Diagnostic Procedures in Dry Eyes Syndrome 405

406Diagnostic Procedures in Ophthalmology

of keratin in the orifices), reduced expressibility of meibomian gland secretions and turbid or thick toothpaste like secretions of the meibomian glands. The presence of thickening of the lid margins, telangiectatic blood vessels and cysts on the lid margin may be noted. Transillumination may also reveal drop out of the meibomian gland ducts, which is a sign of obstructive meibomian gland disease. In patients with acne rosacea with inflammatory meibomitis, the gland architecture is distorted. Video meibography, using one-chip infrared video camera and a hand held transilluminating light source along with a video monitor, is useful for imaging the abnormal structure of the meibomian glands in chronic blepharitis.

Clinical Diagnostic Tests for Dry Eyes

Tear Film Break-Up Time (TBUT)

According to the diagnostic algorithm put forth by Plugfelder3 for diagnosing dry eye, fluorescein tear break-up time (TBUT) is the first diagnostic test to be done which gives information regarding tear film stability. A diagnosis of tear film instability is made when a fluorescein TBUT value of <10 seconds is obtained. Even though Decker in 1876 started research on tear film stability, it was Norn4 in 1965 who evolved a simple and convenient method to assess the tear film stability by observing the tear film using a cobalt blue filter on a slit-lamp, after instilling fluorescein stain. The interval between the last blink and the first appearance of a dry spot on the fluorescein-stained tear film was then called the corneal wetting time. Later term break-up time or tear break up time (BUT or TBUT) was used.5-7 Although different methods now exist like the invasive5 and non-invasive methods2, difference in the method of instilling fluorescein, number of readings taken4-6,8 and the type of slit-lamp

observation, with a narrow vertical slit, horizontal slit or a full beam9, 10, this test is of importance ever since it has been identified as the screening test in determination of dry eyes in the potential contact lens wearers.7

The clinical method of doing fluorescein tear break-up time (TBUT) is as follows:

The subject is made to sit comfortably on a slit-lamp with forehead firmly against the forehead rest and chin resting comfortably on the chin rest. The microscope is positioned directly in front of the eye to be receiving the stain. The fluorescein strip is wetted with a drop of preservative-free saline. The strip is then applied over the inferotemporal conjunctiva. The subject is asked to blink for 3-5 times only and then is asked to stop blinking. The fluorescein staining is then viewed under a slit-lamp (full beam) using a blue filter along with a wratten filter with magnification. The time interval from the last blink to the appearance of a randomly seen dark spot is recorded with a stopwatch. This is followed by taking another 2 readings of TBUT with a gap of 3-5 blinks in between.

Non-invasive break-up time (NIBUT): In this method, mire is projected using a keratometer, topography, perimeter or tearoscope. The time taken for the tear film to distort or break-up after a blink is measured. The reading of break-up time is less than that of invasive tear break-up time using fluorescein, but it is more difficult practically to do it in the clinic.

Schirmer’s Test 1 without Anesthesia

This test assesses the reflex secretion and tear production potential. No anesthetic is used. Whatman filter paper #41 measuring 35 mm in length with a bend at 5 mm is used, and placed at the junction of medial 2/3 and lateral 1/3 of the lower lid in the fornix (Fig. 25.1). The patient is asked to look forward and blink

Fig. 25.1: Schirmer’s test showing the Whatman filter at the junction of medial 2/3rd and lateral 1/3rd of lower lid in the fornix

normally. The test is carried out in dim illumination and under standard conditions of temperature and humidity. The length of wetting is recorded after 5 minutes. Wetting of less than 5 mm is considered abnormal.

Schirmer’s Test with Anesthesia

Topical proparacaine is instilled into the conjunctiva. After 5 minutes, the excess fluid is wiped off with a Johnson’s bud. The fluorescein strip is then placed as mentioned above and the length of wetting is read after 5 min. While taking the reading when the front of the wetted area was uneven, the millimeter it crosses is recorded as the value.

Schirmer’s test though categorized by many researchers as non-reliable11-14 is still widely used to assess adequacy of tear production15-19 to help in diagnosis of keratoconjunctivitis sicca, screening for dry eye in contact lens wearers12,20 and for analysis of chemical components of tear film.21-23 Lemp in the workshop on clinical trials of dry eyes puts forth the use of Schirmer’s test as the standard measure for diagnosing teardeficient dry eye. Validated by van Bijsterveld,24 this test is also recommended by the working group on diagnostic tests, and available for routine clinical practice.

Diagnostic Procedures in Dry Eyes Syndrome 407

Schirmer’s Test with Nasal

Stimulation

After performing routine Schirmer’s test, a cotton swab is inserted into the nasal cavity towards the direction of ethmoid sinus. A 75 mm strip of Whatman filter paper #41 is placed in the conjunctival fornix and the length of wetting measured after 5 minutes. Wetting of less than 10 mm is considered abnormal. It is advisable to perform this test on a different occasion. Patients, who do not respond to nasal stimulation by an increase in the lacrimal secretion, are thought to have an invasion of lymphocytes into their lacrimal glands,5 resulting in anatomic destruction of the gland. Such patients do not show any response even on maximal stimulation. Patients who respond, the lacrimal gland is viable. When patient responds to nasal stimulation but is less responsive to conjunctival stimulation, it is postulated that the reflex circuit between the lacrimal gland and the conjunctiva is disturbed.

Diagnostic Dye Staining: Fluorescein and Rose Bengal Stain

The instillation of dyes is a common method to detect ocular surface epithelial pathology associated with dry eyes. Rose bengal is a fluorescein derivative that has been used for the diagnosis of dry eye since Sjögren25 described the presence of dye staining in patients with keratoconjunctivitis sicca (KCS) in 1933. It was thought to stain only devitalized epithelial cells but it also stains healthy epithelial cells when they are not protected by a healthy layer of mucin.26 Therefore, it has the unique property of evaluating the protective status of the preocular tear film. Rose bengal also stains dead or degenerating cells, lipid-contaminated mucous strands, and corneal epithelial filaments (Fig. 25.2). Solution is preferred over impregnated

408 Diagnostic Procedures in Ophthalmology

Fig. 25.2: Diffuse slit-lamp view showing rose bengal staining (arrow) in a patient with aqueous tear deficiency (ATD)

strips.27 A double vital staining technique was described at the NEI Workshop.1 A 2 μl mixture of 1% rose bengal and 1% fluorescein (preser- vative-free) and non-preserved saline without anesthetic, is instilled into the conjunctiva. The areas of staining are graded on slit-lamp examination.

The interpretation of rose bengal staining in dry eyes is based on two factors, intensity and location. Van Bijsterveld 28 reported a grading scale that evaluates the intensity based on a scale of 0 to 3 in three areas: nasal conjunctiva, temporal conjunctiva and cornea, with a maximum possible score of 9. The classic location for rose bengal staining in aqueous tear deficiency is interpalpebral conjunctiva, which appears in the shape of two triangles whose bases are at the limbus. The NEI workshop has recommended division of nasal and temporal conjunctiva into 3 zones, each graded from 0-3, with a maximum possible score of 18.

Rose bengal staining is considered more sensitive and more specific in detecting patients with dry eyes than either reduced tear breakup time or a low Schirmer’s test. Rose bengal staining may help to differentiate between ATD and lipid tear deficiency (LTD) by studying the distribution of stain in the non-exposure zone.

Fig. 25.3: Diffuse slit-lamp view showing fluorescein staining with filaments in a dry eye patient

Preferential staining has been observed in nonexposure zones in the LTD, whereas in ATD, the staining is seen in the exposed interpalpebral areas.29

Fluorescein is another diagnostic dye commonly used for diagnosis of dry eye. The dye penetrates intercellular spaces and indicates increased epithelial permeability.26 Fluorescein generally stains the cornea more than the conjunctiva (Fig. 25.3).

Lissamine green B has been investigated as a marker for ocular surface disease. It is found to detect dead or degenerated cells and it produces less irritation after topical administration than rose bengal.

Fluorescein Clearance Test

Schirmer’s Strip

Ten microlitre of 0.5% fluorescein and 0.4% oxybuprocaine hydrochloride are instilled into the conjunctival fornix. The eyes are kept open for 5 minutes. 35 mm long strips of Whatman filter paper #41 is placed in both the eyes. The eyes are then closed for 5 minutes. The intensity of color is compared to a standard scale. Each grade shows a 12.5% increase in the basal tear turnover and tear flow. This method may not

reflect the basic tear secretion since reflex tearing may occur in response to the slit-lamp illumination or irritation by the strip. The length of wetting may affect the intensity of fluorescein color on the strip. In general the darker the color of fluorescein, the less or poor is the clearance.

Visual Scale

This is a safe and inexpensive method that

Diagnostic Procedures in Dry Eyes Syndrome 409

corroborates with irritation symptoms. Six microlitre of 2% fluorescein is instilled into the inferior cul-de-sac. Fifteen minutes later, the color of the lower tear meniscus at the lateral 1/3 of lower lid is compared with the standardized scale (3 = Normal, >3 = disease, <3 = equivocal).

