This document provides information on common abnormalities of pupillary reflexes, including Adie's (tonic) pupil, Argyll Robertson pupils, Horner's syndrome, and anisocoria. It defines each condition, describes associated signs and symptoms, potential causes, diagnostic testing, and treatment considerations. Prof. Dr. Hussain Ahmad Khaqan provides details on evaluating pupils using slit lamp examination and pharmacological testing to differentiate various conditions causing pupillary reflex abnormalities.

1. Pupillary Reflexes; Common Abnormalities
Prof. Dr. Hussain Ahmad Khaqan
 MD
 FRCS(Glasgow)
 FCPS(Ophth.)
 FCPS(Vitreo Retina)
 MHPE (KMU)
 CICO(UK)
 CMT(UOL)
 Fellowship in Medical Retina (LMU, Munich)
 Fellowship in Vitreo Retinal Surgery (LMU, Munich)
 Consultant Ophthalmologist & Retinal Surgeon
Professor of Ophthalmology
Lahore General Hospital, Lahore
Ameer Ud Din Medical College, Lahore
Post Graduate Medical Institute, Lahore
Shaukat Khanum Memorial Cancer Hospital & Research Centre ,Lahore

2. ADIE (TONIC) PUPIL

3. DEFINITION
• In Adie’s pupil, the parasympathetic supply from the
ciliary ganglion to the iris and ciliary muscle is
abnormal due to acute viral denervation and
aberrant regeneration

4. SYMPTOMS
• Difference in size of pupils
• Blurred near vision
• Photophobia
• May be asymptomatic.

5. SIGNS
• Classically, pupil is mydriatic, poor response to light, with
vermiform movements seen at the slit-lamp, and exaggerated,
but slow and sustained (tonic), response to near/light-near
dissociation.
• Variants: early lesions may show no response to light or near;
late lesions are usually miotic; segmental lesions are common;
there may be additional absence of deep tendon reflexes
(holmes–Adie syndrome) or patchy hypohidrosis (Ross
syndrome); with time, the pupil becomes miotic.

6. CAUSES
• Idiopathic most commonly. Orbital trauma, surgery, and
varicella zoster infection are seen frequently. Early
syphilis, parvovirus B19, herpes simplex virus, botulism,
paraneoplastic syndrome, giant cell arteritis (GCA), pan-
retinal photocoagulation, and neurologic Lyme disease less
commonly. Rare associations reported with endometriosis,
seminomas, and Sjögren syndrome.

7. DIFFERENTIAL DIAGNOSIS
• Parinaud syndrome/dorsal midbrain lesion: Bilateral mid-
dilated pupils that react poorly to light but constrict normally
with convergence (not tonic). Associated with eyelid
retraction (Collier sign), supranuclear up gaze paralysis, and
convergence retraction nystagmus. An MRI should be
performed to rule out pinealoma and other midbrain
pathology.
• Holmes–Adie syndrome: Tonic pupil and tendon areflexia.
May be associated with autonomic and peripheral
neuropathy.
• Argyll Robertson Pupils

8. INVESTIGATIONS
• Evaluate pupils and iris at slit lamp or with a muscle light for
irregular slow constriction or abnormal movement.
• Test for cholinergic hypersensitivity. Instill 0.125% pilocarpine
in both eyes and recheck pupils in 10 to 15 minutes. An Adie
pupil constricts while the normal pupil does not.
• If bilateral simultaneous Adie pupils, consider further
laboratory investigations including testing for the
aforementioned etiologies.
• If Adie pupil is present in a patient younger than 1 year,
consult a pediatric neurologist to rule out familial
dysautonomia (Riley–Day syndrome).

9. TREATMENT
• Reassure patient.
• Weak-strength pilocarpine (e.g. 0.1%, as often as required)
may help treat mydriatic blurring and accommodative
problems.
• Mydriasis may also be helped by a painted CL (contact lens)
acting as an artificial pupil.
• Reading glasses may also help with the accommodative
dysfunction

10. ARGYLL ROBERTSON PUPILS

11. CLINICAL FEATURES
• Initially unilateral, then bilateral, irregular miosed
pupils.
• React poorly to light.
• Light-near dissociation.
• Iris can be atrophic on slit-lamp examination.

12. CAUSES
• Tertiary syphilis.

13. DIFFERENTIAL DIAGNOSIS OF “LIGHT-NEAR” DISSOCIATION
• Bilateral optic neuropathy or severe retinopathy: Reduced
visual acuity with normal pupil size.
• Adie (tonic) pupil: Unilateral or bilateral irregularly dilated
pupil that constricts slowly and unevenly to light. Normal
vision.
• Dorsal midbrain (Parinaud) syndrome: Associated with eyelid
retraction (Collier sign), supranuclear up gaze palsy, and
convergence retraction nystagmus.
• Rarely caused by third nerve palsy with aberrant
regeneration.
• Others: Diabetes, alcoholism, etc.

