

Normal value 0.3 ± 0.1 mm

[16, 19]

 

with a video meniscometer

 

 

Tear osmolarity

Osmolarity is increased as a

Normal value

[19]

 

result of cytokines’

304 ± 1.4 mOsm/L

 

 

liberation. It is measured

A value ³312 mOsm/L

 

 

with an osmometer

identifies dry eyes

 

 

 

(sensitivity 94%,

 

 

 

specificity 97%)

 

Tear proteins:

Decrease in these proteins is a

Normal value for lysozyme

[17–19]

lysozyme,

reflex of glandular

1–3 mg/mL and for

 

lactoferrin

dysfunction. Measured by

lactoferrin 2 ± 1.1 mg/mL

 

 

immunonephelometry,

Lysozyme specificity 96%,

 

 

agars gels, ELISA,

sensitivity 25%

 

 

spectrophotometry

Lactoferrin specificity

 

 

 

67–90%, sensitivity

 

 

 

78–28%

 

Ferning test

An index of tear film stability.

Uniform and abundant

[20]

 

A freshly produced tear is

arborization (Ferning

 

 

dropped on light micros-

phenomenon) is absent

 

 

copy slides, after

 

 

 

evaporation at room

 

 

 

temperature.

 

 

 

Crystallization is observed

 

 

 

without staining

 

 

Brush cytology

Analysis of conjunctival

Only conjunctival epithelial

[19]

 

morphology. Type and

cells should be found. It

 

 

grade of inflammation

is pathological when

 

 

 

mononuclear cells or

 

 

 

neutrophils are present

 

Imprint cytology

Evaluation of squamous

Score ³2 has a specificity or

[19]

 

metaplasia. It is performed

93% and sensitivity 30%

 

 

under local anesthesia

 

 

 

using cellulose filters.

 

 

 

Score 0 (normal epithe-

 

 

 

lium) to 5 (advanced

 

 

 

keratinization)

 

 

 

 

 

 

26 Diagnostic Procedures (I): Ocular and Oral Tests

373

Rose Bengal staining, once a standard test in this disease, is now used less frequently because the application of the ocular stain is intensely uncomfortable to patients with KCS.

Because gradual destruction of the lacrimal gland in SS leads to diminished levels of tear proteins (lysozyme, lactoferrin, tear-specific prealbumin), some authors have proposed to measure these proteins to identify patients with dry eyes [17, 18]. Other tests, such as the tear film osmolarity, tear evaporation, tear meniscus, and ocular surface impression cytology, and crystallization, have also been studied (Table 26.3) [19, 20]. Although all of these methods provide different qualitative information, they have not achieved general clinical acceptance because of their lack of broad accessibility and general applicability.

26.3.1Schirmer Test

The Schirmer test, a practical, semiquantitative method, is a commonly used initial screening procedure for SS [13]. Some studies have reported a good correlation between in vivo fluorometric measurement of basal tear turnover and tear flow [21], as well as with the rose Bengal test [22]. Other studies, however, have not [23–25].

The Schirmer test may be performed with or without topical anesthetic. In order to assess the maximal tear production, a cotton-tipped swab can be introduced gently into the nose to stimulate the nasolacrimal gland reflex (via the trigeminal nerve) while performing the Schirmer test [26]. This is known as a Schirmer-II test. For some authors, the Schirmer-II test has a better correlation with staining tests [24].

During the Schirmer test, a standardized tear test strip is placed between the eye and the lateral part of the inferior eyelid. The patient is then inclined forward in a resting position at 45°, with eyes closed. After 5 min, the length of the wetted strip area is measured (Fig. 26.1). Humidification of £5 mm at least in one eye is required for a test result to be positive. The sensitivity and specificity of the test are 76.9% and 72.4%, respectively, when this cutoff value is used [13]. When the first test is positive in both eyes, the test-retest reliability at 1 year is 77.4% for one eye and 84.2% for both [14].

One of the factors that influences the results of the Schirmer test is the tear clearance rate. Consequently, a tear function index (TFI) has been proposed as a better tear measurement. The TFI is derived from dividing the Schirmer’s test value by the tear clearance rate, which is calculated by instilling 10 mL of fluorescein into the conjunctival fornix [27, 28]. Although the TFI is theoretically useful, it is not as simple to perform as the Schirmer’s test and is not widely used in clinical practice.

374

G. Hernández-Molina et al.

Fig. 26.1 Schirmer-I test. Patient with absence of tear flow strip humidification after a time interval of 5 min. The lack of tear meniscus is also evident

26.3.2Vital Dyes

Vital dyes are any colored substance that contain auxochromes and are therefore capable of staining tissues. Vital dyes used in the field of ophthalmology have acceptable physiological and toxicological profiles. These dyes are used to detect abnormalities on the ocular surface. Positive staining is usually a relatively late manifestation of tear film disturbances or abnormalities of the ocular surface.

26.3.3Rose Bengal

The Rose Bengal method stains degenerated dead cells and cells that have a tendency to keratinization. Van Bijsterveld created a grading scale that divides the ocular surface into three zones: the nasal bulbar conjunctiva, cornea, and the temporal bulbar conjunctiva [29]. After instillation of the 1% Rose Bengal solution into the conjunctiva and asking the patient to blink one or two times, the intensity of staining of each area is scored. Each section is scored 1 (sparsely scattered), 2 (densely scattered), or 3 (confluent staining), such that a maximum score of 9 can be obtained.

KCS diagnosed when a grading Bijsterveld score ³4 in at least one eye is present (Fig. 26.2) [29]. The evaluation of the conjunctiva and cornea can be determined with an ophthalmoscope, although a more accurate evaluation with a slit lamp outfitted with a cobalt filter is preferred. Solutions of rose Bengal should not be left in the patient’s eye for a prolonged period, as this stain may be irritating and uncomfortable. In addition, it is important to remember that the specificity of the test is poor: Patients with infectious conjunctivitis or chronic, irritative conjunctivitis may also show an increased score [30]. The method has a sensitivity of 64.3% and a specificity of 81.7% [13].

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