AUTHOR AND EDITOR INFORMATION

Section 1 of 9  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• References

INTRODUCTION

Section 2 of 9  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• References

Background

Alacrima refers to a wide spectrum of lacrimal secretory disorders that are mostly congenital in origin. Symptoms of these disorders can range from a complete absence of tears to hyposecretion of tears; symptoms of rarer disorders include a selective absence of tearing in response to emotional stimulation but a normal secretory response to mechanical stimulation.

Pathophysiology

The disorder is usually inherited in an autosomal recessive fashion, but dominant pedigrees have been described. Mutations in the AAAS gene on chromosome band 12q13 have been described in several pedigrees with Allgrove (or triple-A) syndrome. The AAAS gene encodes a 547-amino acid protein named ALADIN (for alacrima-achalasia-adrenal insufficiency-neurologic disorder), which belongs to the family of regulatory proteins that play an important role in regulating intracellular protein transport.¹

Etiologies can be separated into pathological mechanisms or syndromic associations. See Causes.

Frequency

United States

Uncommon

International

Uncommon

Mortality/Morbidity

Corneal sequelae are the most feared complication.

Age

Onset of this condition occurs in infancy.

CLINICAL

Section 3 of 9  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• References

History

• Patients with alacrima can have a wide spectrum of clinical presentations, from entirely asymptomatic and comfortable to presenting with debilitating symptoms of foreign body sensation, photophobia, ocular pain, and decreased visual acuity.
• Parents may notice that there is a history of crying without tears since birth.
• Information obtained from the history may be significant when alacrima is syndromic and associated with other findings.

Physical

Physical findings may be either ocular or systemic.

• Eyelids - Chronic blepharoconjunctivitis
• Tear film - Decreased/absent tear production
• Conjunctiva - Hyperemia, thick mucoid discharge
• Cornea - Hypesthesia, interstitial keratitis, pannus, subepithelial opacities, infectious ulcers, corneal perforations
• Extraocular muscles - Palsies of cranial nerves III, IV, and VI
• Pupils - Anisocoria, tonic pupils
• Optic nerve - Optic atrophy
• Orbit – Absence of the palpebral lobe of the lacrimal gland
• Systemic findings
• • Gastrointestinal - Xerostomia, achalasia, decreased salivation
  • Neurologic - Peripheral and autonomic neuropathy
  • Musculoskeletal - Osteoporosis, short stature
  • Metabolic - Adrenocortical insufficiency

Causes

Etiologies can be separated into pathological mechanisms or syndromic associations.

• Mechanism
• • Nuclear aplasia
  • Failure of central nervous system/peripheral nervous system (CNS/PNS) innervation
  • Lacrimal gland aplasia/hypoplasia
• Syndromic
• • Isolated congenital alacrima
  • Riley-Day syndrome - Familial dysautonomia
  • Anhidrotic ectodermal dysplasia - Decreased sweating and salivation, heat intolerance, hypotrichosis
  • Sjögren syndrome - Xerostomia, salivary gland enlargement, collagen-vascular disease association
  • Allgrove (or triple-A) syndrome - Achalasia, alacrima, adrenocorticotropic hormone (ACTH) insensitivity, late neurologic manifestations

DIFFERENTIALS

Section 4 of 9  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• References

WORKUP

Section 5 of 9  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• References

