eMedicine Specialties > Ophthalmology > Cornea

Dystrophy, Crystalline

Jayne S Weiss, MD, Professor of Ophthalmology, Director of Refractive Surgery, Kresge Eye Institute, Wayne State University
Brad Spagnolo, MD, Ophthalmology, Baltimore-Washington Eye Center

Updated: Jul 11, 2008

Introduction

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.

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.

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.

Clinical

History

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

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

Differential Diagnoses

Dystrophy, Granular
Dystrophy, Lattice
Dystrophy, Macular
Hyperlipoproteinemia

Workup

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 resembles deposition of cholesterol crystals in human atherosclerotic lesions.

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.
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.

Follow-up

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 eMedicine's Cholesterol Center and Statins Center. Also, see eMedicine's patient education articles High Cholesterol, Cholesterol FAQs, and Atorvastatin (Lipitor).

Miscellaneous

Medicolegal Pitfalls

Given the increased risk of hyperlipidemia in patients with SCCD and their relatives, making the correct diagnosis, referring the patient for a medical examination, and providing appropriate treatment (if necessary) are important.

Multimedia

Media file 1: 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.

Media file 2: 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.

Media file 3: 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.

Media file 4: 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.

Media file 5: 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.

References

Van Went JM, Wibaut F. Een zyeldzame erfelijke hoornvliesaandoening. Ned Tijdschr Geneeskd. 1924;68(B):2996-2997.
Schnyder WF. Mitteilung uber einen neuen Typus von familiarer hornhauterkrankung. Schweiz Med Wochenschr. 1929;59:559-571.
Bron AJ. Corneal changes in the dislipoproteinaemias. Cornea. 1989;8(2):135-40. [Medline].
Bron AJ, Williams HP, Carruthers ME. Hereditary crystalline stromal dystrophy of Schnyder. I. Clinical features of a family with hyperlipoproteinaemia. Br J Ophthalmol. May 1972;56(5):383-99. [Medline].
Delleman JW, Winkelman JE. Degeneratio corneae cristallinea hereditaria. A clinical, genetical and histological study. Ophthalmologica. 1968;155(5):409-26. [Medline].
Freddo TF, Polack FM, Leibowitz HM. Ultrastructural changes in the posterior layers of the cornea in Schnyder's crystalline dystrophy. Cornea. Sep 1989;8(3):170-7. [Medline].
Gaynor PM, Zhang WY, Weiss JS, et al. Accumulation of HDL apolipoproteins accompanies abnormal cholesterol accumulation in Schnyder's corneal dystrophy. Arterioscler Thromb Vasc Biol. Aug 1996;16(8):992-9. [Medline].
Gibbels E, Schaefer HE, Runee U, et al. Severe polyneuropathy in Tangier disease mimicking syringomyelia or leprosy. Clinical, biochemical, electrophysiological, and morphological evaluation, including electron microscopy of nerve, muscle, and skin biopsies. J Neurology. 1985;232(5):283-294. [Medline].
Gjone E. Familial lecithin cholesterol acyltransferase (LCAT) deficiency. Birth Defects Orig Artic Ser. 1982;18(6):423-31. [Medline].
Hoang-Xuan T, Pouliquen Y, Gasteau J. [Schnyder's crystalline dystrophy. II. Association with genu valgum]. J Fr Ophtalmol. 1985;8(11):743-7. [Medline].
McCarthy M, Innis S, Dubord P, et al. Panstromal Schnyder corneal dystrophy. A clinical pathologic report with quantitative analysis of corneal lipid composition. Ophthalmology. May 1994;101(5):895-901. [Medline].
Orr A, Dube MP, Marcadier J, et al. Mutations in the UBIAD1 gene, encoding a potential prenyltransferase, are causal for Schnyder crystalline corneal dystrophy. PLoS ONE. Aug 1 2007;2(1):e685. [Medline].
Philipson BT. Fish eye disease. Birth Defects Orig Artic Ser. 1982;18(6):441-8. [Medline].
Rodrigues MM, Kruth HS, Krachmer JH, et al. Unesterified cholesterol in Schnyder's corneal crystalline dystrophy. Am J Ophthalmol. Aug 15 1987;104(2):157-63. [Medline].
Theendakara V, Tromp G, Kuivaniemi H, et al. Fine mapping of the Schnyder's crystalline corneal dystrophy locus. Hum Genet. May 2004;114(6):594-600. [Medline].
Vesaluoma MH, Linna TU, Sankila EM, et al. In vivo confocal microscopy of a family with Schnyder crystalline corneal dystrophy. Ophthalmology. May 1999;106(5):944-51. [Medline].
Weiss JS. Schnyder crystalline dystrophy sine crystals. Recommendation for a revision of nomenclature. Ophthalmology. Mar 1996;103(3):465-73. [Medline].
Weiss JS. Schnyder's dystrophy of the cornea: a Swede-Finn connection. Cornea. Mar 1992;11(2):93-101. [Medline].
Weiss JS. Visual morbidity in thirty three families with Schnyder's crystalline corneal dystrophy. Transactions of the American Ophthalmology Society. In press.
Weiss JS, Kruth HS, Kuivaniemi H, et al. Mutations in the UBIAD1 gene on chromosome short arm 1, region 36, cause Schnyder crystalline corneal dystrophy. Invest Ophthalmol Vis Sci. Nov 2007;48(11):5007-12. [Medline].
Weiss JS, Rodrigues MM, Kruth HS, et al. Panstromal Schnyder's corneal dystrophy. Ultrastructural and histochemical studies. Ophthalmology. Jul 1992;99(7):1072-81. [Medline].
Weller RO, Rodger FC. Crystalline stromal dystrophy: histochemistry and ultrastructure of the cornea. Br J Ophthalmol. Jan 1980;64(1):46-52. [Medline].
Wu CW, Lin PY, Liu YF, et al. Central corneal mosaic opacities in Schnyder's crystalline dystrophy. Ophthalmology. Apr 2005;112(4):650-3. [Medline].

