Metabolic Disorders Affecting the Cornea or Iris
See also Chapter 28, Ocular Manifestations of Systemic Disease, and Table 28-2.
The mucopolysaccharidoses (MPSs) are a group of lysosomal storage diseases. Ocular manifestations can include corneal haze from incompletely degraded glycosaminoglycan. Corneal haze may be present in early life in MPS IH (Hurler syndrome), MPS IS (Scheie syndrome), and MPS IV (Morquio syndrome). Treatment options for significant opacities include penetrating keratoplasty and DALK. Enzyme replacement therapy is available for certain forms of these lysosomal storage diseases. See BCSC Section 8, External Disease and Cornea, for further discussion.
Cystinosis is caused by biallelic CTNS mutations. The infantile form includes failure to thrive, rickets, and progressive renal failure, resulting in Fanconi syndrome.
Iridescent, elongated corneal crystals appear at approximately age 1 year, first in the peripheral cornea and the anterior stroma. Crystals also present in the uvea and on the surface of the iris. Corneal crystals result in severe photophobia. There are reports of angle-closure glaucoma secondary to crystal deposition in the ciliary body.
Oral cysteamine alleviates systemic problems but not the corneal crystal deposition. Topical cysteamine can reduce corneal crystal deposition but requires frequent application, may be difficult to obtain, and has an unpleasant odor.
Tyrosinemia type II
Tyrosinemia type II (Richner-Hanhart syndrome) results from biallelic TAT mutations and is associated with photophobia, pseudodendritic ulcers on the cornea, and ulceration on the palms and soles. Systemic problems include liver and kidney dysfunction. Dietary restriction of phenylalanine and tyrosine is the mainstay of treatment.
In Wilson disease (hepatolenticular degeneration), there is excess copper deposition in the liver, kidneys, and basal ganglia of the brain, leading to cirrhosis, renal tubular damage, and a Parkinson-like disorder of motor function. The phenotype results from biallelic ATP7B mutations. The characteristic Kayser-Fleischer ring—a golden-brown, ruby-red, or green pigment ring consisting of copper deposits—is limited to Descemet membrane, can be several millimeters in width, and may resolve with treatment. Laboratory tests for serum copper and ceruloplasmin are better than an eye examination for early diagnosis because the ring can develop late.
Fabry disease is an X-linked lysosomal storage disease with variable systemic manifestations. It is due to α-galactosidase deficiency (hemizygous GLA mutations). Vortex keratopathy (verticillata) can be seen in affected males and in female carriers.
Schnyder corneal dystrophy
Schnyder corneal dystrophy is a predominantly local disorder of corneal lipid metabolism arising from biallelic UBIAD1 mutations. Although crystalline keratopathy is characteristic, stromal haze without crystals is a common presentation.
Excerpted from BCSC 2020-2021 series: Section 10 - Glaucoma. For more information and to purchase the entire series, please visit https://www.aao.org/bcsc.