Corneal dystrophies are commonly defined as bilateral, symmetric, inherited conditions that appear to have little or no relationship to environmental or systemic factors. Dystrophies begin early in life, are slowly progressive, increase with age, and may not become clinically apparent until years later. They are often characterized by the progressive accumulation of deposits. These deposits result from genetic mutations that lead to transcription of aberrant proteins. Mutations in the transforming growth factor beta–induced gene (TGFBI), which leads to production of the keratoepithelin protein, are an important example.
Many patients with corneal dystrophies associated with deposits present with symptoms of recurrent corneal erosion or blurred vision due to either irregular astigmatism or stromal opacification. This is particularly true when the pathology is more superficial, encroaching on the epithelial basement membrane complex. However, there are patients who experience blurred vision because of corneal edema (eg, as in Fuchs endothelial corneal dystrophy) or because of dystrophies not associated with deposits (eg, epithelial basement membrane dystrophy); the latter example may in fact be a degeneration rather than a dystrophy. In general, these conditions are in the process of redefinition and recharacterization.
To more accurately reflect the evolving genetic, clinical, and histologic characteristics of the dystrophies, the International Committee for the Classification of Corneal Dystrophies (IC3D) revised the dystrophy nomenclature. In this reclassification, updated in 2015, each dystrophy is classified into 1 of 4 groups: epithelial and subepithelial dystrophies, epithelial–stromal TGFBI dystrophies, stromal dystrophies, and endothelial dystrophies. The dystrophies are described according to a template consisting of clinical, pathologic, and genetic information. The system is upgradable and can be retrieved at www.corneasociety.org.
In addition, the strength of evidence for each dystrophy is described using 1 of 4 assigned categories (Table 7-1). The category assignment may change as more information about an individual dystrophy is obtained. It is hoped that, over time, all valid corneal dystrophies will attain category 1 status. The IC3D classification of major corneal dystrophies is summarized in Table 7-2. A fairly comprehensive treatment of all corneal dystrophies is available in the IC3D publication and is beyond the scope of the BCSC. This chapter provides a basic discussion of the more common dystrophies for which there is the best evidence.
The genetics of major corneal dystrophies is summarized in Table 7-3. Although learning the genetics of each dystrophy is not critical to developing a basic understanding of these diseases, it is important to appreciate the significance of particular genetic mutations. For example, mutations in the TGFBI gene lead to most of the stromal corneal dystrophies associated with recurrent corneal erosions. In addition, there are dystrophies that appear the same phenotypically but differ genetically; conversely, dystrophies due to mutations in the same gene may have different phenotypes.
During the clinical examination, the ophthalmologist is encouraged to consider the following questions to determine whether a dystrophy is present and to differentiate between the corneal dystrophies:
Are other family members affected?
Are there signs of inflammation (eg, stromal cells or neovascularization)? If so, the condition may not be a dystrophy.
Are the corneal opacities present in both eyes and, if so, are they symmetric or asymmetric?
In which corneal layer(s) do the opacities appear?
Are there clear zones between the lesions?
Do the lesions extend to the limbus?
Is the cornea abnormally thick, thin, or of normal thickness?
Is the morphology of the lesions suggestive of a corneal dystrophy?
Table 7-1 The IC3D Categories of Evidence for the Corneal Dystrophies
Table 7-2 Major Corneal Dystrophies in the IC3D Classification
Obtaining a family history is essential. Examination of biological relatives who have accompanied the patient to the office may be revealing, and genetic testing of the patient or affected family members may also be helpful.
For further discussion of genetics, see the genetics section in BCSC Section 2, Fundamentals and Principles of Ophthalmology. See also Section 4, Ophthalmic Pathology and Intraocular Tumors, Chapter 6.
Weiss JS, Møller HU, Aldave AJ, et al. IC3D classification of corneal dystrophies—edition 2. Cornea. 2015;34(2):117–159.
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.