Keywords

crystalline dystrophy, Schnyder's crystalline corneal dystrophy, SCCD, Schnyder corneal dystrophy, SCD, hereditary crystalline stromal dystrophy of Schnyder, corneal crystalline dystrophy of Schnyder, crystalline stromal dystrophy, central stromal crystalline corneal dystrophy, Schnyder crystalline dystrophy sine crystals

Contributor Information and Disclosures

Author

Jayne S Weiss, MD, Professor of Ophthalmology, Director of Refractive Surgery, Kresge Eye Institute, Wayne State University
Jayne S Weiss, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Ophthalmology, American Ophthalmological Society, Association for Research in Vision and Ophthalmology, Eye Bank Association of America, and Phi Beta Kappa
Disclosure: Nothing to disclose.

Coauthor(s)

Brad Spagnolo, MD, Ophthalmology, Baltimore-Washington Eye Center
Brad Spagnolo, MD is a member of the following medical societies: American Academy of Ophthalmology and American Society of Cataract and Refractive Surgery
Disclosure: Nothing to disclose.

Medical Editor

Fernando H Murillo-Lopez, MD, Senior Surgeon, Unidad Privada de Oftalmologia CEMES
Fernando H Murillo-Lopez, MD is a member of the following medical societies: American Academy of Ophthalmology
Disclosure: Nothing to disclose.

Pharmacy Editor

Simon K Law, MD, PharmD, Assistant Professor of Ophthalmology, Jules Stein Eye Institute; Chief of Section of Ophthalmology Surgical Services, Department of Veterans Affairs Healthcare Center, West Los Angeles
Simon K Law, MD, PharmD is a member of the following medical societies: American Academy of Ophthalmology, American Glaucoma Society, and Association for Research in Vision and Ophthalmology
Disclosure: Nothing to disclose.

Managing Editor

Christopher J Rapuano, MD, Professor, Department of Ophthalmology, Jefferson Medical College of Thomas Jefferson University; Co-Chairman of the Cornea Service, Co-Chairman of Refractive Surgery Department, Wills Eye Institute
Christopher J Rapuano, MD is a member of the following medical societies: American Academy of Ophthalmology, American Society of Cataract and Refractive Surgery, Eye Bank Association of America, Pennsylvania Medical Society, and Philadelphia County Medical Society
Disclosure: Allergan Honoraria Speaking and teaching; Allergan Consulting fee Consulting; Alcon Honoraria Speaking and teaching; Inspire Honoraria Speaking and teaching; RPS Ownership interest Other

CME Editor

Lance L Brown, OD, MD, Ophthalmologist, Affiliated With Freeman Hospital and St John's Hospital, Regional Eye Center, Joplin, Missouri
Disclosure: Nothing to disclose.

Chief Editor

Hampton Roy Sr, MD, Associate Clinical Professor, Department of Ophthalmology, University of Arkansas for Medical Sciences
Hampton Roy Sr, MD is a member of the following medical societies: American Academy of Ophthalmology, American College of Surgeons, and Pan-American Association of Ophthalmology
Disclosure: Nothing to disclose.

Further Reading