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6 Extraocular Muscle Tests andCover Tests

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b). The test provides information on the eye’s

ability to move with ease from a convergence (base-out prism), demand to a divergence (base in prism), demand (net change of 15-prism diopters), and vice versa (Fig.6.6c, d). The goal is to see how well the system can cope with the realworld demands of viewing different distances, such as directing attention from a whiteboard to a book. The prism ipper is alternated between 12-prism base-out and 3-prism base-in, and the patient is asked to report when the xated target appears single and clear (in focus). One cycle indicates the ability to clear both the base-out and the base-in prism. The number of cycles in 1min is recorded. The normal range expected for both distance and near in adolescent and young adults is 12±3cycles per minute [4, 15].

6.5 Clinical Application andInterpretation

The techniques described in Sect. 6.3 may be applied to virtually any scenario in pediatric ophthalmology, neuro-ophthalmology, optometry, binocular vision, vision therapy, and orthoptic clinics.

Case 1

A 21-month-old girl presented to the eye clinic for eye misalignment. Her eyes had been observed to cross inward since at least 4months of life. She was a twin, born at 34weeks gestation, and had a gastrostomy tube to improve her nutrition. Her twin sibling did not have any strabismus. Her ophthalmic examination indicated a normal ability to x and follow a target of interest with each eye, normal pupils, normal anterior segment, and normal dilated fundus examination. Her cycloplegic refraction showed age-appropriate hypermetropia of +2.50in each eye. Her extraocular motility examination demonstrated bilateral underaction of the superior obliques and associated overaction of the inferior obliques. On

initial version testing, she had difculty fully abducting each eye due to crossxation. However, on duction testing, each eye abducted normally. Krimsky testing was used to estimate the heterotropia, as cover testing could not be reliably performed as she was quite fearful of the examiner, which is typical for her age. Krimsky testing showed an esotropia of 45

Δ by one examiner and an esotropia of 40 Δ by a second examiner. The toddler was

diagnosed with infantile esotropia and scheduled for bilateral inferior oblique myectomies and bilateral medial rectus recessions. After the surgery, her alignment was orthotropic by Krimsky testing, and her mother volunteered without prompt that her gross motor skills had improved. Her mother reported that the toddler’s walking was steadier and more condent the day following the surgery.

Case 2

A 3-year-old girl presented to the eye clinic as the family noted that her left eye had been turning outwards since age two. Her ophthalmic examination indicated 20/30 vision using Lea symbols in the right and left eye, 50s of stereopsis with Randot circles, near point of convergence at 6 cm when the left eye loses fusion and drifts out, normal pupils, normal anterior segment, and a normal dilated eye exam. Cycloplegic refraction showed ageappropriate hypermetropia of +2.00in each eye. Her extraocular motility demonstrated mild inferior oblique overaction of 1+ in both eyes. Ductions in each eye were normal. The cover test revealed intermittent exotropia of 30 Δ for distance vision and 25 Δ for near vision with moderate control. She was diagnosed with intermittent exotropia and was recommended to have strabismus surgery to maintain binocularity.

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A. Raghuram and B. Jastrzembski

She had a bilateral lateral rectus recession of 6.5 mm. Six months post-surgery, she had small recurrent intermittent exotropia measured by cover test as 14 Δ for distance vision and 18 Δ at near vision with good control. For a year following surgery, recurrent intermittent exotropia continued to be observed with poor control and illsustained near point of convergence. She was referred to have a visual function examination to see if eye exercises could improve her control of the deviation.

On examination of her oculomotor function on the cover test, she had a 12 Δ constant left exotropia for distance vision and 14 Δ intermittent exotropia at near vision. The near point of convergence receded at 19cm, with the left eye drifting out. Positive fusional ranges at the near break at 6 and recovery at 0, indicating poor convergence ranges. Near vergence facility revealed an inability to clear the 12 Δ convergence demand ipper. She was recommended to work on some gross convergence exercises with a Brock string or just with an interesting target to focus on. As she continued to follow up, a loose prism for convergence training for both near and distance was also added. About 18 months post-surgery, she continued to have residual intermittent exotropia for distance and near vision at about 14 Δ, but with improved control for both distance and near vision. Her near point of convergence improved to a 7cm break and 9cm recovery with an accommodative target. At a distance, the positive fusional convergence ranges were break at 14 Δ and recovery at 12 Δ. For divergence ranges, the break was at 8 Δ and recovery at 2 Δ. For near convergence, the ranges were 16 Δ for break and 14 Δ for recovery; divergence ranges were 18 Δ for break and 14 Δ for recovery. The vergence facility could be recorded and normalized to 15 cycles per minute for near vision and 11 cycles per minute for distance vision. Eight years after surgery, she continued to

have residual intermittent exotropia but with improved control for both distance and near vision. Parents were happy that a second surgery was not required. She continued to make good eye contact, and spontaneous drifting of the left eye out occurred only when she was fatigued.

