Schnyder Corneal Dystrophy 

Updated: Jun 10, 2020
Author: Ahmed Farghaly Abdelhameed Omar, MD, PhD; Chief Editor: Hampton Roy, Sr, MD 

Overview

Background

Schnyder corneal dystrophy (SCD), also called Schnyder crystalline corneal dystrophy (SCCD), is a rare autosomal-dominant stromal dystrophy that is characterized by bilateral corneal opacification, resulting from an abnormal accumulation of cholesterol and lipid. The causative gene for this disease is UBIAD1, which is present on 1p36. The gene is involved in cholesterol metabolism.

Please refer to the image below depicting the natural history of Schnyder corneal dystrophy specific to age.

The natural history of Schnyder dystrophy with age The natural history of Schnyder dystrophy with age. Weiss JS: Schnyder's dystrophy of the cornea: a Swede-Finn connection. Cornea 1992; 11(2): 93-101.

Van Went and Wibaut first described crystalline dystrophy in the Dutch literature in 1924, and it was delineated further by Schnyder in the Swiss literature in 1929.[1, 2]

While the incidence in the general population is unknown, the world's largest pedigree (>200 patients with Schnyder corneal dystrophy) has a Swede-Finn heritage and has been traced to the southwest coast of Finland on the Bay of Bothnia. However, the dystrophy has been reported in other ethnicities and in all racial groups.

Pathophysiology

The pathogenesis remains unknown, but it is postulated to result from a localized defect of lipid metabolism. It has been demonstrated in affected corneas versus normal corneas that the cholesterol content increases 10-fold and the phospholipid content increases 5-fold. Immunohistochemical analysis has revealed the preferential deposition of apolipoprotein components of high-density lipoprotein (HDL), that is, apoA I, apoA II, and apoC, but not of low-density lipoprotein (LDL), that is, apoB. This finding suggests an abnormal metabolism of HDL in the cornea with Schnyder corneal dystrophy.

The discovery of the causative gene, UBIAD1 (UbiA prenyltransferase domain-containing protein-1), will be the link to further understanding of this disease. The gene produces a protein that contains a prenyltransferase domain that could play a role in cholesterol metabolism. In addition, UBIAD1 interacts with the C-terminal portion of apolipoprotein E (apoE), which is known to help mediate cholesterol removal from the cells. Further research will determine whether the excess cholesterol results from increased cholesterol production or decreased removal.

Epidemiology

Frequency

United States

The dystrophy has been reported in the United States, although the incidence in the general population is unknown.

International

While the incidence is unknown, the dystrophy has been reported in eastern and western Europe, Taiwan, Japan, and Turkey.

Mortality/Morbidity

A long-term study of 34 families over a period of 18 years revealed that most morbidity derives from progressive corneal clouding, leading to glare and decreased vision in daylight.[3]

In this study, mean Snellen uncorrected visual acuity (UCVA) was between 20/25 and 20/30 in patients younger than 40 years and between 20/30 and 20/40 in patients aged 40 years or older. Scotopic vision remained relatively good until later in life, when corneal opacification increased.

Studies of those affected reveal that 54% of patients aged 50 years and older and 77% of patients aged 70 years and older had corneal transplant surgery. Although study numbers are small, there is no evidence of increased mortality from cardiovascular disease in Schnyder corneal dystrophy. Of note, however, 71% of patients who had corneal transplant surgery reported the use of cholesterol-lowering agents. This was not statistically different from those patients who had not undergone corneal transplant surgery.

Race

Schnyder corneal dystrophy can occur in whites, Asians, and African Americans.

Sex

Although rare sporadic cases have been reported, Schnyder corneal dystrophy is primarily an autosomal dominant disease, affecting both sexes with equal probability.

Age

The disease may appear as early as the first decade of life and slowly progresses with age. However, a diagnosis may be delayed until the fourth decade in patients with corneal opacification without crystalline deposits.

Prognosis

Results of clinical examination have shown that crystalline deposits are present in only 51% of patients with Schnyder corneal dystrophy.[4]

While Schnyder corneal dystrophy may be diagnosed easily during the first decade of life, the diagnosis Schnyder corneal dystrophy sine crystals is more challenging and is reported to be delayed up to the fourth decade of life. Some patients have been documented to have unilateral crystalline deposition. Why the corneal cholesterol forms crystals in some patients, but not in others, remains unclear.

Contrary to prior reports, many patients with Schnyder corneal dystrophy eventually require corneal transplantation because of glare and decreased vision in daylight.

Patient Education

For excellent patient education resources, visit eMedicineHealth's Cholesterol Center. Also, see eMedicineHealth's patient education articles High Cholesterol, Cholesterol FAQs, and Atorvastatin (Lipitor).