Imaging Studies

• CT scan of the orbits - Aplastic/hypoplastic lacrimal glands

Procedures

• Neostigmine testing can be performed as a challenge to evaluate for the presence of secondary tear production.
• • Dosages vary but can be calculated with this formula: [Weight (kg)/70] X 1.5 mg = dose
  • The patient may be reexamined 30-45 minutes later for evidence of tear production. Typically, no secondary tear production is seen in patients with alacrima.
• Schirmer testing
• • This secretory test is used in the evaluation of patients with alacrima. Testing can be performed to test for basal secretors or for combined basal and reflex secretors. Schirmer test strips are specially prepared Whatman #41 paper, each measuring 35 mm in length and 5 mm in width. A notch is located 5 mm from the end to facilitate bending and placement in the conjunctival fornix. After placement in the fornix, tears advance via capillarity and reflect the tear production of the eye.
  • For basal secretor testing, a drop of topical anesthetic is placed in the conjunctival fornix. The inferior fornix should be dried with a cotton-tipped applicator. The Schirmer test strip is bent at the 5 mm notch and placed in the central lid of each eye. The strips are removed at 5 minutes, and a pen mark is placed at the junction of the wet test strip and the dry test strip. A measurement is made between the mark and the 5 mm notch. A normal value is 10 mm of wetting at 5 minutes, with lower values indicating a dry eye condition. Of asymptomatic patients, 15% have values of less than 3 mm.
  • For basal and reflex secretor testing, no topical anesthetic is used. The inferior fornix should be dried with a cotton-tipped applicator. The test is carried out as outlined above, and the normal median wetting approximates 15 mm, with a range of 10-30 mm. A value of less than 5 mm is abnormally low.
• Conjunctival and lacrimal gland biopsy specimens may be of value to identify underlying histopathologic findings.

Histologic Findings

Conjunctiva biopsy specimens reveal hydropic epithelial degeneration. Lacrimal gland biopsy specimens may reveal neuronal degeneration and depletion of dense core vesicles.

TREATMENT

Section 6 of 9  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• References

Medical Care

• Artificial tears are used as the primary treatment modality as often as necessary to relieve ocular discomfort.
• Severe cases necessitate more viscous preparations, such as gels and ointments.
• Pay particular attention to preservatives and concomitant hypersensitivity.
• Petrolatum gels may be used at night.
• Progressive symptoms may require sustained-release ocular inserts.
• Moisture chambers at night may be attempted, but compliance in children is often poor.
• • Blepharoconjunctivitis may be treated with hot compresses and antibiotic drops or ointments.
  • Some cases of keratoconjunctivitis sicca, especially with recurrent corneal erosion or ulceration, may be ameliorated with bandage contact lenses, aggressive topical lubrication, and antibiotics (as needed).
  • Cases of systemic autoimmune dysfunction have been treated with neostigmine (Prostigmin).
  • Corneal epithelial breakdown is more likely if the cornea is anesthetic.

Surgical Care

Attempt surgical interventions when conservative topical therapy does not relieve symptoms.

• Temporary occlusion
• • Temporary punctal obliteration is difficult to quantitate and better achieved by punctal plugs.
  • If surgical obliteration is contemplated, it probably should be permanent.
• Permanent occlusion
• • Permanent punctal occlusion should be attempted if all conservative means fail.
  • Inferior punctal occlusion and/or superior punctal occlusion may be attempted depending on the severity of the clinical findings.
  • Thermal, electrical, and laser modalities have been advocated, but the best permanent results occur when the punctum and the vertical limb of the canaliculus are obliterated.
• Tarsorrhaphy: Temporary or permanent tarsorrhaphy is indicated with prolonged symptoms or evidence of ocular compromise characterized by corneal breakdown.

Consultations

Consider consultation with a neurologist and a pediatrician.

MEDICATION

Section 7 of 9  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• References

The goals of pharmacotherapy are to reduce morbidity and to prevent complications.

Drug Category: Acetylcholinesterase inhibitors

Inhibit the cholinesterase-induced breakdown of acetylcholine, thus allowing enhanced transmission across the neuromuscular junction.

FOLLOW-UP

Section 8 of 9  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• References

Further Outpatient Care

• Instruct patients to return if they experience either of the following:
• • They remain symptomatic despite their current treatment regimen.
  • They begin to develop new symptoms.