A simple diagnostic algorithm is given below to place a given patient in one of the categories of dry eyes.

410Diagnostic Procedures in Ophthalmology

Laboratory Tests

Tear Film Osmolarity

Tear film (TF) osmolarity is said to represent the gold standard in the diagnosis of DE because of its greater sensitivity and specificity as a single test or in combination with other tests. Though, it is unable to distinguish between ATD DE and Evaporative DE. The osmolarity of basal tears is measured and thus reflex tearing has to be avoided. There exists a need for an instrument that is more reliable and freely available for testing TF osmolarity. Technical errors resulting in falsely abnormal values are reported.

Tear Ferning

Conjunctival mucus from a normal eye crystallizes in the form of ferns when placed on a dry glass slide and observed under the microscope. The scrapings are obtained from lower nasal palpebral conjunctiva, 30 immediately following drying; the slide is evaluated under a microscope to find typical mucus arborization or ferning. Ocular ferning test from conjunctival scrapings is considered as a quantitative test for mucin deficiency. The conjunctival mucus may be reduced or absent in those patients with conditions like chemical burns, ocular cicatricial pemphigoid and Stevens-Johnson syndrome.

Conjunctival Impression Cytology

The surface of the normal conjunctiva contains goblet cells that produce mucin. In cases of advanced dry eye, the epithelium undergoes pathologic changes, termed squamous metaplasia, and the density of goblet cells decreases. As a result, the tear film becomes unstable secondary to a reduction in the mucin layer of the tear film. Conjunctival impression cytology allows the evaluation of epithelium and goblet cells on the conjunctival surface.

Lysozyme and Lactoferrin Assays

Though lysozyme and lactoferrin are found to be low in dry eye, the tests for their evaluation are cumbersome and expensive and hence not recommended for use in clinical practice.

Measurements of Immnoglobulins and Antibodies

Measurements of IgA, IgG, IgM and viral antibodies 31 in tears by ELISA have been tried as laboratory tests in the diagnosis of dry eyes. Since constitutive protein concentration in the tears varies with flow rate, tear collection must be standardized and it has to be assured that only non-stimulated tears are obtained.32

Serum Autoantibodies

Detection of serum autoantibodies is used to diagnose Sjögren’s syndrome ATD. One or more of the following autoantibodies may be found: Antinuclear antibodies (ANA titer ≥1:160), rheumatoid factors (RF titer ≥1:160) or Sjögren’s syndrome–specific antibodies such as anti-Ro (Sjögren-A) or anti-La (Sjögren-B). In one study33 antinuclear antibodies (ANA) were the most frequently detected antibodies in ATD being present in 80%. In contrast, positive RF was found in 65% and positive SS-A in 30% of the same group of patients.34

References

1.Lemp MA. Report of the National Eye Institute/ Industry Workshop on Clinical Trials in Dry Eyes. CLAO 1995;21:221-32.

2.Tabbara KF, Wagoner MD. Diagnosis and management of dry eye syndrome. Int Ophthalmol Clin 1996;36:61-76.

3.Pflugfelder SC, Tseng SCG, Sanabin O, et al. Evaluation of subjective assessment and objective diagnostic tests for diagnosing tear film disorders known to cause ocular irritation. Cornea 1998;17:38-56.

4.Norn MS. Desiccation of precorneal film. I Corneal wetting-time. Acta Ophthalmol (Kbh) 1969;47:865-80.

5.Lemp MA, Hamill JR. Factors affecting tear film break up time in normal eyes. Arch Ophthalmol 1973;89:103-05.

6.Rengstorf RH. The precorneal tear film break up time and the location in normal subjects.

Am J Optom Physiol Opt 1974;51:765-69.

7.Holly FJ. Tear film physiology and contact lens wear. II. Contact lens tear film interaction. Am J Optom Physiol Opt 1981;58:331-41

8.Vanley GT, Leopold IH, Gregg TH. Interpretations of tear film break up. Arch Ophthalmol 1977;95:445-48.

9.Cho P, Brown B. Review of TBUT technique and a closer look at the TBUT of HK-Chinese. Optom Vis Sci 1993;70:30-38.

10.Cho P, Brown B, Chan I, Conway R, Yap M. Reliability of the tear film break up technique of assessing tear stability and the locations of tear break up in Hong Kong Chinese. Optom Vis Sci 1992; 69:879-85.

11.Wright JC, Meger GE. A review of Schirmer’s test for tear production. Arch Ophthalmol 1962;67:773-82.

12.Tabak S. A Short Schirmer’s test. Contacto 1972;16(2):38-42.

13.Hanson J, Fikentscher R, Rosenberg B. Schirmer’s test of lacrimation. Arch Ophthalmol 1975;101:293-95.

14.Henderson JW, Prough WA. Influence of age and sex on flow of tears. Arch Ophthalmol 1950;43:224-31.

15.Mishima S, Gasset A, Klyce SD, Baum JL. Determination of tear volume and tear flow. Invest Ophthalmol 1966;5(3):264-76.

16.Jones LT. Lacrimal secretory system and its treatment. Am J Ophthalmol 1966;62:47-60.

17.Shapiro A, Merin S. Schirmer test and break up time of tear film in normal subjects. Am J Ophthalmol 1979;88:752-57.

18.Hamano H, Hori M, Hamano T, Mitsunaga S, Maeshima J, Kojima S, Kawabe H, Hamano T. A new method for measuring tears. CLAO J 1983;9:281-89.

19.Rajiv, Mithal S, Sood AK. Pterygium and dry eye – a clinical correlation. Indian J Ophthalmol 1991;39:15-16.

Diagnostic Procedures in Dry Eyes Syndrome 411

20.Clinch TE, Benedetto DA, Feldberg NT, Laibson PR. Schirmer’s test: a closer look. Arch Ophthalmol 1983;101:1383-86.

21.Prause JU. Immunoelectrophoretic determination of tear fluid proteins collected by the Schirmer I test. Acta Ophthalmol (Kbh) 1979; 57:959-67.

22.Kiljstra A, Jeurissen SHM, Koning KM. Lactoferrin levels in human tears. Br J Ophthalmol 1983;67:199-202.

23.Stuchell RN, Feldman JJ, Farris RL, Mandel ID. The effect of collection technique on tear composition. Invest Ophthalmol Vis Sci 1984; 25:374-77.

24.Van Bijsterveld OP. Diagnostic tests in the sicca syndrome. Ann Ophthalmol 1969;82:10-14.

25.SjögrenHS.Zurkenntnisderkeratoconjunctivitis sicca (keratitis folliformis ber hypofunktion der ranendrasen). Acta Ophthalmol (Copen) 1933; 11:1-151.

26.Feenstra RPG. Tseng SCG. Comparison of fluorescein and rose bengal staining. Ophthalmology 1992;101:984-93.

27.Roberts DK. Keratoconjunctivitis sicca. J Am Optom Assoc 1991;62:187-99.

28.Van Bijsterwald OP. Diagnostic tests in the sicca syndrome. Ophthalmology 1969;82:10-14.

29.Lee SH, Tseng SCG. Rose Bengal staining and cytologic changes associated with meibomian gland dysfunction. Am J Ophthalmol 1997;124: 736-50.

30.Tabbara KF, Okumoto M. Ocular ferning test. A qualitative test for mucus deficiency. Ophthalmology 1982;89:712-14.

31.Coyle PK, Sibony PA. Viralantibodiesin normal tears. Invest Ophthalmol Vis Sci 1988;29:10.

32.FullardRJ, SnyderC.Proteinlevelsinnon-stimu- lated and stimulated tears of normal human subjects. Invest Ophthalmol Vis Sci 1990;32:8.

33.Pflugfelder SC, Whitcher JP, Daniels TE. Sjögren’s syndrome In: Pepose J, Holland G, Whilhelmus K (Eds). Ocular infection and immunity. St. Louis, Mosby, 1997.

34.Pflugfelder SC, et al. Chronic Epstein-Barr viral infection and immunologic dysfunction in patients with aqueous tear deficiency. Ophthalmology 1990;97:313-23.

Fig. 26.1. Lacrimal system

is paler than its surrounding, serving as a guide in case of finding a stenosed punctum.

The upper punctum is slightly medial relative to the lower but when the eyelids are closed they appose each other. The medial ends of the lower lid retractors also help stabilize the puncta and prevent punctal eversion on blinking. The patency of the puncta is maintained by the surrounding dense fibrous tissue continuous with the adjacent tarsal plate.

