Ординатура / Офтальмология / Английские материалы / Ophthalmic Drugs Diagnostic and Therapeutic Uses 5th edition_Hopkins, Pearson_2007

LOCAL ANAESTHETICS 147

Clinical note

Precautions for the use of local anaesthetics:

•Explain to the patient the reason for using a local anaesthetic.

•As with any other drug, it is wise to ask patients whether they have previously had corneal anaesthesia and whether there was any adverse reaction to the drug used. For example, if an ester-linked compound caused a hypersensitive or allergic response, it is appropriate that an amide be used in future.

•On most occasions a single drop produces adequate anaesthesia.

•Ideally, patients should not leave the practice until corneal sensitivity has largely returned to normal, which is usually 15–20 min after instillation of the drops. Within this period, patients should be discouraged from rubbing their eyes.

•Following use of a local anaesthetic, re-examine the state of the cornea.

•Issue a note that states the local anaesthetic used and provides advice on what action patients should take in the event of an adverse reaction.

•If contact lenses are worn, they should not be inserted until 30 min after the instillation of the local anaesthetic.

References

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149

Chapter 10

Stains

Staining agents are some of the most useful diagnostic agents, providing information fairly rapidly without producing a pharmacological effect. Their usefulness lies in their differential staining characteristics. Important clinical information is provided both by the presence and the absence of staining demonstrated by the use of these agents (Table 10.1).

Many dyes and substances have been investigated in the past for their staining properties. Foster (1980) lists 34 chemical substances that have been used for vital staining of the eye, including such marvellous names as magadala red, safranin, brilliant black and Victorian blue. His bibliography contains a reference to the use of fluorescein by M Straub in 1888, which indicates how long ago the principle of vital staining of the eye was established. Today only two stains are in regular use, fluorescein sodium and rose Bengal.

IDEAL PROPERTIES

•Stains should be water soluble because vehicles other than water will be toxic and/or interfere with staining patterns.

•Stains should selectively stain certain cells or structures in the eye.

•They should not stain skin, clothes, contact lenses or any instrument that is likely to come in contact with the eye when the stain is present.

•The effect should be reversible, either as a result of tear flow or by use of an irrigating solution.

•There should be no interference with vision.

•There should be no other pharmacological effect.

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•They should be non-irritant to the surface of the eye.

•They should be non-toxic, especially as one is looking for pathological changes.

•They should be compatible with other stains and any other compound with which they are likely to be used.

Norn (1972a) has laid down an extensive scheme for the testing of dyes for vital staining of the cornea and conjunctiva. In particular, he was concerned how any new stain would fit in with characteristics of existing dyes.

FLUORESCEIN SODIUM

Fluorescein is an orange–red dye that fluoresces in high dilution. As well as being used as a topical stain, it can also be used as an injection for fluorescein angiography. Fluorescein does not actually stain tissues, it merely colours the tear film. The normal corneal epithelium is impermeable to the tear film and substances dissolved in it, because the lipid membranes at the surface of the eye an effective barrier against polar, water-soluble substances. If this barrier is breached then the tear film can gain access to deeper layers. There is a pH difference between the surface and the deeper tissues and this causes a green colour in the area of desquamation.

The factors that affect the fluorescence of fluorescein have been extensively reviewed. The pH of the solution not only influences the absorption spectrum (like any other pH indicator) but also determines the intensity of the fluorescence, which is highest at pH 8, and thus the area of defect is shown up. After gaining access, the fluorescein will diffuse sideways giving a slightly false picture. Defects in the epithelium whether caused by trauma or disease (e.g. dendritic ulcer), are disclosed by the stain.

OPTIMUM CONDITIONS FOR OBSERVATION

OF FLUORESCEIN

For dilute concentrations of fluorescein in an aqueous solution, light with a wavelength between 485 and 500 nm is absorbed maximally. This absorbed energy excites the fluorescein molecules and the emitted light is in a lower energy state and of longer wavelength. The fluorescent light appears green, having its highest intensity at a wavelength between 525 and 530 nm.