6.6 Conclusion

Extraocular motility and cover tests are integral to comprehensive eye examinations and are especially useful in neuro-ophthalmologic, strabismic, and non-strabismic binocular vision/visual function contexts. The motility and alignment/ cover tests described in this chapter characterize strabismus for diagnosis and surgical planning. In addition, testing of the vergence system provides additional information about how the eyes move together for typical tasks outside of an eye lane. Vergence system information may help determine when strabismus surgery may be unnecessary or guide adjuvant convergence exercises after surgery, as in Case 2. With a bit of practice and minimal equipment, the extraocular motor and cover tests quickly provide an examiner with a host of practical information about the afferent and efferent systems.

Acknowledgments We thank Carissa Wu and Neerali Vyas for assistance with the photographs and gures.

Funding Aparna Raghuram: Boston Children Foundation Discovery Award; Benjamin Jastrzembski: none.

Disclosure None.

References

1. Molnár Z, Brown RE. Insights into the life and work of sir Charles Sherrington. Nat Rev Neurosci. 2010;11(6):429–36.

2. Aminoff MJ, Daroff RB, editors. Encyclopedia of the neurological sciences. 2nd ed. Waltham: Academic Press/Elsevier; 2014. p.4.

6 Extraocular Muscle Tests andCover Tests

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3. Rowe FJ. Clinical orthoptics. 3rd ed. Chichester: Wiley-Blackwell; 2012.

4. Scheiman M, Wick B.Clinical management of binocular vision: heterophoric, accommodative, and eye movement disorders. 3rd ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins; 2008. p.748.

5. Raghuram A, Cotter SA, Gowrisankaran S, et al. Postconcussion: receded near point of convergence is not diagnostic of convergence insufciency. Am J Ophthalmol. 2019;206:235–44.

6. Raghuram A, Gowrisankaran S, Swanson E, et al. Frequency of visual decits in children with developmental dyslexia. JAMA Ophthalmol. 2018;136(10):1089.

7. Scheiman M, Gallaway M, Frantz KA, et al. Nearpoint of convergence: test procedure, target selection, and normative data. Optom Vis Sci. 2003;80(3):214–25.

8. Convergence Insufciency Treatment Trial Study Group. Randomized clinical trial of treatments for symptomatic convergence insufciency in children. Arch Ophthalmol. 2008;126(10):1336.

9. Convergence Insufciency Treatment Trial Group. Manual of procedures. 2023. https://optometry.osu.

edu/CITT- manual- procedures.

10. Pediatric Eye Disease Investigator Group. Homebased therapy for symptomatic convergence insufciency in children: a randomized clinical trial. Optom Vis Sci. 2016;93(12):1457–65.

11. Morgan MW Jr. Analysis of clinical data. Optom Vis Sci. 1944;21(12):477–91.

12. Scheiman M, Wick B.Clinical management of binocular vision: heterophoric, accommodative, and eye movement disorders. 4th ed. Philadelphia: Lippincott Williams & Wilkins; 2014. p.722.

13. Wajuihian SO. Normative values for clinical measures used to classify accommodative and vergence anomalies in a sample of high school children in South Africa. J Opt. 2019;12(3):143–60.

14. Haines HF. Normal values of visual functions and their application in case analysis. The analysis of ndings and determination of normals: part IV.Optom Vis Sci. 1941;18(2):58–73.

15. Gall R, Wick B, Bedell H. Vergence facility: establishing clinical utility. Optom Vis Sci. 1998;75(10):731–42.

The Pupil andPupillary Reexes

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MeenakshiSwaminathan andGayathriJ.Panicker

7.1 Introduction

A systematic examination of the pupils begins with a thorough patient history. A difference in the size of the pupils (anisocoria) may have been noticed by a friend or a family member, especially in people with light-colored irises. Patients with anisocoria may complain of photophobia, difculty in focusing, and blurred vision when going from light to dark areas and vice versa. A systematic search of their medical histories and documenting conditions such as migraine and diabetes, if any, is also important [1]. Other points in recording patient history include noting a history of cataract surgery, uveitis, use of dilating or constricting eye drops, exposure to pesticides, use of opiates (which can constrict pupils), and anticholinergics in asthma medications (which can dilate pupils) [2, 3].