Canaliculi: The canaliculi are hollow tubes of 0.5 mm diameter connecting the puncta to the lacrimal sac. Each canaliculus has a vertical part, which is 2 mm in length and a horizontal part of 8-10 mm, which follows the eyelid margin converging towards the medial canthus. The canaliculi are enveloped by the orbicularis muscle fibers and elastic tissue, except on the posterior walls, which are covered by conjunctiva through which the probe can be easily seen. The upper is slightly shorter than the lower. There is a dilatation at the junction of these two parts, which is the ampulla. The canaliculi pierce the periorbita of the lacrimal sac separately, uniting at an angle of 25o to form a short common canaliculus

Evaluation of Epiphora 413

(0-5 mm long). It then enters a small diverticulum of the sac, the lacrimal sinus of Maier at a point on the posterolateral surface of the sac about 2.5 mm from the apex of the sac. The common canaliculus is directed anteriorly forming an acute angle of about 45o with the sac before entering it. This acute entry into the lacrimal sac creates a potential mucosal flap or valve across the opening, the valve of Rosenmuller.2,3

The canaliculi are lined by stratified squamous epithelium supported with elastic tissue that can be dilated to three times the normal diameter.2

Lacrimal sac: The lacrimal sac lies in the lacrimal fossa formed by the lacrimal bone and the frontal process of the maxilla in the anterior part of the medial wall of the orbit which is continuous below with the nasolacrimal duct. Vertical suture line between the frontal process of the maxilla and the lacrimal bone is slightly medial to the middle of the floor of the fossa. This is of surgical importance because in dacryocystorhinostomy operation, the first bony opening is made through this line.

The lacrimal sac is 12-15 mm tall, 4-6 mm anteroposteriorly and 2-3 mm wide. The sac above the junction of the common canalicular duct is known as fundus. An imaginary line drawn from the medial canthus to the first upper molar tooth that slopes downward and backward at 15-25° indicates the long axis of the sac.

A portion of the periorbita, which splits at the posterior lacrimal crest, encloses the lacrimal sac and then joins at the anterior lacrimal crest forming the anterior and the posterior lacrimal fascia, respectively. Anterior ethmoidal air cells and vessels are medial to the upper part of the sac, the cribriform plate and the frontal sinus floor lie superior to the sac. Between the posterior surface of the sac and the posterior lacrimal fascia there is a vascular plexus; injury to the plexus cause troublesome bleeding. Anteriorly, the upper

414Diagnostic Procedures in Ophthalmology

part of the sac is in close contact with the medial palpebral ligament so much that the ligament may have to be divided near its attachment to the anterior lacrimal crest for complete mobilization of the sac. The angular vein crosses the ligament subcutaneously 8 mm from the medial canthus; however, the position of the vein is not always constant. Incision for removal of the sac should not be more that 2-3 mm medial to the medial canthus.

Nerve supply of the lacrimal sac is by the infratrochlear branch of the nasociliary nerve.

Blood supply of the lacrimal sac is via the dorsalis nasi and medial superior palpebral, both being branches of the ophthalmic artery, angular branch of the facial artery, branch of the external maxillary artery and the infraorbital branch of the internal maxillary artery. Venous drainage is through the rich venous plexus surrounding the sac into the angular vein.

Nasolacrimal duct: The nasolacrimal duct is a continuation of the lacrimal sac. There is only a slight constriction at the junction of the nasolacrimal duct and the sac. The long axis is along the line joining the medial canthus to the first molar. It can be identified from outside by the more numerous and prominent vein surrounding the duct than the sac and from inside by the focal narrowing (valve of Krause) at the junction. The duct also has a thicker wall which becomes apparent on incision.

The nasolacrimal duct can be divided into two parts, an interosseous part (12 mm approximately) and an intermeatal part (5 mm approximately). It lies embedded in a bony canal formed medially by the maxillary bone and laterally by the lacrimal bone above and the inferior conchea below. The nasolacrimal duct opens on the lateral wall of the nasal cavity about 10 mm posterior to the anterior end of the inferior conchea and 30 mm from the external nares. The duct opening has a mucosal fold, the valve of

Hasner, which prevents air from entering the lacrimal sac on sudden blowing the nose. The duct opening varies in size, shape and also the site of opening.

The duct is surrounded by a network of venous plexus. The plexus of vessels when engorged is sufficient to obstruct the duct.

Nerve supply to the duct is by the infratrochlear and the anterior superior alveolar nerves.

Blood supply of the nasolacrimal duct is from the palpebral branches of the ophthalmic, angular and infraorbital arteries and nasal branch of the sphenopalatine. Venous drainage is via the angular and the infraorbital vessels above and below into the nasal veins. Lymphatics of the nasolacrimal duct pass onto the submandibular and deep cervical nodes.

Orbicularis Oculi

Orbicularis oculi is the muscle that acts as the protector of the eyes through its blinking action. It has got two main parts—the orbital and the palpebral part. Our main concern here is the latter. The palpebral part is again divided into pretarsal—that part of orbicularis lying over the tarsus and the preseptal part over the orbital septum. The insertions of the orbicularis at the medial canthus around the lacrimal sac are called heads.

The preseptal part has its superficial head inserted into the medial canthal tendon and the deep head into the fascia on the dome of the lacrimal sac and into the upper part of the posterior lacrimal crest.

The pretarsal part has its circumferential fibers oriented over the superior and inferior tarsal plate. Laterally, it originates from the horizontal raphe and also from the lateral orbital tubercle. Medially, it is inserted into the anterior and posterior lacrimal crest by its two heads—the superficial and the deep head.

Two other muscle strips, the marginal preciliary and the retrociliary (muscle of Riolan) exist that are part of the pretarsal part of the orbicularis oculi.

Nerve supply to the orbicularis oculi muscle is by the facial nerve.

Tear Secretion and Elimination4-6

Tear secretions are mainly by the two sets of glands—lacrimal and the accessory glands of Wolfring and Krause. The accessory glands are the basal secretory that give a constant supply of tears as they lack any known innervations. The lacrimal gland is the reflex secretor. Autonomic stimulation; emotional stimulation; conjunctival, corneal or uveal irritation or irritative foci in the sinus, mouth, ear, or teeth lead to reflex tearing. It can accompany yawning, laughing, sneezing and coughing.

Tears are distributed along the conjunctival fornices, precorneal tear film and the marginal tear strips. Approximately 25% of the secreted tears are lost by evaporation. Rest are drained through the lacrimal drainage system via the punctum, the canaliculi, the sac, the nasolacrimal duct and ultimately into the inferior meatus of the nose. About 60% of the tears are drained via the lower punctum but in case of abnormalities the upper punctum can function efficiently without overflow.6

The blinking action of the eyelids helps in driving the tears forward into the drainage system. Blinking displaces the upper as well as the lower lid medially due to the firm attachment of the orbicularis to the medial canthal tendon. Moreover, with each blink the upper and lower lid approximates at the lateral canthal area and then proceeds towards the medial canthus displacing the tear film towards the puncta.

Even in the absence of blinking, low flow of tears occurs through the puncta due to the Krehbiel phenomenon, capillary action and the

Evaluation of Epiphora 415

normal downhill slope of the eyelids but along with a passive reflux into the lacrimal lake.

With the start of the blink the tears are propelled towards the puncta. As the process continues the open puncta move towards each other and occlude. Due to the orientation of the superficial and the deep heads of the orbicularis around the canaliculi and their firm attachment to the bone, the eyelid is pulled medially on contraction, the canaliculi are shortened squeezing the tear already in the ampulla and the canaliculi into the sac. The attachment of the deep head of the preseptal part of the orbicularis into the fascia on the dome of the lacrimal sac pulls the sac laterally on contraction enabling the sac filling (negative pressure). The valve of Rosenmuller reduces backflow, once the tears are in the sac.

On opening the eyes, the muscle around the canaliculi relaxes leading to the flow of tears into canaliculi again due to the reduced intracanalicular pressure. Tears can also gravitate down the nasolacrimal duct passively. But active drainage into the nose is by the complex action of the Horner muscle.

Evaluation of Epiphora

Tearing can broadly be grouped under two main headings:

1.Lacrimation (Hypersecretion of tears)

2.Epiphora (Impairment of drainage)

It is essential to differentiate between two in

planning the management.

•Epiphora is a condition where there is excessive tearing due to reduced tear outflow, i.e. defective tear drainage.

Obstruction at any point along the lacrimal drainage pathway, from the punctum to the nose can cause epiphora. This can lead to epiphora varying in severity from intermittent epiphora with a partial block to tears

416 Diagnostic Procedures in Ophthalmology

overflowing to the cheek. It can be unilateral or bilateral. It is worse in winter months and windy weather. Vision can be affected more on down gaze due to elevated tear meniscus or tear splattered glasses. Chronic epiphora can cause red, sore lower-lid skin, with secondary anterior lamella (vertical) shortening (mild cicatrical ectropion). Excessive wiping away of tears can cause or exacerbate a medial ectropion.

