Background
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 crystalline corneal dystrophy (SCCD) specific to age.
View Image | 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 SCCD) 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 SCCD.
The recent discovery of the causative gene, UBIAD1, 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 33 families over a period of 18 years reveals that most morbidity derives from progressive corneal clouding, leading to glare and decreased vision in daylight.
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. Nevertheless, while scotopic vision remained relatively good, increasing corneal opacification with age resulted in decreased scotopic vision.
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 SCCD. 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
SCCD can occur in whites, Asians, and African Americans.
Sex
Although rare sporadic cases have been reported, SCCD 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.
History
The dystrophy can appear as early as the first year of life. Progression is slow. See the following image.
View Image | 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, SCCD 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. Patients possess excellent visual acuity and normal corneal sensation.
View Image | A 22-year-old woman with circular corneal opacity best seen in retroillumination. Weiss JS: Schnyder's dystrophy of the cornea: a Swede-Finn connectio.... |
Patients aged 23-39 years develop arcus lipoides as shown below. Snellen acuity may be diminished if measured under daylight conditions. Corneal sensation begins to decrease.
View Image | A 37-year-old man with central disclike opacity, affecting the entire stromal thickness, anterior stromal cholesterol crystals, and peripheral arcus l.... |
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.
View Image | 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 corn.... |
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.
Laboratory Studies
Both affected and unaffected members of SCCD pedigrees may have hyperlipidemia and/or hypercholesterolemia.
Other Tests
Confocal microscopy in more advanced stages of SCCD 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 SCCD (see the image below) resembles deposition of cholesterol crystals in human atherosclerotic lesions.
View Image | A 20-year-old woman with ringlike deposition of anterior stromal cholesterol crystals. Weiss JS: Schnyder's dystrophy of the cornea: a Swede-Finn conn.... |
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.
Penetrating keratoplasty can be performed successfully in those patients with advanced disease, but dystrophy can recur in the graft.
Phototherapeutic keratectomy can remove subepithelial crystals if they are causing decreased vision and glare.
Further Outpatient Care
Patients should receive follow-up care as needed.
Prognosis
Results of clinical examination have shown that crystalline deposits are present in only 51% of patients with SCCD.
Some patients have been documented to have unilateral crystalline deposition. Therefore, the crystalline aspect of SCCD is a continuum; some people manifest crystals bilaterally, some unilaterally, and others not at all.
While SCCD may be diagnosed easily during the first decade of life, the diagnosis of patients with SCCD sine crystals is more challenging and is reported to be delayed up to the fourth decade. Why the corneal cholesterol forms crystals in some patients, but not in others, remains unclear.
Contrary to prior reports, many patients with SCCD 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).
Author
Jayne S Weiss, MD, Professor of Ophthalmology, Director of Refractive Surgery, Kresge Eye Institute, Wayne State University School of Medicine
Disclosure: Nothing to disclose.
Coauthor(s)
Brad Spagnolo, MD,
Disclosure: Nothing to disclose.
Specialty Editors
Simon K Law, MD, PharmD, Clinical Professor of Health Sciences, Department of Ophthalmology, Jules Stein Eye Institute, University of California, Los Angeles, David Geffen School of Medicine
Disclosure: Nothing to disclose.
Christopher J Rapuano, MD, Professor, Department of Ophthalmology, Sidney Kimmel Medical College of Thomas Jefferson University; Director of the Cornea Service, Co-Director of Refractive Surgery Department, Wills Eye Hospital
Disclosure: Serve(d) as a director, officer, partner, employee, advisor, consultant or trustee for: Cornea Society, AAO, OMIC, Avedro; Bio-Tissue; GSK, Kala, Novartis; Shire; Sun Ophthalmics; TearLab<br/>Serve(d) as a speaker or a member of a speakers bureau for: Avedro; Bio-Tissue; Shire<br/>Received income in an amount equal to or greater than $250 from: AAO, OMIC, Avedro; Bio-Tissue; GSK, Kala, Novartis; Shire; Sun Ophthalmics; TearLab.
Chief Editor
Hampton Roy, Sr, MD, Associate Clinical Professor, Department of Ophthalmology, University of Arkansas for Medical Sciences
Disclosure: Nothing to disclose.
Additional Contributors
Fernando H Murillo-Lopez, MD, Senior Surgeon, Unidad Privada de Oftalmologia CEMES
Disclosure: Nothing to disclose.
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