The following points must be specially noted

while examining the pupils [4].

1. Pupil size: Is it appropriate for the age of the patient? Pupil size can decrease with increasing age.

2. Equality of pupil size: Unequal pupil size is called anisocoria. It is also important to note if the difference is greater in light or dark.

M. Swaminathan (*) · G. J. Panicker Sri Ramachandra Institute of Higher Education and Research, Chennai, India e-mail: drgjp@sriramachandra.edu.in

3. Pupil response to light: Is there equal constriction in both eyes in size and velocity?

4. Pupil dilation: Is it equal in both eyes in size and velocity?

5. Response to light and a near target: Do the pupils respond, and is the response equal in both eyes?

6. Presence of afferent pupillary defects.

7.2 Pupil Size Measurement

This is done using a pupil gauge which may be a circular disc or linear scale with increments of

0.1 mm. A handheld pupil camera adds more

accuracy to the measurement but is not helpful for pupil measurement in the dark. Infrared video pupillometry overcomes this disadvantage and can capture pupil size in both light and dark conditions [5]. The velocity and latency of the pupillary response can be calculated with software linked to the video input.

7.2.1 Clinical Examination

andInterpretation ofAnisocoria

Anisocoria is dened as a difference in the pupillary diameter between the eyes of >0.4mm. The light source used to examine the diameter of the pupil can be normal room light (easy to see the

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M. Swaminathan and G. J. Panicker

difference in light-colored irises) or a ashlight shone from below, illuminating both pupils equally with the room lights on. This gives an idea of pupillary size in light. To estimate pupillary size in the dark, it is best to dim the room lights and use a ashlight from below to just barely illuminate the eld of both eyes to be able to ascertain the pupil size [6].

Anisocoria that is greater in the dark is seen in certain physiological conditions or Horner’s syndrome. Many factors inuence the pupillary size, such as trauma to the pupillary sphincter or dilator muscle, conditions affecting nerve supply to the iris, and the use of pharmacological agents that dilate or constrict the pupil. Physiological anisocoria is present in about 20% of the population under 17 years of age, and the prevalence increases to 33% in those older than 60 [7].

7.2.2 Pharmacological Tests

forAbnormal Pupils

Performing and interpreting pharmacological tests on abnormal pupils for conditions such as Adie’s tonic pupil (the pupil constricts better to near than to far light) and Horner’s syndrome can aid in diagnosis [8]. However, there are several disadvantages to this approach: (a) the testing conditions must be carefully controlled; (b) the required drugs may not be easily available; (c) tearing, squeezing of eyes, and variable drug penetration can affect the reliability of these tests [4]. The normal pupil of the fellow eye must be used as an internal control for judging the response to these pharmacological agents whenever possible. Therefore, one must always administer the eye drops to both eyes.

Pupillary constriction with diluted pilocarpine (0.0625–0.1%) 30min after instillation is diagnostic of Adie’s tonic pupil. Normal pupils will not constrict at such low concentrations of pilocarpine [9]. In Horner’s syndrome, 2–10% cocaine eye drops induce dilatation of the normal pupil after 40–60 min but do not do so in the affected pupil. However, 0.5–1% apraclonidine eye drops cause dilatation of the affected

(smaller) pupil but will not affect the normal pupil, resulting in a reversal of anisocoria. Hydroxyamphetamine (5%) eye drops can differentiate between pre-ganglionic and postganglionic lesions in proven cases of Horner’s syndrome. Dilatation of the affected pupil an hour after application suggests a pre-ganglionic Horner’s syndrome; dilatation of the normal pupil, but not of the affected pupil, suggests a post-ganglionic lesion [8, 10]. Phenylephrine (2.5%) eye drops also cause mydriasis of Horner’s pupils, which dilates as much as or more than a normal pupil.