•Functional epiphora is the term that is used when there is epiphora with patent syringing, in the absence of any causes of hypersecretion. This may be due to a narrowing or stenosis of the nasolacrimal duct, which increases the resistance to the tear outflow but does not cause a complete anatomical obstruction. The term lacrimal pump dysfunction is used for epiphora due to reduced tear drainage of orbicularis causes. Common causes of functional epiphora are punctal stenosis, facial palsy with paralytic ectropion, single functional canaliculus and common canalicular stenosis.

•Pseudoepiphora refers to the reflex hypersecretion of aqueous tears from the main lacrimal gland due to altered production by the glands of Krause and Wolfring.7

Evaluating a case of epiphora needs a systematic approach, so that the causes of hypersecretion can also be ruled out.

History

A meticulous history taking is vital to the evaluation. Patient‘s symptoms, past ophthalmic, nasal and medical history should be elicited. A history of allergic diathesis and use of drugs should be obtained.

In case of congenital tearing, parents may complain of constant tearing with minimal or no mucopurulent discharge suggesting upper

system block (punctal or canalicular dysgenesis). Constant tearing with frequent mucopurulent discharge and matting of the lashes suggest nasolacrimal duct block. Intermittent tearing with mucopurulence may suggest intermittent obstruction of the nasolacrimal duct (impaction of a swollen inferior nasal turbinate associated with an upper respiratory tract infection).

Examination

The lacrimal examination can be divided under three heading:

1.Periorbital, lid and lacrimal system assessment

General examination of the face, periorbital and medial canthal areas and eyelids is essential. It includes:

•Slit-lamp examination of the puncta, external eye and tear meniscus,

•Syringing,

•Diagnostic probing and

•Fluorescein dye test.

2.Examination of the nasal cavity

3.Radiological examination

4.Newer modalities

Periorbital, Lid and Lacrimal System Assessment8

General examination of the face and periorbital region: Examination of these parts with relevance to the symptoms help in establishing a diagnosis. Eyelid malposition, facial and periorbital asymmetry should be looked for.

Lacrimal sac swelling: A lump over the medial canthal area below the medial palpebral ligament strongly indicates to a lacrimal sac swelling (Fig. 26.2).

Evidence of inflammation: Fistula (Fig. 26.3) and inflammation over the sac area need to be further evaluated.

Fig. 26.2: Swelling above the area of the lacrimal sac in a child

Fig. 26.3: Acute dacryocystitis with fistula

Shortening of anterior lamella: Vertical eyelid tightness should be checked by asking the patient to look up at the ceiling. If there is short anterior lamella, the ectropion will be exacerbated.

Assessment of puncta: All the four puncta should be looked for the presence of any stenosis or membrane blocking them. They should face towards the lacrimal lake. The relative position of the upper and the lower puncta to each other and to the caruncle should also be assessed.

Eyelid laxity: The eyelid can in itself be a cause of epiphora. Involutional ectropion often progresses from punctal eversion to involve the medial third, then the medial half of the lower eyelid and eventually the entire lid. Examination

Evaluation of Epiphora 417

of the lid with utmost care is needed to diagnose the condition.

Horizontal laxity of the eyelid can be estimated by Pinch test and snap back test:

•Pinch test: Using the thumb and the index finger, the lid is pulled firmly away from the globe, the distance between the lid and the eye is measured and the laxity is documented

•Snap back test: The speed with which the lower lid settles back against the globe after being pulled down and released is to be observed, as well as whether there is a short gap between the lid and globe once settled and before the first blink.

•Medial canthal tendon laxity: It is always to be assessed while evaluating a case of epiphora. It is graded with the lateral distraction test and by noting the position of the lower punctum in relation to the upper. These tests depend on the fact that the lower puncta normally lies at the plica at rest and also when pulled laterally.

The patient is made to sit in front of the examiner at arm length distance with their eyes at the same level. The patient is asked to look at the bridge of the examiner’s nose and without inducing accommodative convergence by moving too close, the lower punctum position is noted relative to the upper.

-1 Punctal medialization 0 Normal

+1 Midway between the plica and the medial limbus

+2 In line with the medial limbus

+3 - +6 Beyond the medial limbus

418Diagnostic Procedures in Ophthalmology

•Lateral distraction test: After noting the resting position of the lower punctum, the lower lid is pulled laterally and the position of the punctum is noted again. The test is graded as:

0 No distraction at all

+1 Punctum reaches midpoint of plica and medial limbus

+2 Punctum reaches medial limbus

+3 Punctum reaches midpoint of medial limbus and pupil line

+4 Punctum reaches pupil line

+5 Punctum reaches midpoint of pupil line and limbus line

+6 Punctum reaches lateral limbus

Slit-lamp Examination

The slit-lamp examination is an essential part of evaluation.

•Punctum should be evaluated for patency, size, position and discharge.

•Mild degrees of ectropion (Fig. 26.4) and entropion (Fig. 26.5) that are not apparent to gross external examination may be revealed on the slit-lamp biomicroscopy. Small lesions of eyelid margins like papillomas, molluscum contagiosum, chalazia, nevi and carcinoma are best detected with the slit-lamp.

•Pressure over the lacrimal sac may cause discharge from the punctum, suggesting nasolacrimal duct obstruction.

•Presence of inflammation on the area overlying the canaliculus and discharge from the punctum on pressure over the area may suggest canaliculitis (Fig. 26.6).

•Examination for the signs of blepharitis (Fig. 26.7) as well as dry eye syndrome which lead to hypersecretion of tears should be looked for. Conjunctival lesions particularly pinguecula and pterygium may induce tearing. The forniceal and palpebral conjunctiva should be inspected for follicles

Fig. 26.4: Involutional ectropion

Fig. 26.5: Congenital entropion

and papillae of reactive inflammatory disorders and allergic conjunctivitis.

•Cornea should be examined for any irregularities, features of dry eye syndrome or epithelial dystrophies. These examinations help to rule out causes of hyperlacrimation.

•The vertical height of the tear meniscus is to be measured prior to instillation of any eyedrops. Staining the tear film with a small amount of fluorescein aids in assessing the volume of the tear lake.

420Diagnostic Procedures in Ophthalmology

secretion by the glands of Krause and Wolfring.9,10 Wetting of less than 10 mm after 5 minutes indicates deficiency of basic tear production. A tearing patient with patent lacrimal drainage system with deficient basic tear production indicates towards reflex hypersecretion.

Schirmer II test measures the reflex tearing from the main lacrimal gland after eliminating the local causes of irritation. After anesthetizing the conjunctival sac, the trigeminal nerve is stimulated either with a cotton-tipped applicator applied to the nasal mucosa or with ammonium chloride on a cotton pledget held at the external nares. The amount of excess wetting in addition to that of the basic secretion test is the reflex secretion.

Fig. 26.9: Instruments used for syringing and probing

Syringing

Syringing the canalicular system provides information regarding the patency status. One to two drops of topical anesthesia (proparacaine or tetracaine) is instilled into the conjunctival sac. The punctum is dilated gently by advancing the Nettleship dilator (Figs 26.9 and 26.10), first

vertically for about 2 mm and then horizontally with a twisting movement. Simultaneously, lateral traction is applied to the eyelid. With the eyelid stretched, the dilator is withdrawn and the lacrimal cannula attached with syringe filled with normal saline is advanced horizontally through the punctum and the canaliculus (Fig. 26.10). No resistance should be felt in its entire path. Irrigation is then done and the patient is asked to respond if fluid passes into the oropharynx or nose.

If there is resistance to irrigation, obstruction is present. Regurgitation of fluid from the same punctum indicates that there is a canalicular block. Regurgitation of fluid from the upper punctum indicates blockage at the level of common canalicular duct, lacrimal sac or nasolacrimal duct. Immediate regurgitation of clear fluid usually suggests a common canalicular obstruction. Relatively delayed regurgitation of fluid mixed with mucus or pus usually indicates NLD blockage.

Diagnostic Probing

Probing the canaliculi provides information regarding the site of obstruction, which is necessary for decision-making. It is performed only after obstruction is demonstrated by other tests. After topical anesthesia of the conjunctival sac, the canaliculi are also irrigated with anesthetics. A probe of appropriate size is inserted into the punctum after dilatation and advanced till it meets obstruction. First it is passed vertically through the punctum, turned medially and advanced until it encounters the lacrimal bone (Fig. 26.11A).

Through out the procedure the lid should be firmly pulled laterally so that there is no kinking of the canaliculi. It is then withdrawn a few millimeters and rotated inferiorly and slightly posterolaterally until the proximal part of the nasolacrimal duct is felt. The probe is then

Evaluation of Epiphora 421

passed until it strikes the floor of the nose in the inferior meatus (Fig. 26.11B). If in between any obstruction is felt, the site of obstruction is noted by grasping the probe with a forceps at its entrance before withdrawing.

