Article

DRY EYE DX AND TX

A LOOK AT ALAGILLE SYNDROME

I recently examined a 41-year-old male patient who reported that his eyes were red with a mild discharge, especially the left eye; it was worse upon awakening and had been occurring for two weeks. His daughter had been treated with gentamicin solution for “conjunctivitis” one month prior to his own symptoms.

Upon examination, the patient’s left eye was mildly, diffusely injected, the cornea without stain, and the anterior chambers were quiet. Of note, both eyes had nasal conjunctival staining. The lower eyelids were lax, with slow snap-back; nasally, the apposition of the lower eyelids to the globe was poor in both eyes. There was a hint of lagophthalmos in the left eye. A scant discharge was present in the left eye, with a mild papillary reaction and a number of concretions in both eyes. No pre-auricular node (PAN) was palpable. This mildly amblyopic, anisometropic hyperope reported no history of contact lens wear.

The patient’s medical history was notable for Alagille syndrome. Also known as Alagille-Watson syndrome, this multisystem, variably expressed, autosomal-dominantly inherited disorder is associated with abnormalities of the liver, heart, skeleton, kidneys, and eyes.

Signs and Symptoms

The incidence of Alagille syndrome is approximately 1 in 30,000 to 45,000 individuals in the general population (https://rarediseases.org ). A small percentage of patients have intellectual disability (Neiberg and Lee, 2012). Individuals who have Alagille syndrome usually have distinctive facial features that include low, deep-set, widely spaced eyes (hypertelorism), a pointed chin, straight nose with a flattened tip, and a broad forehead. In older individuals and adults, the chin may appear prominent. The overall appearance of the face is of an inverted triangle (Kamath et al, 2002).

A primary feature of Alagille syndrome is liver damage caused by abnormalities in the bile ducts. The bile ducts may be narrow, malformed, and reduced in number; bile builds up in the liver and causes scarring that prevents the liver from properly eliminating wastes from the bloodstream. Signs and symptoms of liver damage in Alagille syndrome may include a yellowish tinge in the skin and the whites of the eyes (jaundice), itchy skin from increased bilirubin (bile is pigmented with bilirubin), and deposits of cholesterol in the skin (xanthomas) (https://ghr.nlm.nih.gov ).

Alagille syndrome is also associated with several heart problems, including impaired blood flow from the heart into the lungs (pulmonic stenosis). This may occur along with a hole between the two lower chambers of the heart (ventricular-septal defect) and other heart abnormalities (https://ghr.nlm.nih.gov ). Individuals who have Alagille syndrome can also develop vascular anomalies in the brain, liver, lungs, heart, and kidneys. Vascular anomalies in the brain can lead to intracranial bleeding and stroke (https://rarediseases.org ). In addition, the bones of the spinal column may have an unusual butterfly shape.

The most common ocular abnormalities are posterior embryotoxon, iris abnormalities (Axenfeld anomaly/mosaic iris stromal hypoplasia), diffuse fundus hypopigmentation, speckling of the retinal pigment epithelium, and optic disc drusen. Optic pits and serous macular detachment can occur (Nischal et al, 1997). Decreased axial length and microcornea are common (Brodsky and Cunniff, 1993).

Searching for Answers

Was I looking at an exposure-based dry eye secondary to syndrome-related deep-set eyes in this patient? If so, what was the tipping point for the red-eye manifestation? Embryotoxon is not an indicator of Alagille syndrome, but if present, the anterior chamber should be carefully evaluated and the patient monitored for glaucoma.

When Alagille syndrome is suspected, refer patients for full systemic workup including imaging, genetic workup, and counseling. Should dry eye be added to the Alagille syndrome complication list? CLS

For references, please visit www.clspectrum.com/references and click on document #277.