14. INVESTIGATIONS
• Test the pupillary reaction to light and convergence
• Slit lamp examination
• Dilated fundus examination
• Non-treponemal serology
• Treponemal serology
• If the diagnosis of syphilis is established, lumbar puncture (LP)
may be indicated.

15. TREATMENT
• Management of syphilitic eye disease should be in
conjunction with a GU (genitourinary) physician.
• Benzathine benzyl penicillin, with an extended regimen for
late latent and tertiary syphilis.

16. HORNER’S SYNDROME

17. INTRODUCTION
• The ocular sympathetic supply may be damaged anywhere
along its route. The extent of sympathetic dysfunction,
associated neurological signs, and pharmacological tests help
to identify the level of the injury.

18. SYMPTOMS
• Dropping of eyelid
• Different sized pupil
• Decreased or loss of sweating
• Often asymptomatic.

19. SIGNS
• Pupil is miotic with normal light and near reaction.
• Anisocoria is most marked in dim conditions.
• Also ptosis, apparent enophthalmos (due to 1–2mm upper lid
ptosis and 1mm elevation of lower lid); (“reverse ptosis”),
lower IOP, conjunctival hyperemia due to decreased episcleral
vascular tone. Facial anhydrosis suggests lesion of the first- or
second-order neurone; iris hypochromia suggests a congenital
lesion (also in long-standing acquired lesions). Transient
increase in accommodation (older patients hold their
reading card closer in the Horner eye).

20. Figure: Right Horner syndrome with ptosis and miosis.

21. CAUSES
• First-order neuron disorder: Stroke (e.g. , vertebrobasilar artery
insufficiency or infarct), tumor, multiple sclerosis (MS). Rarely,
severe osteoarthritis of the neck with bony spurs.
• Second-order neuron disorder: Tumor (e.g. , lung carcinoma,
metastasis, thyroid adenoma, neurofibroma), aortic aneurysm
(e.g. , tertiary syphilis). Patients with pain in the arm or scapular
region should be suspected of having a Pancoast tumor. In
children, consider neuroblastoma, lymphoma, or metastasis.
• Third-order neuron disorder: Headache syndrome (e.g. , cluster,
migraine, Raeder paratrigeminal syndrome), internal carotid
dissection, varicella zoster virus, otitis media, Tolosa–Hunt
syndrome, neck trauma/tumor/inflammation, cavernous sinus
pathology.
• Congenital Horner syndrome: May also be caused by birth trauma.
• Other rare causes: Cervical paraganglioma, ectopic cervical
thymus.

22. INVESTIGATIONS
• Diagnosis confirmed by a relative reversal in anisocoria with
apraclonidine (0.5% or 1%). The miotic pupil with Horner syndrome
will appear larger than the normal pupil after apraclonidine
instillation.
• A third-order neuron disorder may be distinguished from a first-
and second-order neuron disorder with hydroxyamphetamine.
• Complete blood count (CBC) with differential.
• Computed tomography (CT) of the chest to evaluate lung apex for
possible mass (e.g. , Pancoast tumor).
• Magnetic resonance imaging (MRI) of the brain and neck.
• Lymph node biopsy when lymphadenopathy is present.

23. TREATMENT
• This is dependent on the underlying cause and may involve
urgent referral to other specialties.
• In cases associated with cluster headaches (Raeder
syndrome), recovery may occur within a few hours.
• Ptosis surgery may be performed electively

24. Congenital Horner’s syndrome

25. CAUSES
• Usually idiopathic
• Birth trauma (such as forceps delivery).
• Is either parasympathetic insufficiency of the iris
sphincter, or sympathetic hyperactivity of the iris
dilator.

26. CLINICAL FEATURES
• Miosis, ptosis, and apparent enophthalmos.
• Heterochromia: lighter iris pigmentation on
ipsilateral side.
• Facial flushing (‘harlequin’ sign), particularly seen on
cycloplegic refraction or crying, due to ipsilateral
anhydrosis. Generally, the affected side is pale.

27. CAUTION
• Acquired horner’s syndrome in childhood should be
investigated for neuroblastoma.

28. ANISOCORIA

29. CLASSIFICATION
• The abnormal pupil is constricted.
• The abnormal pupil is dilated.
• Physiologic anisocoria

30. WORK-UP
• History
• Ocular examination:
• If the abnormal pupil is small, a diagnosis of Horner
syndrome may be confirmed by a cocaine or apraclonidine
test. In the presence of ptosis and an unequivocal increase in
anisocoria in dim illumination, cocaine and apraclonidine
testing may be unnecessary.

31. • If the abnormal pupil is large and there is no sphincter muscle
damage or signs of third nerve palsy (e.g. , extraocular
motility deficit, ptosis), the pupils are tested with one drop
of pilocarpine 0.125%. Within 10 to 15 minutes, an Adie
pupil will constrict significantly more than the fellow pupil.
WORK-UP