Figs 26.11A and B: Dilatation of punctum and probing

Obstruction can be felt as a “soft stop” in case of a stenosis of the canaliculus or as a “hard stop” astheprobehitstheboneatthemedialwallofthe lacrimal sac. Obstruction at less than 8 mm indicates a canalicular block, 8-10 mm indicates a common canalicular obstruction and distal to that if the probe passes more than 10 mm.

While probing a child, a few considerations should be noted. Probing is usually recommended through the upper canaliculi as the lower canaliculus carries more tear flow than the upper and it is wise to avoid the possibility of injury to it. Up to 1 year of age, the distance from the punctum to the nasolacrimal duct is approximately 12 mm, whereas, to the floor of the nose, it is approximately 20 mm.11

422Diagnostic Procedures in Ophthalmology

Fluorescein Dye Test

Dye disappearance test or fluorescein dye retention test: This is a semiquantitative test of delayed or obstructed tear outflow. It is of particular importance for the evaluation of congenital dacryostenosis in infants and toddlers where lacrimal irrigation is impossible without anesthesia and deep sedation. One drop of 2% fluorescein is instilled into the unanesthetized conjunctival sac of both the eyes. The volume of the tear lake is then noted preferably under the cobalt blue light. The patient is instructed not to wipe the eyes. The tear lakes are examined 5 minutes later, and the relative volume is determined. Persistence of significant dye and especially asymmetric clearance of the dye from the tear meniscus over a 5 minutes period indicates a relative obstruction of the side retaining the dye.12,13

Jones tests: 14,15 The Jones tests are dye tests for functional epiphora where the lacrimal drainage system observed to be patent on syringing. There are two types of Jones tests (Figs 26.12A and B).

•Jones tests I: It investigates the lacrimal outflow under normal physiological conditions. Fluorescein (2%) is instilled into the conjunctival sac and presence of the dye at the inferior meatus is noted at 2 minutes and 5 minutes with the help of a cotton tip applicator. Rate of false negative is very high with this test.

•Jones tests II: It is a nonphysiological test that determines the presence or absence of fluorescein in the irrigating saline fluid retrieved from the nose. Flushing of the residual dye (of the unsuccessful Jones test I) from the conjunctival sac is done and after that topical anesthesia is instilled into the conjunctival sac. Patient is seated with head tilted forward and a transcanalicular irrigation with saline is done. Patient is then asked to blow or spit

Figs 26.12A and B: Jones test I and II

the fluid onto a paper tissue and fluorescein dye is looked for.

A positive test is with the presence of the dye on the tissue paper suggesting that the dye had reached the lacrimal sac but in the presence of a narrowed nasolacrimal duct or a nonfunctioning lacrimal pump requiring the syringing pressure to force it down.

The test is said to be negative when the tissue is clear of any dye indicating that it did not get into the lacrimal sac with the Jones I test as in eyelid malposition, lacrimal pump failure, punctal or canalicular stenosis.

A positive Jones test II confirms anatomical patency with a high-pressure wash out of fluorescein.

Modifications of Tests

Taste test: One drop of saccharin is instilled into the conjunctival sac and one gets the taste of

it after several minutes in case of a patent lacrimal drainage system.

Endonasal dye test: This is done as the Jones test I and presence of the dye is seen through an endoscope inserted into the nares.

Oropharynx dye appearance test: Fluorescein 2% is instilled into the conjunctival sac of one side at a time and the oropharynx is checked periodically for the appearance of the dye. This test is of particular importance in infants where sedation or anesthesia is otherwise needed.

Examination of Nasal Cavity

The key to success of a dacryocystorhinostomy surgery lies in the intact anatomy of the nasal cavity. Moreover, pathology of the structures around the opening of the nasolacrimal duct itself may be the cause of epiphora. Examination of the nasal cavity can be done either with a nasal speculum or more completely with a rigid nasal endoscope. Treatment of the existing pathology is necessary before contemplating surgical intervention.

Ancillary Radiological Investigations

Radiological tests help in confirming the site of obstruction or stenosis in case of blocked syringing, confirm a functional cause of epiphora and delineate the anatomical as well as the pathological process pertaining to the problem.

Dacryocystography

Dacryocystography (Figs 26.13 and 26.14) is of importance in case of blocked syringing to locate the site of obstruction. Moreover, it gives additional information regarding any fistula or intrasac pathology.

After instillation of local anesthesia, a fine catheter is introduced into the canaliculus (preferably the superior one) and 0.5-2 ml of water soluble iodinated contrast medium is injected

Evaluation of Epiphora 423

Fig. 26.13: Dacryocystography showing passage of contrast into the nasal cavity

Fig. 26.14: Dacryocystography showing pooling of contrast in the lacrimal sac (NLD obstruction)

continuously during either conventional tomography or CT acquisition. CT dacryocystography is considered superior to conventional one as it provides useful anatomical information about the orbital wall, sinus as well as allowing evaluation of the nasolacrimal duct.

MRI dacryocystography provides the same information as the conventional studies, without the use of catheterization and contrast medium. Both the sides are preferably done simultaneously

424Diagnostic Procedures in Ophthalmology

in case of a functional epiphora. Enhancement of the film is done with digital subtraction (Fig. 26.15).16,17

Fig. 26.15: Dacryocystography after digital subtraction

Dacryoscintigraphy18-20

Functional epiphora becomes difficult to differentiate from partial block of the lacrimal drainage system. Dacryoscintigraphy assesses the lacrimal drainage system under physiological condition.Technetium-99, a gamma ray-emitting radionuclide in saline or technetium sulfur colloid are instilled into the conjunctival sac and imaged with a gamma camera at fixed interval. Delay in the passage of the dye may occur at any site as in the region of the conjunctival sac or the canaliculi, which may be due to lid or canalicular diseases. Apart from being a noninvasive technique, radiation exposure to the lens is minimal compared to that of dacryocystography. The disadvantage of dacryoscintigraphy is that it lacks in showing finer anatomical detail.

Computer Tomography (CT)21

The role of CT scan comes when anatomical or pathological abnormalities are suspected as the

underlying cause of epiphora which may be due to craniofacial injury, congenital deformities or lacrimal sac neoplasia. The paranasal sinuses, especially the maxillary sinuses are imaged for any abnormalities that might be affecting the nasolacrimal duct. Preoperative assessment of the cribriform plate is noted for any abnormal position to avoid a possible cerebrospinal leak at the time of surgery.

Newer Modalities

Chemiluminescence test22: Cyalume, a chemiluminescent material is injected with a sialography catheter to demonstrate the patency of outflow passages.

Dacryoscopy: Dacryoscope, a mini rigid endoscope allows the direct visualization of the interior and the lining of the lacrimal passages.23,24

Standarized echography: Gross anatomical structural defects can be evaluated with the standardized echography.25

Thermography: Thermographic evaluation of the lacrimal passage used in conjunction with routine lacrimal irrigation to visualize the tear ducts in normal subjects and in a patient with obstructive epiphora has been described.26

References

1.Jane Olver J. Colour Atlas of Lacrimal Surgery. London, ButterworthHeinemann 2002;11-26.

2.Bron AJ, Tripathi RC, Tripathi B. Wolff’s Anatomy of the eye and orbit. 8th edn. Edinburgh, Chapman & Hall Medical Publication 1997;72-84.

3.Tucker NA, Tucker SM, Linberg JV. The anatomy of the common canaliculus. Arch Ophthalmol 1996;114:1231-34.

4.William MH Jr. (Ed). Adler’s Physiology of the Eye: Clinical Application 9th edn. Harcourt Brace Asia 1992.

5.Doane MG. Blinking and the mechanics of the lacrimal drainage system. Ophthalmology 1981; 88:844-50.

6.Becker BB. Tricompartmental model of the lacrimal pump mechanism. Ophthalmology 1992; 99:1139-45.

7.Basic and clinical science course, American Academy Ophthalmology, 2005; Orbit, eyelids and the lacrimal system. Chapter 14-Evaluation and management of the tearing patient, 272.

8.Conway ST. Evaluation and management of “functional” nasolacrimal blockage: results of a survey of the American Society of Ophthalmic Plastic and Reconstructive surgery. Ophth Plastic Reconstr Surg 1994;10:185-87.

9.Krupin T, Cross D A, Becker B. Decreased basal tear production associated with general anesthesia. Arch Ophthalmol 1977;95:107.

10.Lamberts DW, Foster CS, Perry HD. Schirmer test after topical anesthesia and the tear meniscus height in normal eye. Arch Ophthalmol 1979;97:1082.

11.Nesi FA, Lisman RD, Levine MR. Smith’s Ophthalmic plastic and reconstructive surgery. 2nd edn. St Louis, Mosby 649-60.

12.FlackA.Thefluoresceinappearancetestforlacrimal obstruction. Ann Ophthalmol 1979; 11:237.

13.MacEwen CJ, Young JDH. The effect of fluorescein disappearance test (FDT): an evaluation of itsusesininfants.JPaedOphthalStrab1991;28:305.