7.2.3 Examination ofPupillary Dilation

Dilation lag, or assessment of how quickly the pupils return to their maximal size in the dark, is another important aspect of the pupillary examination. It is guided by sympathetic innervation. To assess pupillary lag, the room lights are turned on very bright and then dimmed to the minimum. Both pupils are observed simultaneously to note how quickly they dilate. The pupils usually reach their maximum size in about 12s, and the maximum dilation happens in the rst 5s; [11] however, this may take up to 25s if dilation lag is present. Dilation lag is a sign of sympathetic denervation or Horner’s syndrome. Infrared videography is invaluable in capturing dilation lag.

7.3 Pupillary Light Reex Examination

Examination of pupillary light reex must ideally be done in a dimly lit room with illumination sufcient to visualize both pupils. The examinee must be instructed to look at a distant target, such as a letter on the distance vision chart at least 3m away, to avoid unwanted pupillary constriction due to accommodation. The examiner then shines a sufciently bright focal light from a pen torch onto the pupils 5–10 cm away from the inferotemporal direction (Fig. 7.1) and observes the

7 The Pupil andPupillary Reexes

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Fig. 7.1 Pupillary constriction response to the light shone on the right eye. The response is seen in the ipsilateral eye (direct light reex) and contralateral eye (consensual light response)

pupillary response [12]. The light source must not interrupt the patient's xation as it will induce pupillary constriction due to the near response. Also, using a too-bright or dim light source may mask or miss some abnormal pupillary responses [13, 14].

The pupillary response in the ipsilateral eye, where the light is directed, is termed the “direct light reex”; the response in the contralateral eye is termed the “consensual light reex” (Fig.7.1). Care must be taken to place one of the examiner’s hands on the patient's nasal bridge while looking at the consensual response to avoid light from crossing over and falling on the contralateral pupil simultaneously; this can lead to erroneous interpretations. Sometimes, another dim and diffuse light source may be placed below the examinee’s face to better observe the consensual reex, especially in individuals with darker irises [15].

The swinging ashlight test (of Levitan) involves rapid rhythmic to-and-fro swinging of the light source between the two eyes [16]. The light is rst shown on one eye for three counts, then swung around to the other eye for three counts, and then swung back. The response of the illuminated pupil is noted as the light is alternated between the two eyes (Fig.7.2). The speed and number of swinging movements can be varied, but care must be taken that the duration of illumination in each eye and the duration of the swinging movement are equal.

7.3.1 Interpretation ofPupillary Light Reexes andSwinging Flashlight Test

The light reex in the pupil is affected in diseases of the anterior part of the afferent limb of the light reex pathway, i.e., primarily in optic nerve disorders. When the afferent pathway is intact, the pupil constricts briskly and equally in response to light in the ipsilateral (direct light reex) and the contralateral eye (consensual light reex) (Fig.7.1). In an afferent pathway defect, the direct and consensual pupillary response to shining the light on the affected eye will be absent or sluggish. However, the direct and consensual light reex response of the contralateral eye will be intact (Fig.7.3). There will be no difference in the pupillary size in afferent pathway defects in ambient light conditions.

When the visual pathway is intact bilaterally, equal pupillary constriction is observed in each eye on the swinging ashlight test (Fig. 7.2). However, when there is an afferent pathway defect, such as optic neuropathy on the one side, there will be apparent dilatation of the affected pupil when light is swung from the normal pupil onto it. This is due to the perceived reduction of input reaching the pretectal region of the midbrain through the abnormal afferent pathway. This is called a relative afferent pupillary defect (RAPD) or Marcus Gunn pupil (Fig.7.4) [17].

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Fig. 7.2 Demonstrating the swinging ashlight test. Pupillary constriction response is equal in each eye, as observed on swinging the light source from one side to the other

M. Swaminathan and G. J. Panicker

Fig. 7.3 A right-sided afferent pathway defect showing no difference in pupil size in ambient light conditions (a) with a reduced direct and consensual light reex response on shining light on the affected (right) pupil (b), while the direct and consensual responses are normal when light is directed on the normal left pupil (c)

There are four grades of RAPD.

RAPD grade 1: Mild pupillary constriction fol-

lowed by greater dilatation (pupillary escape, as described in Marcus Gunn’s original description [18]) when light is swung onto the abnormal eye [19].

RAPD grade 2: There is no initial pupillary

movement (pupillary stall) followed by dilatation.

RAPD grade 3: The abnormal pupil will dilate

immediately.

RAPD grade 4: An amaurotic or deafferented

pupil, xed and dilated [20].

