Hospital for Sick Children's, The: Atlas of Pediatric Ophthalmology & Strabismus, 1st Edition

Ocular Manifestations of Systemic Disease



Alex V. Levin

Thomas W. Wilson

Stephen P

During development, neural crest migration to form the gastrointestinal tract and many of the ocular tissues occurs at similar times of gestation. As a result, some abnormalities of both systems may coexist. Yet, other coexisting abnormalities seem to have their basis in manifestations of a mutated gene that has a role in both locations that may be quite different and not embryologically based. Some gastrointestinal disorders also involve the eye as a complication of the primary problem, as seen with iron deposition in Wilson disease. Gastrointestinal disorders, such as Alagille syndrome, may be indications for eye examination both for diagnosis and for possible later complications. Some ocular findings, such as uveitis, should prompt the ophthalmologist to consider gastrointestinal manifestations that have yet to be recognized or diagnosed, such as inflammatory bowel disease.



Figure 17.1 Inflammatory Bowel Disease—Episcleritis

Inflammatory bowel disease is a term encompassing ulcerative colitis, Crohn disease, and overlap patients. It is a chronic gastrointestinal disorder with potential ophthalmic manifestations both related to the disease and secondary to its treatment. Patients can develop diffuse (seen in this image) or nodular episcleritis, and there may be a correlation with gastrointestinal disease activity. There may be associated mild nongranulomatous iritis. The episcleritis often responds to systemic treatment of the gastrointestinal disease, but topical treatment is useful, particularly when patients have pain and uveitis.


Figure 17.2 Inflammatory Bowel Disease—Scleritis

Nodular and posterior scleritis are uncommon findings of inflammatory bowel disease. Nodular scleritis is more common in Crohn disease than ulcerative colitis and more severe when there is also arthritis involving large peripheral joints. Posterior scleritis causes severe pain and potential vision loss from optic nerve or retinal edema. The retinal folds and peripapillary elevation seen in this photograph are secondary to the severe scleral inflammation and thickening, mimicking a posterior retrobulbar mass. The sclera is thickened on B-scan ultrasound.


Figure 17.3 Inflammatory Bowel Disease—Chorioretinitis

The white patches and areas of pigmentation seen in this image are the result of chorioretinitis and subsequent retinal pigment epithelium hypertrophy, respectively. Macular involvement can reduce the visual acuity. Papillitis (Chapter 9: Optic Nerve, Fig. 9.27) and retinal vasculitis are other uncommon manifestations of inflammatory bowel disease. Retinal vasculitis and chorioretinitis can coexist. Systemic treatment of the gastrointestinal disease with consideration of sub-Tenon deposteroids is recommended for the fundus manifestations of inflammatory bowel disease.




Figure 17.4 Hirschsprung Disease

Hirschsprung disease, or congenital megacolon, is a common cause of neonatal bowel obstruction in infants. The underlying cause is failure of embryonic neural crest migration into the muscular layers of the colon. Likewise, failure for the neural crest derived melanocytes of the iris to reach their target destination results in sector iris heterochromia (Chapter 6, Iris and Pupils, Fig. 6.21). Patients present with failure to thrive and chronic constipation. This photograph shows a barium enema revealing the characteristic finding of severe dilation of the colon with areas of constriction. The areas of glomal innervation are dilated and the areas of constriction are aganglionic. The diagnosis can be confirmed with anorectal manometry, which shows an increased pressure in patients with congenital megacolon. Rectal biopsy reveals a lack of ganglion cells in the submucosal and intramuscular layers. Treatment is surgical and includes resection of the aganglionic colon with colostomy of the distal portion of the normally innervated colon.


Figure 17.5 Icterus

Icterus is the result of high serum bilirubin levels and coincides with jaundice. Bilirubin, especially when unconjugated, has a high affinity for elastin, which is concentrated in the episclera and conjunctiva. The common term scleral icterus is therefore a misnomer. High levels of bilirubin are the result of excessive production or decreased secretion and can cause brain damage. Elevated bilirubin is often seen in neonates, especially premature infants and newborns with hemolysis secondary to Rh incompatibility. Hepatitis or other bile duct abnormalities can also elevate serum bilirubin levels.


Figure 17.6 Wilson Disease—Kayser-Fleischer Ring

Wilson disease, also known as hepatolenticular degeneration, is an autosomal recessive disorder of copper metabolism resulting in tissue deposition of copper. Levels of ceruloplasmin, the copper-transporting protein, are low. Unbound freely circulating copper is then deposited into numerous tissues including the liver, brain, kidneys, and cornea. Deposition of copper in the peripheral Descemet membrane forms a ring of golden brown or aqua-colored deposits called a Kayser-Fleischer ring. The deposits usually start superior-temporally and are most concentrated at the 12 and 6 o'clock positions. Recognition can be difficult in the presence of icterus (Fig. 17.5), and some recommend gonioscopy for diagnosis.




Figure 17.7 Wilson Disease— Sunflower Cataract

Copper deposition may also occur in the lens capsule, leading to a “sunflower” pattern. This finding is usually visually insignificant and does not require surgery, but without treatment of the systemic disorder visual loss can occur. Treatment in Wilson disease is based on the need to remove excess copper through chelation and limit dietary intake and absorption of copper. (Note: The multiple white dots around the light reflex in this image are artifact.)


Figure 17.8 Alagille Syndrome— Retinopathy

Alagille syndrome is an autosomal dominant disorder characterized by biliary atresia (intrahepatic cholestasis), cardiovascular abnormalities including moyamoya abnormality in the brain, mental retardation in approximately 15%, and butterfly-shaped vertebra. The characteristic facial features include a pointed chin, deep-set eyes, telecanthus, and a bulbous nose. Typical retinal pigmentary changes are seen in one third of patients, as demonstrated here in a child who is also myopic. They may even be present in infancy. Chorioretinal atrophy is seen later in the disease course.


Figure 17.9 Alagille Syndrome— Posterior Embryotoxon

An anterior displaced Schwalbe line (white line at arrows), also known as posterior embryotoxon, is seen in over two thirds of patients with Alagille syndrome. However, it is also present in 10% of the normal population and in other disorders such as Axenfeld-Rieger syndrome (Chapter 6: Iris and Pupils, Fig. 6.15). Unlike Axenfeld-Rieger, posterior embryotoxon in Alagille syndrome is not associated with glaucoma. Gonioscopy may be helpful in identifying this malformation.