14.Zappia RJ, Milder B. Lacrimal drainage function.I. The Jones fluorescein test. Am J Ophthalmol 1972; 74:154-59.

15.Zappia RJ, Milder B. Lacrimal drainage function.I. The fluorescein dye disappearance test. Am J Ophthalmol 1972;74:160-62.

Evaluation of Epiphora 425

16.Galloway JE, Kavic TA, Raflo GT. Digital substraction macrodacryocystography. Ophthalmology 1984;91:956-62.

17.Lloyd GAG, Welham RAN. Substraction macrodacryocystography. Br J Radiol 1972;47: 379-82.

18.Rossomondo RM, Carlton WH, Trueblood JH. A new method of evaluating lacrimal drainage.

Arch Ophthalmol 1972;88:523.

19.Hurwitz JJ, Maisey MN, Welham RAN. Quantitative lacrimal scintillography. Br J Ophthalmol 1975;59:308-12.

20.Jedrzynski MS, Bullock JD. Radionuclide dacryocystography. Orbit 1998;17:1-25.

21.Kallman JE, Foster JA, Wulc AE, et al. Computer tomography in lacrimal outflow obstruction. Ophthalmology 1997;104:676-82.

22.Raflo GT. Assessment of efficacy of chemiluminance evaluation of lacrimal drainage system.

Ophthalmic Surgery 1982;13:36.

23.Coehn SW, Prescott R, Sherman M. Dacryoscopy. Ophthalmic Surgery 1979;10:57.

24.Tsugihisa Sasaki, Yuuko Nagata, Kazuhisa Sugiyama. Nasolacrimal duct obstruction classified by dacryoendoscopy and treated with inferior meatal dacryorhinostomy. Part I: Positional diagnosis of primary nasolacrimal duct obstruction with dacryoendoscope. Am J Ophthalmol 2005;140:1065-69.

25.Dutton JJ. Standardised echography in the diagnosis of lacrimal drainage dysfunction. Arch Ophthalmol 1989;197:1010.

26.Raflo GT, Chant P, Hurwitz JJ. Thermographic evaluation of lacrimal drainage system.

Ophthalmic Surgery 1982;13:119.

Fig. 27.3: A child with acute onset proptosis of the right eye suggestive of an orbital malignancy

not uncommon in developing countries. Endocrine disturbances, such as thyroid dysfunction, could have some of their earliest manifestations in the orbit and adnexa.

In a case of proptosis, as in any other clinical situation, the diagnostic work-up begins with a careful history and clinical examination. The degree of proptosis is quantified by performing an exophthalmometry. The most commonly used instrument is the Hertel’s exophthalmometer (Fig. 27.4), in which the position of the anterior corneal surface is recorded, taking the lateral orbital rim as a reference point. An absolute reading greater than 21 mm or a relative difference of more than 2 mm between the two eyes is used as a cutoff value for diagnosing proptosis. Some of the

Fig. 27.4: Hertel’s exophthalmometer

Diagnostic Techniques in Proptosis 427

important clinical parameters to be taken into consideration are the laterality, direction of globe displacement, characteristics of the mass if palpable, visual status and posterior segment evaluation. A vast array of diagnostic techniques have evolved over the years to confirm the presumptive clinical diagnosis. This chapter describes techniques which complement the process of diagnosis in a case of proptosis and are crucial for appropriate management.

Diagnostic Techniques

A large number of diagnostic techniques are available for evaluation of a case of proptosis. However, as a general principle, one should follow a graded approach in employing these techniques, starting with the less invasive ones and going on to the more invasive ones, only if indicated. One should also be able to distinguish as to which group of investigations would be relevant in a particular case. The noninvasive techniques include imaging studies, which are the cornerstone in reaching a diagnosis in a case of proptosis. Invasive techniques are aimed mainly on efforts to reach a tissue diagnosis, which entails harvesting of tissue and subjecting it to routine and specialized histopathological tests.

Imaging Techniques

Standard Roentgenography (Plain X-ray)

Standard X-rays of the orbit were a useful imaging technique for initial screening before the advent of CT. They are of value in demonstrating bony changes and particularly fractures and foreign bodies in the orbit. Special optic foramen views can be obtained to visualize enlargement which can denote apical tumors. There are a variety of views of the orbit that can be requested, each

428Diagnostic Procedures in Ophthalmology

with its own specific benefits. These include the Caldwell view (general view), Water’s view (orbital view), Rhese view (optic foramen) and Lateral view/axial basal view (paranasal sinuses).

Important findings to look out for include orbital enlargement (trauma, benign tumor), orbital wall erosion (benign pathology), orbital wall destruction (malignant pathology), calcification (phlebolith, meningioma, lacrimal gland carcinoma, retinoblastoma), hyperostosis (meningioma, Paget’s disease, malignant osteoblastic secondary, fibrous dysplasia), enlargement of the optic foramen (optic nerve glioma, meningioma) and enlargement of the superior orbital fissure (aneurysm or tumor with posterior extension).

Ultrasonography (USG)

Ultrasonography is a rapid noninvasive tool for the evaluation of orbital lesions causing proptosis. As most USG machines are compact and portable, it can be performed in an office setting as well as peroperatively. It gives useful information about the characteristics of the lesion and can even clinch the diagnosis when done by an experienced observer. Despite being inferior to CT-scan and MRI in depicting the bony wall, orbital apex, adjacent sinuses and intracranial compartments, ultrasound is arguably a better imaging modality in the detection of subtle changes of the soft tissues within the orbit, and the differentiation of extraocular muscles and optic nerve lesions. The machine basically consists of a transducer at the tip of a probe which emits ultrasonic waves by the vibration of a piezo-electric crystal inside the probe. These waves are reflected, scattered and absorbed by the medium. The reflected waves are then processed in a computer to generate a single or multidimensional picture on a screen. Ophthalmic USG uses frequencies ranging

between 6 and 20 MHz (typically 10 MHz). The speed of sound varies with the medium, and in the orbit it is usually 1550 m/s. The lower frequencies provide better penetration but lower resolution and vice-versa. Ultrasound is, however, of limited value in assessing lesions of the posterior orbit; (sound waves at 8-10 MHz do not penetrate beyond the mid-orbit) or the sinuses or intracranial space.

Standardized A-scan is a time-amplitude display mode where we get one dimensional display of vertical (amplitude) spike and the horizontal axis which is modified to display the distance in millimeters. The A-scan gives us important information regarding the internal structure of a lesion. For example clear cysts and homogenous solid lesions (e.g. lymphoma) typically produce low amplitude internal spikes (reflectivity) whereas heterogeneous lesions (e.g. hemangioma and dermoids) produce higher amplitude echoes within the normal orbital pattern.

B-scan is a two dimensional intensity modulated display. It is seen as a funnel-shaped display on the screen, the mouth of the funnel being on the right, the probe position (transducer band) is on the right and the horizontal extent on the right gives the depth of penetration of sound beam. The vertical axis represents the segment of the eye being scanned. B-scan allows a real time evaluation of any lesion and successive cross sections are displayed on the monitor. The signal amplitude is displayed as dots whose brightness gives an idea of the strength of the returning echoes, which is referred to as the Gray scale. Orbital B-scan can be transocular where the beam crosses the globe, which is then seen in front behind which the orbital shadow is displayed, or par-ocular, which bypasses the globe and is used mainly for anterior orbital lesions. B-scan shows rather characteristic alterations of the normal orbital pattern in various lesions such as tumors, cysts and inflammation.

430 Diagnostic Procedures in Ophthalmology

Fig. 27.7: Ultrasound picture showing an orbital cyst with scolex suggestive of cysticercosis

Fig. 27.8: Ultrasound picture showing an orbital cyst with “double wall sign” typical of hydatid cyst

reveal information on the extent of arterial or venous flow in the substance of the lesion.

Apart from these, there are other methods of USG like C-scan which depicts orbital lesions in a coronal plane and D-scan which provides a three dimensional display.

Three-dimensional ultrasound (3D USG) imaging is a novel way of imaging ophthalmic pathologies in vivo, revealing valuable topographic information in ways more familiar and recognizable to the untrained eye, where surfaces can be perceived and their approximate relationships in three-dimensions can be presented (e.g. to determine the contour and size

A

B

Figs 27. 9A and B: Color Doppler examination in a case of orbital varices. A Before and B After Valsalva maneuver showing low blood flow velocity on dynamic evaluation

of tumors, to ascertain the shape and relative configurations of tissues and structures in the eye). Three-dimensional USG imaging allows volumetric and topographic reconstruction of the vitreous, retina, choroid, sclera, and orbital structures. Volumetric reconstruction is valuable in tumor growth assessment, while topographic mapping provides a more comprehensive quantitative description of the surface and marginal parameters responsible for volumetric changes.