Another method of grading RAPD is by using graded neutral density lters over the normal eye and performing the swinging ashlight test till there is an equal response in both eyes [21]. Bell etal. described a clinical grading system corresponding to the neutral density lter grading of RAPD.In this, grade I is when a weak initial constriction followed by greater re-dilatation occurs; grade II is when an initial stall occurs followed

7 The Pupil andPupillary Reexes

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by greater re-dilatation; grade III is when an immediate pupillary dilatation occurs; grade IV is when an immediate pupillary dilatation following prolonged illumination of the good eye for 6s occurs, and grade V is when an immediate pupillary dilatation with no secondary constriction occurs [22]. However, in common clinical practice, only recording the presence/absence of RAPD is done; usually, grading may not be done.

Given that this is a “relative” test, there must

be a signicant asymmetry between the visual

Fig. 7.4 A left relative afferent pupillary defect is where there is paradoxical dilatation of the affected left pupil on swinging the ashlight from the normal right pupil

pathways for a RAPD to manifest, and there can never be a bilateral RAPD, even in bilateral damage to the afferent pathways. In some cases where one pupil is non-reacting due to trauma or efferent damage, a swinging ashlight test can still be done to detect the afferent pupillary defect in the same eye. In this situation, when light is directed on the affected pupil, there will be dilatation of the contralateral normal pupil. This is known as “reverse” RAPD [20] (Fig.7.5).

Fig. 7.5 When the left pupil is non-reacting (e.g., third nerve palsy or traumatic mydriasis) and there is a coexistent left afferent pathway defect, paradoxical dilatation of the normal right pupil is seen when light is swung onto the affected left side; this is known as reverse RAPD

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M. Swaminathan and G. J. Panicker

One should suspect a refractive error, amblyopia, media opacity, functional visual loss, or vision loss in the other eye when vision is reduced in one eye and there is no RAPD.Though there are reports of RAPD in a few cases of unilateral amblyopia, it is usually mild (<0.6 log units) and does not correlate with visual acuity. This could be due to visual cortical decit, which secondarily affects the afferent pathways and the retina in some amblyopes [23]. Hippus, dened as the physiological uctuation in pupil diameter under constant light conditions, should not be mistaken for a RAPD [24].

7.4 Near Response

Pupillary response to a near target is part of the triad of accommodation and convergence. This is best performed in a fairly well-lit room so that the examiner sees pupils easily. It is advisable not to use any other handheld light source to visualize the pupils, as the pupillary response to light may confuse the picture. An accommodative target with details would be the Ideal target for the patient to look at. It is better to avoid pen, pencil, etc. In a blind patient, the patient’s own ngers may be used as a target. The patient is instructed to look at a vision chart located at 3 or 6 meters and then instructed to turn their gaze to the near target briskly while examining the pupillary construction.

7.4.1 Light Near Dissociation

This term describes the condition when the pupillary light response is impaired, but the near response is normal or almost normal. Several causes are known for this, which include blindness from optic nerve or retinal damage, oculomotor nerve paralysis with aberrant regeneration, neurosyphilis, hydrocephalus, pontine tumors, and tonic pupils such as Adie’s pupil. Hence it is important to examine for the intact near pupillary response in any patient with impaired light response. It is extremely rare to nd the light response is preserved, but the near response is

impaired. The commonest cause is not making a good voluntary accommodative effort to the near target by the patient.

7.5 Slit Lamp Examination ofthePupil

The pupils' size, shape, and location must also be examined using a slit lamp to detect the presence of any abnormalities.

1. Size: Pupillary size can be measured using a

pupil gauge or millimeter rule or on the slit lamp. Normally, the pupils are equal in size, around 3–6mm in bright light and 4–8mm in dim light [12]. A difference in pupil size between the two eyes (>0.4 mm) is called anisocoria.

2. Shape: The pupils are normally round in

shape. Other shapes include festooned pupil, tadpole pupil, keyhole pupil, and irregular or oval pupil. Festooned pupils are seen in iritis, where the posterior synechiae distort the pupil shape; it is more evident after dilatation. Irregular, oval, or slit-like pupils may be congenitally present in anterior segment dysgenesis syndromes or acquired after trauma, surgery, or due to neurological diseases [25]. Tadpole-shaped pupils are seen due to segmental spasms of the iris dilator muscle, which may accompany migraine or ipsilateral Horner’s syndrome [26]. Iris coloboma is an inferior or inferonasal notch in the pupil (keyhole appearance), which may be accompanied by chorioretinal colobomas [27].