To observe the fluorescein pattern of the fit of a rigid lens, contact lens practitioners have commonly used a Burton-type lamp, which is generally fitted with a pair of 4 W ‘blacklight blue’ miniature tubular fluorescent lamps. Wavelengths produced by such a source range from approximately 305–410 nm, with maximal emission at 350 nm. Some hard contact lens materials have been formulated to absorb within the UV-A band of long-wave radiation, which ranges from 315 to 400 nm. As

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Figure 10.1 Applanation tonometry with Goldmann tonometer.

attempt to overcome this disadvantage: Fluorexon (Refojo et al 1972). The use of this dye is limited because, although it will not enter pHEMA (polyhydroxyethylmethacrylate), it stains most other lenses, and even a 4% solution is not as fluorescent as 0.5% fluorescein (Ruben 1978).

Applanation tonometry In applanation tonometry (Fig. 10.1), the visibility of the fluorescein, observed under cobalt-blue filter light, again assumes practical significance. The margin of the applanated area is delineated by a solution of the dye; the ‘touch’ area (purplish-black) has a diameter of 3.06 mm on the cornea. The concentration of the fluorescein is very important in this technique and it should not be too low (as occurs with excessive tearing), when the examiner’s visibility of it is impaired, or too high. The best results are often obtained when using benoxinate hydrochloride 0.1% as the local anaesthetic, as recommended by Goldmann. A 2% solution of fluorescein is far too strong for this procedure. Grant (1963) suggests a 0.25% concentration and, with experience, just the right amount may be obtained by employing sterile fluorescein paper strips.

Because Goldmann-type applanation tonometers involve contact with the eye, a topical anaesthetic has to be administered with the fluorescein. Unfortunately, local anaesthetics are salts of weak bases and strong acids. Sodium fluorescein is a salt of strong base and weak acid. Mixtures of the two types of compound are thus inherently unstable. A stabilized mixture of lidocaine (4%) with fluorescein (0.25%) is available in singleuse units. If benoxinate is the preferred anaesthetic, it should be instilled separately or used to moisten the fluorescein strip. For a full description of the technique of accurate applanation measurements of intraocular

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pressure, the reader is referred to the appropriate literature issued with the instrument, and such papers as those of Grant (1963), Moses (1960) and Spaeth (1978). Considerable practice and experience are necessary before reliable results are routinely obtained, and visual field examinations should always be conducted, whenever possible, in conjunction with Schiotz or applanation tonometry.

Lacrimal patency To demonstrate the patency of the lacrimal drainage system in patients complaining of frequent and troublesome epiphora, a drop or two of 2% fluorescein sodium eyedrops (P) can be used. Alternatively, a salinemoistened fluorescein strip can be used to convey sufficient amounts of the dye to the conjunctiva. Then a few drops of saline solution are also instilled into the conjunctival sac to increase the volume of liquid present and patients are asked to blow their nose in a white tissue. Yellow staining of the tissue proves patency of the lacrimal drainage of this particular eye; the procedure is repeated for the other. Absence of staining of the tissue does not necessarily indicate obstruction to the passage of tears down the lacrimal passageway until observation has shown that the lacrimal punctum is in correct apposition to the globe of the eye.

Tear flow assessment The half-life of drops in the conjunctival sac is very short. It will depend on the patency of the nasolacrimal duct and the rate of tear production. The rate at which fluorescein disappears from the conjunctival sac can be taken as a measure of the tear flow. Barendsen et al (1979) used fluorescein to estimate the minimum permissible interval between the application of drugs. Predictably, they found that fluorescein concentration in the tear film decreased faster in younger patients and thus viscous solutions were cleared at a slower rate than aqueous ones.

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CONTAMINATION

Contamination of fluorescein eyedrops is a particularly serious risk, even greater than that encountered with the majority of other eyedrops. As these individual drops are liable to become infected with bacteria and, at the same time, are frequently used on damaged tissue that is prone to infection, very great care must be taken in their use. Ps. aeruginosa is an especially dangerous pathological microorganism with which fluorescein eyedrops are inclined to become invaded. Phenylmercuric acetate or nitrate in 0.002% strength is the best bactericide for preserving these particular eyedrops, and this is effective against Pseudomonas, given adequate contact time. However, the safest method of their employment is sterile single-dose units or sterile fluorescein-impregnated paper strips, both of which are readily available and to be highly recommended.