432 Diagnostic Procedures in Ophthalmology

Fig. 27.11: CT-scan (axial view) showing a well delineated, fusiform, intraconal mass isodense to the optic nerve, suggestive of glioma

whether it is homogeneous or heterogeneous, solid or cystic, presence of calcification and the effect of contrast enhancement. Benign tumors such as cavernous hemangioma, neurilemoma, dermoids and gliomas (Fig. 27.11) usually have rounded well circumscribed borders. Malignant lesions on the other hand have diffuse, irregular boundaries. Important features of thyroid ophthalmopathy include swelling of muscles maximally in the mid-portion (Fig. 27.12) (relative sparing of the tendons), slight uveo-scleral thickening, apical crowding, increase in the diameter of the retrobulbar optic nerve sheath, increased density of orbital fat, and anterior

Fig. 27.12: CT-scan (axial view) showing significant enlargement of extraocular muscles with sparing of tendons in a case of thyroid exophthalmos

Fig. 27.13: CT-scan (coronal view) showing an infiltrative lesion in the lacrimal gland fossa with irregular internal structure suggestive of a malignant lacrimal gland tumor

displacement of the lacrimal gland. CT is a useful modality for the evaluation of lacrimal fossa masses, especially epithelial tumors (Fig. 27.13). CT can adequately depict osseous alterations and calcifications, and can differentiate a group of epithelial tumors from inflammatory and lymphoproliferative conditions. Features specific of orbital pseudotumor include a poorly defined intraor extraconal mass close to the surface margin of the globe. In the myositic type one may get enlargement of one or more muscles close to their insertion, with ill-defined margins. Other features of orbital pseudotumor are that it typically involves muscles and tendon insertions, there is increased density of retroorbital fat, thickening and enhancement of sclera near Tenon’s capsule and enlargement of the lacrimal gland. Lymphangioma may be diagnosed if there is a multi-lobulated pattern on CT-scan (Fig. 27.10) and a cystic internal structure in standardized ultrasound evaluation. Cavernous hemangiomas show as well circumscribed, solid, masses involving the intra or extraconal compartment. On CT-scan lymphoproliferative tumors typically show up as a localized or diffuse mass with moulding to the orbital structures.

Fig. 27.14: A patient undergoing an MRI-scan

Magnetic Resonance Imaging

Magnetic resonance imaging (MRI) is a noninvasive imaging technique which does not employ ionizing radiation and has no known adverse biological effects. The process involves a strong magnetic field which is applied to the body (Fig. 27.14). It excites protons in the body tissues and causes them to align in a particular orientation in relation to the magnetic field. When the magnetic field is switched off, the protons relax to their original alignment and re-emit the energy gained. The signal is recorded in terms of intensity and location. T1 weighting and T2 weighting refer to two methods of measuring the relaxation times of the excited protons after the magnetic field is switched off. The various body tissues have different relaxation times and a given tissue may be T1 or T2 weighted, implying that is best visualized on that particular type of image. Coronal, sagittal and axial images can be directly obtained. A surface coil is used for ophthalmic purposes to enhance spatial resolution. Four basic parameters can be adjusted to identify different tissues: proton density of tissue, bulk motion of protons (flow), spin lattice

Diagnostic Techniques in Proptosis 433

relaxation time (T1) and spin-spin relaxation time (T2).

Tissues with high proton (hydrogen nuclei) density (e.g. fat) emit a high signal as does low proton flow (coagulated blood). Low signal is produced by bone, sclera and sinus air and faster proton flow like in flowing blood. In T1 image (short TR and TE, i.e. relaxation time and echo time, respectively), the fat is bright and vitreous dark, and is reverse in T2 image (long TR and TE). In proton density image (long TR and short TE), the vitreous is intermediate density as seen in muscle, and the fat is seen brightly.

Paramagnetic substances like melanin and methemoglobin alter the signal character of the image causing relative brightness on T1 weighted image. Similarly, gadolinium, a paramagnetic substance is used as a contrast agent (coupled with diethylenetriaminepenta acetic acid or DTPA). Using this, false negative tests have been vastly removed and imaging of meningiomas, demyelination, metastasis, meningeal lesions, ventricular abnormalities and pituitary masses have been greatly enhanced. A few contraindications are there to the administration of contrast, the relative ones being severe hepatic or renal dysfunction and absolute ones include sicklecell anemia and hemolytic anemia. Mild allergic reactions may still occur.

Technical advances in MRI include the use of various surface coils, motion artifact and fat suppression techniques which greatly enhance visualization of orbital images. Contrastenhanced MRI (using IV gadolinium) is helpful in the evaluation of orbital lesions such as cavernous hemangiomas, high-flow vascular malformations (IV gadolinium enhancement brightens vascularized lesions so that they exhibit the same density as fat), nonthyroid related extraocular muscle enlargement, which includes myositis or metastases, or processes that potentially extend into the cavernous sinus.

434 Diagnostic Procedures in Ophthalmology

Fig. 27.15: MRI-scan of the orbit (axial view, T1 weighted) showing a hyperintense lesion at the posterior pole suggestive of choroidal melanoma

On MRI, melanin within melanomas typically gives such tumors a hyperintense signal on T1weighted scans (Fig. 27.15) and hypointense signal on T2-weighted scans (Fig. 27.16) relative to the vitreous. Non-contrast, fat-suppression studies help to determine the extension of ocular melanoma into the orbit and optic nerve. Subretinal hemorrhage may be differentiated from choroidal melanoma by MRI when visualization is poor and ultrasound inconclusive. While MRI is a more useful diagnostic modality in lymphoangiomas (better anatomical illustration

Fig. 27.16: MRI-scan of the orbit (sagittal view, T2 weighted) showing a hypointense lesion at the posterior pole suggestive of choroidal melanoma

Fig. 27.17: MRI-scan of the orbit (sagittal view, T1 weighted) showing orbital metastasis

of the cystic nature of the lesion and the hemorrhages in lymphangiomas), it is interesting to note that these lesions typically do not enhance with gadolinium. In thyroid ophthalmopathy one notices a high signal intensity in enlarged eye muscles on T2W1. In orbital pseudotumor the lesion is isodense to fat on T2W1.

MRI of the orbit is especially useful in optic nerve lesions or trauma, unusual orbital inflammation, orbital metastasis (Fig. 27.17) and tumors extending to the orbital apex or having suspected intracranial extension.

Salient contraindications to performing an MRI scan include the presence of ferrous metallic foreign bodies (even mascara which contains ferrous compounds cause artifacts), aneurysm clips, cardiac pacemaker and cochlear implants. In addition, claustrophobic and obese patients may pose problems. Other limitations of MRI are lack of bone visualization, higher cost and longer time of scan.

An interesting advancement in MRI is

Magnetic Resonance Angiography (MRA) in which special software is used to suppress normal soft tissue to enhance vascular structures (Fig. 27.18). This is analogous to bone window setting on CT-scan. Gadolinium enhancement is needed

436Diagnostic Procedures in Ophthalmology

aneurysmsandhemangiopericytoma.Maximum visualization can be obtained by the use of magnification to allow viewing of the smaller caliber vessels, and subtraction techniques to radiologically eliminate bone. With the advent of MRI and CT, particularly MRA, its role and utility are gradually fading out.

Blood Tests

The nature of the blood investigations performed will depend to a large degree upon the clinical findings of the patient. Given herein are some of the more commonly utilized blood investigations to assist in the evaluation of a patient with proptosis.

Total and Differential Blood Counts

This test is particularly useful in evaluating patients with leukemia and lymphomas.

Thyroid Function Tests

Thyroid function tests include tests of T3, T4 and TSH. These tests will be abnormal in a majority of patients with thyroid ophthalmopathy. However, if thyroid disease is strongly suspected and these tests are normal, additional endocrine studies can be considered. Further tests which can be done include the antithyroglobulin and antimicrosomal antibodies, which are abnormal in nearly 70% of patients with Graves disease.

Antineutrophil Cytoplasmic Antibody (cANCA) Serum Assay

Diagnosis of Wegener’s granulomatosis should be considered in patients with scelrokeratitis or coexisting sinus disease and orbital mass lesions. The antineutrophil cytoplasmic antibody (cANCA) serum assay is a very sensitive test for the presence of this rare disease.

Serum Angiotensin Converting Enzyme

The diagnosis of sarcoidosis may be assisted by testing for serum angiotensin converting enzyme (ACE). This multi-system granulomatous inflammatory condition may present with lacrimal gland enlargement.

ELISA for Cysticercosis

Elisa test is used for evaluating the presence of an orbital cyst, if cysticercosis is suspected. However, it needs to be corroborated with clinical and imaging findings due to a high percentage of both false positive and false negative results.

Biopsy Techniques

Although imaging techniques can help us in making a provisional diagnosis and are indicative in nature, a definitive diagnosis can only be made by obtaining a tissue specimen and subjecting it to routine and specialized histopathological techniques. Biopsy techniques which are commonly employed are described below.

