Hospital for Sick Children's, The: Atlas of Pediatric Ophthalmology & Strabismus, 1st Edition
Ocular Manifestations of Systemic Disease
Alex V. Levin
Thomas W. Wilson
Vitamins, minerals, and metals are critical for the maintenance of ocular health and are required for the visual process. Many imbalances of these substances can lead to significant vision loss from ocular surface disease, cataract, retinal dysfunction, and optic neuropathies. Vitamin deficiencies can be the result of a decreased intake (starvation, alcoholism, and poor diet) or decreased absorption (cystic fibrosis and inflammatory bowel diseases). Decreased vitamins can also be secondary to abetalipoprotein- emia. Hypervitaminosis can be secondary to consumption of foods high in vitamins (increased vitamin A from ingestion of polar bear liver) or supplemental oral intake. Increased levels of vitamin A have been associated with pseudotumor cerebri and loss of vision secondary to increased intracranial pressure. Decreased levels of vitamin D have been shown to cause corneal band keratopathy.
Poor nutrition is a common cause of vision loss in the third-world countries. Low levels of vitamin B12 and folate can cause significant dysfunction of the optic nerve with irreversible loss of color vision, central vision, and visual field. Vision loss can also occur from low levels of vitamin A. Vitamin A is critical for the functioning of rods and cone photoreceptors.
Supplemental vitamin intake has been recommended for several ocular diseases. For example, supplemental vitamin E, an antioxidant, is commonly administered to premature infants to theoretically decrease free radical oxygen. The effects of vitamin E on retinopathy of prematurity (ROP) have been studied, and the results do not significantly show a harmful or beneficial effect of vitamin E on the severity or progression of ROP.
Figure 22.1 Vitamin A Deficiency—Xerophthalmia
Vitamin A is necessary for growth and proper functioning of epithelium and mucous membranes throughout the body. Deficiency leads to squamous metaplasia, keratinization of mucous-secreting epithelium, thinning of hair, and dry, scaling skin. Ocular changes resulting from vitamin A deficiency are termed xerophthalmia and reflect a conjunctival goblet cell deficiency with potential secondary inflammatory response. Devitalized epithelium will stain with rose Bengal (right image). The World Health Organization's recommendation for the prevention of xerophthalmia in children less than 12 months of age is 100,000 IU vitamin A every 4 to 6 months and for children more than 12 months of age is 200,000 IU vitamin A every 4 to 6 months. In the developed world this is usually achieved through daily dietary intake without supplementation. (The authors are grateful for the contributions of Dr. Christopher Cessna to this legend.)
Figure 22.2 Vitamin A Deficiency
Other signs of hypovitaminosis A include retinal disease, night blindness, decreased rod function mimicking retinitis pigmentosa, and Bitot spots. The latter are keratinized plaques (left image) on the conjunctiva that have a white foamy appearance and tend to be temporal and bilateral. Keratomalacia or melting of the cornea is the most severe form of vitamin A deficiency and is associated with high morbidity/mortality. Fundus specks may be seen in patients with severe vitamin A deficiency. However, the pathophysiology of these lesions is not well understood. Retinal wrinkling of the paramacular area is shown in the right image. Vitamin A deficiency can also exacerbate the ocular and systemic side effects of measles.
Figure 22.3 Vitamin K Deficiency
There are three forms of vitamin K deficiency in children: Early onset, occurring in the first 24 hours of life; classic onset, occurring 1 to 7 days after birth; and late onset, occurring at 2 to 6 weeks old. Patients exhibit coagulopathy due to deficiency of vitamin K–dependent factors II, VII, IX, and X. Early onset is usually due to maternal ingestion of phenobarbital, phenytoin, antituberculosis medications, or anticoagulants. The common classic form is more common in breastfed babies, particularly if they did not receive neonatal supplementation orally or by injection. The late form is more often seen in babies with gastrointestinal malabsorption and/or liver disease, as in this child, who presented in coma due to intracranial bleeding (right image). The classic form of vitamin K deficiency usually presents with gastrointestinal bleeding, intracranial bleeding, large areas of ecchymosis, and umbilical stump hemorrhaging. Retinal hemorrhages are mild and concentrated in the posterior pole (left image). Differential diagnoses would include normal birth and shaken baby syndrome (Chapter 12: Child Abuse). Administration of vitamin K will treat the underlying coagulopathy and confirm the diagnosis.
Figure 22.4 Vitamin B2 Deficiency
Vitamin B2, also known as riboflavin, is present in milk and many vegetables and meats. It is involved with the structure and function of many enzymes, particularly those involved with oxidation reduction. Manifestations of riboflavin deficiency include angular stomatitis and inflammation of the nasal and oral mucosal membranes (left image). Ocular surface disease can be quite symptomatic if not visually threatening (right image, corneal ulcer).
Figure 22.5 Vitamin C Deficiency
Vitamin C, or ascorbic acid, is required in the production of collagen. Deficiency of vitamin C leads to the clinical manifestation known as scurvy. Patients present with irritability, poor appetite, hair loss, petechia due to capillary fragility, gum bleeding, limb tenderness, and pain with movement. Radiographs of the long bones are often diagnostic. Hemorrhaging can occur in the conjunctiva, eyelids, and, less commonly, the orbit and retina. The retinal hemorrhages are few in number and typically confined to the posterior pole. Serum vitamin C levels are an inaccurate reflection of true stores. Lymphocyte assays are required.