3. Location: The normal pupil is centrally

located. Corectopia is a condition where the pupil is eccentric inlocation. This can be seen in anterior segment dysgenesis syndromes, iridocorneal endothelial syndromes, chronic uveitis, trauma, and postoperatively and congenitally in ectopia lentis et pupillae (corectopia associated with lens subluxation) [25].

4. Congenital anomalies like persistent pupillary

membranes may also be seen on the slit lamp. Characteristic spoke-like remnants of the tunica vasculosa lentis are seen across the

7 The Pupil andPupillary Reexes

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pupil. These vary in size and density and are usually visually insignicant [28].

5. The pupillary light reaction can also be tested on the slit lamp by measuring the edge pupillary cycle time [29]. A thin optical slit is placed on the edge of the pupil, which induces pupillary constriction causing the pupil to move out of the slit section. Subsequently, as the illumination decreases, the pupil dilates until the edge again reaches the optical slit. Twenty-ve such cycles are timed and noted. The edge pupil cycle time increases in afferent pathway defects [30].

6. Pupillary movements: The normal pupil shows small amounts of dilatation and constriction under steady illumination. This constant movement or restlessness of the pupil is called hippus or pupillary unrest. It is more prominent in bright light and younger individuals [31]. Vermiform movements (worm- like movements) and sectoral paralysis (immobility of parts of the pupil) are seen on slit lamp examination of Adie’s tonic pupils [32].

7.6 Other Pupillary Phenomena

1. Westphal–Piltz Reex: Pupillary constriction in darkness during sleep is considered normal. This phenomenon is called the Westphal–Piltz reex. It is thought to be secondary to decreased parasympathetic inhibition [20].

2. Paradoxical Pupillary Constriction in the dark: When the lights are turned off, there is initial miosis followed by slow dilatation; this phenomenon is seen in retinal dystrophies like congenital stationary night blindness or achromatopsia. A child with such paradoxical pupillary constriction, poor vision, nystagmus, or a family history of retinal disorders should undergo electroretinography [33].

3. Tournay’s Pupillary Phenomenon: This refers to pupil dilatation on the abduction of the ipsilateral eye. It is seen in up to 10% of the normal population and is thought to be due to anomalous innervation [34].

4. Idiopathic Alternating Anisocoria: It is a rare condition in which the pupils dilate one at a time, alternatingly every few hours [35].

7.7 Conclusion

A thorough examination of the pupils and the pupillary reexes must be done for every patient visiting an eye clinic. Apart from gaining vital information regarding the integrity of the afferent and efferent limbs of the light reex pathway, pupil examination can also provide vital clues on several underlying ocular and neurological conditions.

Disclosure None.

References

1. Jacobson DM.Benign episodic unilateral mydriasis. Ophthalmology. 1995;102:1623–7.

2. Murray RB, Adler MW, Korczyn AD.The pupillary effects of opioids. Life Sci. 1983;33:495–509.

3. Weir REP, Whitehead DEJ, Zaid FH, et al. Pupil blown by a puffer. Lancet. 2004;363:1853.

4. Digre KB.Walsh and Hoyt’s clinical neurophthalmology. 6th ed.; 2005. pp.715–38.

5. Wachler BSB, Krueger RR. Agreement and repeatability of infrared pupillometry and the comparison method. Ophthalmology. 1999;106:319–23.

6. Ettinger ER, Wyatt HJ, London R.Anisocoria: variation and clinical observation with different conditions of illumination and accommodation. Invest Ophthalmol Vis Sci. 1991;342:501–9.

7. Lam BL, Thompson HS, Corbett JJ. The prevalence of simple anisocoria. Am J Ophthalmol. 1987;104:69–73.

8. Antonio-Santos AA, Santo RN, Eggenberger ER. Pharmacological testing of anisocoria. Expert Opin Pharmac. 2005;6(12):2007–13.

9. Leavitt JA, Wayman LL, Hodge DO, et al. Pupillary response to four concentrations of pilocarpine in normal subjects: application to testing for Adie tonic pupil. Am J Ophthalmol. 2002;133:333–6.

10. Brown SM, Aouchiche R, Freedman KA.The utility of 0.5% apraclonidine in the diagnosis of Horner syndrome. Arch Ophthalmol. 2003;121:1201–3.

11. Pilley SFJ, Thompson HS. Pupillary “dilation lag” in Horner’s syndrome. Br J Ophthalmol. 1975;59:731–5.

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