ROSE BENGAL

Rose Bengal is a brownish-red powder that is soluble in water and is normally used as a 1% solution. Although not approved for sale in the UK, rose bengal strips have been prepared. This substance is a derivative of fluorescein but has markedly different staining characteristics, crossing the cell membranes of dead cells but not living ones. Mucus threads will also be stained. Some practitioners prefer to examine the eye after rose Bengal staining with a green light.

Rose Bengal also differs from fluorescein in its usage. While probably no optometric practice is without ophthalmic fluorescein in some form, rose Bengal is comparatively little used. This is most likely due to:

(1) the initial irritation to the surface of the eye (especially, unfortunately, patients with dry eyes); and (2) unfamiliarity with the results of staining. It is useful in the following conditions.

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MIXTURES OF FLUORESCEIN AND ROSE BENGAL

A mixed stain containing 1% fluorescein sodium and 1% rose bengal was investigated by Norn (1964b, 1967), who concluded that it was better than the individual stains alone. He examined normal patients, patients with diseases of the cornea, conjunctiva and lacrimal passages and contact lens wearers. For the latter, he concluded that these vital stains are suitable for assessing damage in relation to the wearing of contact lenses. He observed a punctate red crescent on the lower bulbar conjunctiva but considered that modification was indicated only in the presence of symptoms.

Triple staining with the above mixtures plus alcian blue has also been examined (Norn 1964a). The three dyes stain different structures: fluorescein stains epithelial lesions, rose bengal stains degenerate cells and alcian blue stains mucus.

LISSAMINE GREEN B

Lissamine green B fulfils a similar role as a stain as that of rose bengal. For example, it stains lipid-like structures such as mucus strands heavily contaminated by lipids, dead or dying epithelial cells and will stain the leading edges of viral proliferation of a dendritic ulcer while fluorescein tends to stain its central bed. However, rose bengal exhibits significant antiviral effects against herpes simplex virus, which limits its utility in the diagnosis of epithelial keratitis if used before a viral culture has been performed. By contrast, lissamine green B does not possess significant antiviral activity (Stroop et al 2000).

A comparative study has shown that lissamine green B 1% is better tolerated than rose bengal 1% by patients and is equally as effective as rose bengal in evaluating the ocular surface in keratoconjunctivitis sicca (Manning et al 1995). It has also been shown that rose bengal adversely affects corneal epithelial cell viability and stains normal proliferating cells in contrast to lissamine green B, which exhibited neither of these characteristics. It was recommended by the authors of that study that lissamine green B should be recommended in place of rose bengal when evaluating ocular surface disorders (Kim & Foulks 1999).

It is helpful to wait for about 1 min after instillation of lissamine green B before looking for staining with either white or blue illumination on the slit-lamp miscroscope.

It is disappointing that lissamine green B is not currently available in the UK but it is used by practitioners in countries such as the USA in the convenient form of impregnated sterile paper strips.

OTHER STAINS

The following stains are seldom used but nevertheless are of interest:

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Alcian blue A complex copper-containing compound used in 1% solution and specific for staining mucus. Alcian blue is used to counterstain rose bengal, which, in addition to staining dead cells, also stains mucus (Norn 1972b). If a break in the integrity of the epithelium exists, the exposed deeper layers will be stained a pale blue–green colour, which will persist for several months (Norn 1964b).

Clinical note

The following precautions should be observed when using stains:

•When an impregnated strip is used as the source of fluorescein, it should be moistened with sterile saline and any excess shaken off before gentle application to the bulbar conjunctiva.

•Care should be taken not to splash either stain on the patient’s face or clothing.

•To avoid discoloration, soft lenses must be removed prior to the use of either stain. After the use of fluorescein, for example, they can be re-inserted, having irrigated the eye and when the stain can no longer be seen upon re-examination with the slit-lamp microscope.