PATHOGENESIS Porphyria cutanea tarda, the form most commonly associated with ocular surface disease, is sporadic, or it is inherited in an autosomal dominant pattern (band 1p34). The enzyme uroporphyrinogen decarboxylase is deficient, resulting in an accumulation of porphyrins in the liver and in the circulation. Typically, a second insult to the liver such as alcoholism or drug metabolism triggers the condition in late middle age.
A severe form of porphyria, called hepatoerythropoietic porphyria (HEP), is a homozygous presentation of the same enzymatic defect, but onset of the disease is in infancy.
CLINICAL FINDINGS Sun-exposed surfaces develop hyperpigmentation, erythema, scleroderma-like changes, increased fragility, and vesicular and ulcerative lesions. Interpalpebral injection occurs, and the conjunctiva may develop vesicles, necrosis, scarring, and symblepharon mimicking bullous pemphigoid. Necrotizing scleritis has been reported. The cornea may be affected by exposure or by thinning and perforation at the limbus. Skin and ocular lesions may fluoresce.
LABORATORY EVALUATION Urine turns dark on standing. Reduced liver and red cell uroporphyrinogen decarboxylase activity is confirmatory, and hepatic biopsy shows liver parenchyma cells filled with porphyrins that fluoresce bright red in ultraviolet light.
MANAGEMENT Protection from ultraviolet light and reduction of iron by phlebotomy or subcutaneous desferrioxamine are the principal treatments. No specific ocular treatment is available, although artificial tears may help wash away porphyrins. Corneal thinning and perforation are treated in standard ways.
Disorders of Mineral Metabolism
Wilson Disease
Wilson disease (hepatolenticular degeneration) is an autosomal recessive disorder caused by multiple allelic substitutions or deletions in an ATPase, Cu2+-transporting, β-polypeptide linked to chromosome 13q14.3-q21.
PATHOGENESIS Copper is deposited in the liver, then in the kidneys, and eventually in the brain and the cornea at Descemet membrane.
CLINICAL FINDINGS Muscular rigidity increases, and tremor and involuntary movement gradually occur in a fluctuating course resembling parkinsonism. Unintelligible speech and mild dementia usually occur concomitantly. Equal numbers of patients (40%) present with hepatic or nervous system symptoms. In the cornea, a golden brown, ruby red, or green pigment ring (Kayser-Fleischer ring) appears in peripheral Descemet membrane (Fig 11-5), although not all patients with Wilson disease will manifest this ring. Copper deposition occurs in the posterior Descemet membrane, first superiorly, then gradually spreading to meet inferior deposits. Gonioscopy may assist in visualizing the ring. A “sunflower” cataract may be present.
Figure 11-5 Deposits of copper in Descemet membrane in Kayser-Fleischer ring of Wilson hepatolenticular degeneration.
(Reproduced with permission from Krachmer JH, Mannis MJ, Holland EJ, eds. Cornea. 3rd ed. Vol 1. Philadelphia: Elsevier/Mosby; 2011:299.)
The differential diagnosis includes primary biliary cirrhosis, chronic active hepatitis, exogenous chalcosis, and progressive intrahepatic cholestasis of childhood. These and other non-Wilsonian hepatic disorders can also be associated with Kayser-Fleischer rings, but only Wilson disease has decreased serum ceruloplasmin levels and neurologic symptoms.
LABORATORY EVALUATION Patients with Wilson disease can be differentiated from patients with other diseases that show Kayser-Fleischer rings by their inability to incorporate radioactive copper into ceruloplasmin. Low serum ceruloplasmin, high nonceruloplasmin-bound serum copper, and high urinary copper suggest the diagnosis, which can be established with liver biopsy. Nonspecific findings of proteinuria, aminoaciduria, glycosuria, uricaciduria, hyperphosphaturia, and hypercalciuria are seen.
MANAGEMENT Wilson disease can be treated with penicillamine. The Kayser-Fleischer ring disappears gradually with therapy, including liver transplantation, and the disappearance of the rings can be used to help monitor therapy. Electrophysiologic abnormalities from retinal dysfunction have been shown to reverse after disease treatment.
Hypercalcemia
Disorders of calcium and phosphate metabolism are associated with formation of band keratopathy.