Holmes-Adie Syndrome is a relatively common neurological disorder characterized by a triad of symptoms: unilateral or bilateral tonically dilated pupils with light-near dissociation, tendon areflexia, and may be associated with hypohidrosis. It is mostly idiopathic and results from damage to the ciliary ganglion, though it can be caused by infections, ischemia, or autoimmune disorders. Diagnosis is made through history, physical exam, and pharmacologic testing. Prognosis is generally good as the syndrome does not progress over time, though complications like angle-closure glaucoma can rarely occur.

1. Holmes-Adie Syndrome
Ade Wijaya, MD – October 2020

2. Introduction
• Holmes- Adie Syndrome / Adie Syndrome
• Introduced in 1931 by William John Adie, the British neurologist
of Australian descent, and Sir Gordon Morgan Holmes, an Irish
neurologist
• Relatively common neurological disorder of unknown etiology
Adie WJ. PSEUDO-ARGYLL ROBERTSON PUPILS WITH ABSENT TENDON REFLEXES: A BENIGN DISORDER SIMULATING TABES DORSALIS. Br Med J.1931 May 30;1(3673):928-30.

3. Clinical Presentation
Unilateral or bilateral tonically
dilated pupils
Light-near dissociation
Tendon areflexia
Sarao MS, Elnahry AG, Sharma S. Adie Syndrome (Tonic Pupil Syndrome) [Updated 2020 Jul 11]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2020
Can be associated with hypohidrosis, in this case, it is known as Ross syndrome

4. Epidemiology
• Incidence: 4.7/100,000 population/year
• Prevalence: 2/1000 population
• Age: 25 to 45 (mean age of 32 years)
• Female > Male
• 80 % unilateral
Sarao MS, Elnahry AG, Sharma S. Adie Syndrome (Tonic Pupil Syndrome) [Updated 2020 Jul 11]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2020

5. Etiology : Mostly idiopathic
May rarely be caused by local
disorders involving the orbit that affect the
ciliary ganglion including
• Infections such as syphilis,
varicella, human parvovirus-B19, human
immunodeficiency virus, and Lyme disease
• Ischemia due to lymphomatoid
granulomatosis, migraine, and giant cell
arteritis
• Autoimmune disorders such as Sjogren
syndrome, polyarteritis nodosa,
sarcoidosis, amyloidosis, Guillain-Barre
syndrome, and Vogt-Koyanagi-Harada
disease
• Cardiovascular disorders
• Local or general anesthesia
• Orbital or choroidal tumors
• Orbital surgery for orbital floor fractures
• Neuromuscular conditions such as
Lambert-Eaton myasthenic syndrome,
• Paraneoplastic in association with anti-Hu
antibodies
• Retinal photocoagulation that results in
damage to the ciliary nerves within the
suprachoroidal space.
• Familial dysautonomia
Sarao MS, Elnahry AG, Sharma S. Adie Syndrome (Tonic Pupil Syndrome) [Updated 2020 Jul 11]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2020

6. Pathophysiology
• Damage to the ciliary ganglion most commonly by an inflammatory
process.
Sarao MS, Elnahry AG, Sharma S. Adie Syndrome (Tonic Pupil Syndrome) [Updated 2020 Jul 11]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2020

7. Oculomotor Nerve Pathway

8. Histopathology
• Ciliary ganglion on the affected side has degenerated with associated
partial atrophy of the sphincter pupillae muscle
• There was also minimal neuronal degeneration affecting the superior
cervical ganglion, the sacral dorsal root ganglion, and the sciatic nerve
Sarao MS, Elnahry AG, Sharma S. Adie Syndrome (Tonic Pupil Syndrome) [Updated 2020 Jul 11]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2020

9. Diagnosis
• History and physical
• Pharmacologic Testing: cholinergic denervation supersensitivity with low
concentration pilocarpine
• Sweat testing
• Etiologic Evaluation
Sarao MS, Elnahry AG, Sharma S. Adie Syndrome (Tonic Pupil Syndrome) [Updated 2020 Jul 11]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2020

10. Differential Diagnosis
• Argyll Robertson pupil
• Ross and Harlequin syndromes
• Horner Syndrome
Sarao MS, Elnahry AG, Sharma S. Adie Syndrome (Tonic Pupil Syndrome) [Updated 2020 Jul 11]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2020

11. Treatment
• Most do not require any treatment
• Treat underlying conditions if any
• Reading glasses
• Topical low-dose pilocarpine or physostigmine drops
• Thoracic sympathectomy is the treatment of choice for diaphoresis
• Interdisciplinary approach
Serra Mitjans M, Callejas Pérez MA, Valls Solé J, Grimalt Santacana R, Rubio Garay M, Iglesias Sentís M. [Surgical treatment for compensatory hyperhidrosis in Adie syndrome].Arch. Bronconeumol. 2004 Feb;40(2):97-9
Sarao MS, Elnahry AG, Sharma S. Adie Syndrome (Tonic Pupil Syndrome) [Updated 2020 Jul 11]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2020

12. Prognosis and Complication
• Good prognosis
• Does not have a progressive course
• The pupil light reaction becomes weaker over time with an increasing
light-near dissociation, and the pupil becomes smaller with time ("little
old Adie")
• May rarely result in angle-closure glaucoma
• May cause amblyopia in children
Sarao MS, Elnahry AG, Sharma S. Adie Syndrome (Tonic Pupil Syndrome) [Updated 2020 Jul 11]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2020

13. Summary
• Triad: unilateral or bilateral tonically dilated pupils with light-near
dissociation and tendon areflexia
• Mostly idiopathic
• Good prognosis; no progression
• May rarely develop into angle-closure glaucoma
• Interdisciplinary approach

14. THANK YOU