 

Presentation

History

The dystrophy can appear as early as the first year of life. Progression is slow. See the following image.

The natural history of Schnyder dystrophy with age The natural history of Schnyder dystrophy with age. Weiss JS: Schnyder's dystrophy of the cornea: a Swede-Finn connection. Cornea 1992; 11(2): 93-101.

Physical

Typically, Schnyder corneal dystrophy can be diagnosed clinically. The diagnosis may be more difficult in patients without crystals.

The corneal findings are predictable on the basis of the patient's age. Loss of corneal sensation may be more profound in advanced cases.

Patients who are younger than 23 years demonstrate only a central corneal opacity (as depicted below), which may involve the entire stroma with or without central subepithelial cholesterol crystals. Central corneal mosaic opacities have been reported. These patients possess excellent visual acuity and normal corneal sensation.

A 22-year-old woman with circular corneal opacity A 22-year-old woman with circular corneal opacity best seen in retroillumination. Weiss JS: Schnyder's dystrophy of the cornea: a Swede-Finn connection. Cornea 1992; 11(2): 93-101.

Patients aged 23-39 years develop arcus lipoides as shown below. Snellen acuity may be diminished if measured under photopic conditions. Corneal sensation begins to decrease.

A 37-year-old man with central disclike opacity, a A 37-year-old man with central disclike opacity, affecting the entire stromal thickness, anterior stromal cholesterol crystals, and peripheral arcus lipoides. Weiss JS: Schnyder's dystrophy of the cornea: a Swede-Finn connection. Cornea 1992; 11(2): 93-101.

In patients older than 39 years, a midperipheral, panstromal corneal haze appears that fills in the area between the central opacity and the peripheral arcus.

Often, the arcus is dense enough to be seen without a slit lamp as depicted below.

A 78-year-old woman with dense arcus lipoides in t A 78-year-old woman with dense arcus lipoides in the corneal periphery, sparing the corneal scleral limbus. Weiss JS: Schnyder's dystrophy of the cornea: a Swede-Finn connection. Cornea 1992; 11(2): 93-101.

These patients usually demonstrate an objective loss of visual acuity (which appears worse under photopic conditions) and reduced corneal sensation.

In some members of families with this dystrophy, the presence of xanthelasma associated with elevated levels of serum cholesterol, triglycerides, and lipoproteins has been described.

While scotopic visual acuity may be good, a more accurate assessment of visual function can be obtained by measuring visual acuity under photopic conditions.

Causes

See Pathophysiology.

 

DDx

Diagnostic Considerations

Systemic abnormalities affecting lipid metabolism and resulting in central corneal clouding include the following: fish eye disease, lecithin-cholesterol acyltransferase (LCAT) deficiency, and Tangier disease.[5]

Diseases with corneal crystals include the following: cystinosis, dysproteinemias, hyperuricemia, multiple myeloma, porphyria, and primary or secondary lipid keratopathy.

Differential Diagnoses

 

Workup

Laboratory Studies

It is prudent to obtain fasting serum lipid levels, as both affected and unaffected members of Schnyder corneal dystrophy pedigrees may have hyperlipidemia and/or hypercholesterolemia.

Other Tests

Confocal microscopy in more advanced stages of Schnyder corneal dystrophy may reveal the absence of corneal nerves.

Genetic testing should reveal mutations in the UBIAD1 gene in affected individuals.

Histologic Findings

Histopathology shows unesterified and esterified cholesterol in basal epithelium; Bowman layer; stroma; and, occasionally, endothelium. Electron microscopy reveals dissolved lipid particles scattered in the subepithelial space throughout the stroma and, rarely, the endothelium. Immunohistochemical analysis has revealed the preferential deposition of apolipoprotein components of HDL. Deposition of cholesterol crystals in patients with Schnyder corneal dystrophy (see the image below) resembles deposition of cholesterol crystals in human atherosclerotic lesions.

A 20-year-old woman with ringlike deposition of an A 20-year-old woman with ringlike deposition of anterior stromal cholesterol crystals. Weiss JS: Schnyder's dystrophy of the cornea: a Swede-Finn connection. Cornea 1992; 11(2): 93-101.
 

Treatment

Medical Care

No local or systemic medical treatment is available to stop the progression of corneal lipid deposition or the alteration of serum cholesterol levels.

Surgical Care

Penetrating keratoplasty (PKP) can be performed successfully in those patients with advanced disease, but the dystrophy can recur in the graft. One study showed recurrence in 21% of eyes who underwent PKP.[3]

Phototherapeutic keratectomy can remove subepithelial crystals if they are causing decreased vision and glare, but it does not reduce panstromal haze.[6]

Long-Term Monitoring

Patients should receive follow-up care as needed.