Fine Needle Aspiration Cytology

Fine needle aspiration cytology (FNAC) is employed for rapid diagnosis of suspected malignant orbital lesions. It is minimally invasive in nature and can be performed in an office setting. Although strict asepsis is mandatory, a full fledged operative set up is not required. It is done with the help of a hand held gun with 22 to 25 gauge needle (Fig. 27.19). After localizing the mass by palpation (for anterior orbital lesions) or under ultrasound or CT guidance (for relatively posterior lesions), the needle is introduced into the mass and the material is aspirated by using negative pressure. The aspirate is then spread over a slide, air dried, fixed in 95% alcohol and

Fig. 27.19: Instrument used for performing fine needle aspiration (FNAC gun)

finally stained with hematoxylin and eosin. The slide needs to be examined by a trained cytologist for accurate interpretation. The accuracy has been reported to be more than 80%. The principal disadvantage of this technique is that scanty cellular material is obtained from a limited region of the mass which may be difficult to evaluate and interpret. Secondly it uses cytology technique rather than routine histopathology that fails to detect tissue or tumor architecture. The main use of FNAC is in cases of suspected lymphoma metastatic tumors or orbital recurrence of retinoblastoma or melanoma, which may require to be treated by chemotherapy or radiotherapy. It has also been used for diagnosing optic nerve sheath meningioma.

Fine needle capillary sampling (FNCS) is another similar technique in which instead of aspiration with a syringe, a 25-gauge needle is introduced in the mass after stabilizing it manually. Gentle to and fro movement is performed and the needle is withdrawn without any aspiration. The material is then processed like FNAC. Reported sensitivity of this technique is said to be in the range of 90-95%. The complications of these procedures include globe perforation, retrobulbar hemorrhage and rarely intracranial penetration. Transient visual loss, diplopia and ptosis have also been reported.

Diagnostic Techniques in Proptosis 437

Core Biopsy

A somewhat more invasive technique than FNAC is core biopsy that uses a trephine which is 2- 4 mm in diameter. It is passed with a gradual rotatory motion into the lesion after exposure under local infiltration, and an adequate specimen is obtained. The advantages are that it is a rapid, out-patient procedure with lesser morbidity and much better yield of tissue than FNAC, for a more accurate diagnosis. Its main limitation is that posterior lesions are difficult to access. An endoscopic biopsy can be performed for the posterior lesions but requires greater expertise to yield credible results.

Incisional Biopsy

Incisional biopsy is a surgical technique where partial removal of the tumor is done under local or general anesthesia. The purpose of this biopsy is to obtain adequate tissue for histopathological examination. Imaging studies should be done for accurate localization of the lesion before undertaking the biopsy procedure. These are useful in planning the surgical approach. Care should be taken to obtain tissue from the main mass itself, because biopsy from superficial or adjacent structures will give false results.

Excisional Biopsy

Imaging and supportive investigations certainly help in establishing a good differential diagnosis, but a definitive diagnosis is sometimes established only after complete removal of the mass and subjecting it to histopathology. This is achieved by performing an orbitotomy procedure through one of the surgical approaches to the orbit. The principles of localization and surgical planning are similar to the ones described above. This, along with incisional biopsy, is the gold standard for diagnosis and

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has the added advantage of being therapeutic in benign encysted lesions like dermoids, cavernous hemangioma, pleomorphic adenoma of lacrimal gland, neurilemoma and fibrous histiocytoma.

Pathology Techniques

This area is the most important part of any diagnostic process as it provides actual tissue diagnosis, which may have therapeutic and medico-legal importance. It is imperative to have proper communication with the pathologist preoperatively, to facilitate and plan the appropriate histopathologic technique for a given case.

Cytology

As already stated under the section on FNAC, cytology is a low cost technique for rapid diagnosis. The aspirate is spread over a slide and air dried followed by alcohol fixation and stained by Papanicolaou technique and H&E or May-Grunwald-Giemsa stain; mainly used for suspected malignant lesions. Cytology has its limitations as discussed earlier.

Gross Examination

Thegrossexcisedspecimenisinspectedforshape, size, consistency (firm/hard/cystic/nodular), and whether the capsule is intact or broken. Measurements are made in three dimensions. Then it is cut to see the internal architecture – color, areas of necrosis, calcification and inner structure (solid or cystic). For example, on gross examination, pleomorphic adenoma of the lacrimal gland displays an intact capsule, with firm, bosselated appearance, and on cut section it has whitish, firm solid areas with some interspersed friable areas. Cavernous hemangioma on the other hand has a reddish-bluish color

Fig. 27.20: Gross specimen of an orbital cavernous hemangioma

Fig. 27.23: Gross section of an orbital cavernous hemangioma (gross specimen)

and has a firm to soft spongy consistency (Fig. 27.20). On cut section, it has a typical honeycomb pattern of innumerable cystic spaces (Fig. 27.21), whichcanbeverywellappreciatedonH&Estain (Fig. 27.22). Parasitic cysts, such as hydatid cyst are seen as a thin walled translucent fluid-filled structure (Fig. 27.23). The gross specimen is sent to the pathologist in a labeled bag filled with 10% formalin solution in adequate quantity.

Routine Histopathology

The biopsy or excised specimen is further processed in the pathological laboratory by

Fig. 27.22: Histopathological picture (H & E) of cavernous hemangioma showing large blood-filled spaces

Fig. 27.23: Gross specimen of a hydatid cyst of the orbit

dehydrating in alcohol. Then it is embedded in paraffin and sectioned with a microtome knife. This is followed by removal of paraffin and staining with hematoxylin and eosin stain (Fig. 27.24). Hematoxylin is a basic dye that binds acidic structures like DNA and nuclei in cells while eosin is an acidic dye that stains basic structures like proteins. This gives clues about the nature of the lesion. For example, cells with prominent nuclei and scanty cytoplasm will stain blue as in lymphoma, retinoblastoma, inflammatory lesions and basal cell carcinoma. On the other hand, cells with abundant cytoplasm like epithelial cells and connective tissue as in squamous cell carcinoma and amyloidosis, will stain pink.

Diagnostic Techniques in Proptosis 439

Fig. 27.24: Histpathological picture (H & E) of pleomorphic adenoma of the lacrimal gland

Histochemistry

In situations where the routine histological process is difficult to interpret, various histochemical and immunohistochemical techniques provide assistance. For example, Oil red O or Sudan black are used to stain fat in cases of sebaceous gland carcinoma or xanthomatous tumors. Similarly, Alcian blue is used for mucinous substances and PAS (Periodic acid Schiff) for glycogen and some fungal hyphae. Fontana is used for staining melanin, esterase for cytoplasmic granules in leucocytes and Bodian for nerve fibers.

Immunohistochemistry

Immuno-histo-chemistry is a highly sensitive technique, which utilizes the principle of antigenantibody reaction to capture certain specific proteins in specific tissues, which can then point out to the correct diagnosis. This reaction is coupled by an enzyme, which then generates a color reaction when combined with certain chemicals called chromogens. Monoclonal antibodies are directed against an important group of cytoskeletal components called intermediate filaments. These are specific for

440Diagnostic Procedures in Ophthalmology

different tissues and can be diagnostic. For instance, cytokeratins are found in epithelial cells and carcinomas, vimentin in mesenchymal cells and sarcomas, desmin in striated and smooth muscle cells, GFAP in glial cells and neurofilaments in neurons. Other examples are LCA (Leucocyte common antigen) used to stain lymphoid lesions; HMB 45 is used in melanomas, especially in cases of amelanotic melanoma where pigmentation may not be seen. S100 is used for schwannomas and neurofibromas. Similarly, specific antibody-antigen reactions are used to differentiate B cell from T cell lymphomas.

Electron Microscopy

Scanning Electron Microscopy (SEM) and Transmission Electron Microscopy (TEM) are sometimes used in evaluating unusual lesions. TEMcanbevitalinthediagnosisofcertaintumors suchasleiomyoma,neurilemoma,neurofibroma and amelanotic melanoma and also in certain poorly differentiated tumors like alveolar rhabdomyosarcoma and alveolar soft part sarcoma. It is an expensive and time consuming process.Withtheadventoftheabovementioned immunohistochemical stains, it is rarely used. SEM can be used to see the three dimensional ultrastructureoflesionsandcanprovideelemental details of retained foreign bodies.

Additional Investigations

Once the initial cause of the proptosis has been determined, it is often necessary to undertake additional investigations to further determine the full extent of the pathology. This is particularly true in the cases where the cause of the proptosis is found to be a tumor. For example patients with hematological and lymphoproliferative tumors require the following additional investigations: X-ray chest, blood

counts, serum immunoglobulin electrophoresis, bone marrow aspiration and biopsy, bone scan, liver and spleen scan and abdominal and pelvic CT.

Conclusion

Diagnosis of a case of proptosis requires a systematic approach through a proper clinical evaluation coupled with appropriate investigative techniques. If used effectively, these techniques can guide the clinician in achieving an accurate diagnosis and optimal management in this rather challenging field.

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