Complications

• Disease-related complications include the following:
• • Keratoconjunctivitis sicca
  • Corneal decompensation
  • Recurrent corneal erosion
  • Bacterial keratitis
• Treatment-related complications that may occur with punctal plugs include the following:
• • Local irritation
  • Epiphora
  • Plug extrusion
  • Canaliculitis
  • Recurrent dacryocystitis

Prognosis

• Long-term follow-up care is essential because of the possible development of keratoconjunctivitis sicca and corneal decompensation.
• When associated with systemic disease, the condition can be fatal due to secondary autonomic and endocrine dysfunction.

REFERENCES

Section 9 of 9

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• References

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2. Akova YA, Demirhan B, Cakmakci S, Aydin P. Pyogenic granuloma: a rare complication of silicone punctal plugs. Ophthalmic Surg Lasers. Jul-Aug 1999;30(7):584-5. [Medline].
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4. Babu K, Murthy KR, Babu N, Ramesh S. Triple A syndrome with ophthalmic manifestations in two siblings. Indian J Ophthalmol. Jul-Aug 2007;55(4):304-6. [Medline].
5. Davidoff E, Friedman AH. Congenital alacrima. Surv Ophthalmol. Sep-Oct 1977;22(2):113-9. [Medline].
6. Gazarian M, Cowell CT, Bonney M, Grigor WG. The "4A" syndrome: adrenocortical insufficiency associated with achalasia, alacrima, autonomic and other neurological abnormalities. Eur J Pediatr. Jan 1995;154(1):18-23. [Medline].
7. Hegab SM, al-Mutawa SA. Congenital hereditary autosomal recessive alacrima. Ophthalmic Genet. Mar 1996;17(1):35-8. [Medline].
8. Kinjo S, Takemoto M, Miyako K, Kohno H, Tanaka T, Katsumata N. Two cases of Allgrove syndrome with mutations in the AAAS gene. Endocr J. Oct 2004;51(5):473-7. [Medline].
9. Mondino BJ, Brown SI. Hereditary congenital alacrima. Arch Ophthalmol. Sep 1976;94(9):1478-84. [Medline].
10. Moore PS, Couch RM, Perry YS, Shuckett EP, Winter JS. Allgrove syndrome: an autosomal recessive syndrome of ACTH insensitivity, achalasia and alacrima. Clin Endocrinol (Oxf). Feb 1991;34(2):107-14. [Medline].
11. Mullaney PB, Weatherhead R, Millar L, Ayyash II, Ayberk H, Cai F, et al. Keratoconjunctivitis sicca associated with achalasia of the cardia, adrenocortical insufficiency, and lacrimal gland degeneration: Keratoconjunctivitis sicca secondary to lacrimal gland degeneration may parallel degenerative changes in esophageal and adrenocortical function. Ophthalmology. Apr 1998;105(4):643-50. [Medline].
12. Ornek K, Atilla H, Zilelioglu G. Pediatric alacrima, achalasia, and mental retardation. J AAPOS. Aug 2002;6(4):261-3. [Medline].
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15. Smith RS, Maddox SF, Collins BE. Congenital alacrima. Arch Ophthalmol. Jan 1968;79(1):45-8. [Medline].
16. Uleckas JK, Garel L, Milot J, Mathieu-Millaire F. Orbital CT scan in congenital alacrima. J Pediatr Ophthalmol Strabismus. Mar-Apr 1994;31(2):114-7. [Medline].
17. Weber A, Wienker TF, Jung M, Easton D, Dean HJ, Heinrichs C, et al. Linkage of the gene for the triple A syndrome to chromosome 12q13 near the type II keratin gene cluster. Hum Mol Genet. Dec 1996;5(12):2061-6. [Medline].
18. Yoshita T, Kobayashi A, Sugiyama K. Bilateral corneal perforation in an infant with congenital alacrima. J Pediatr Ophthalmol Strabismus. Jul-Aug 2006;43(4):236-8. [Medline].

Article Last Updated: Nov 7, 2007