Corneal stromal dystrophy (CSD) includes a number of disorders such as macular, granular, reticular, lattice, fleck, and congenital stroma dystrophies [1]. It is a genetic disease, and its incidence varies between different regions [2] [3]. The inheritance pattern of CSD is mostly autosomal dominant, although other patterns such as recessive or X-linked have been described. Mutations in any one of several genes, such as transforming growth factor beta-induced (TGFBI), carbohydrate sulfotransferase 6 (CHST6), or keratin 3 (KRT3), lead to particular forms of CSD [4] [5]. The extent of the phenotypic expression of a mutation varies between individuals. Corneal dystrophies, in general, involve disease of the cornea, while CSD specifically affects the stroma.

CSD is characterized by corneal opacities that are often bilateral and symmetrical. These lesions are caused by the deposition of non-transparent matter, which is not preceded by a history of inflammation or trauma to the eye. The deposited material may be present as ill-defined or irregular sheet, line, ring, dot or flake shaped areas. The surrounding cornea may be clear or opacified as well.

The features of CSD are variable with regard to the degree of visual impairment, presence or absence of systemic symptoms, and the severity of symptoms. CSD is usually slowly progressive. It may manifest congenitally (for example in congenital stroma corneal dystrophy), or as late as the fourth decade of life (for example in lattice corneal dystrophy type II), although its onset is commonly during childhood (examples are macular, fleck and granular corneal dystrophy) [6]. Visual impairment is manifested as mild to severely decreased visual acuity, due to the altered corneal composition as well as reduced focusing power, although some patients such as those with fleck corneal dystrophy (FCD) suffer no loss of acuity throughout the course of the disease.

• Myopathy

  […] dysplasia congenita Spondyloepimetaphyseal dysplasia, Strudwick type Kniest dysplasia (see also C2/11 ) COL3 : Ehlers–Danlos syndrome, types 3 & 4 Sack–Barabas syndrome COL4 : Alport syndrome COL5 : Ehlers–Danlos syndrome, types 1 & 2 COL6 : Bethlem myopathy [en.wikipedia.org]

• Corneal Edema

  Most patients remain asymptomatic and corneal edema is usually absent. [en.wikipedia.org]

  Further electron microscopic study of hereditary corneal edema. Invest Ophthalmol 1971;10:545-54. 11. Kanai A, Waltman S, Polack FM, Kaufman HE. Electron microscopic study of hereditary corneal edema. Invest Ophthalmol 1971;10:89-99. 12. [reviewofophthalmology.com]

  Foulks GN: Treatment of recurrent corneal erosions and corneal edema with topical osmotic colloidal solution. Ophthalmology 88:801, 1981 21. [oculist.net]

  Congenital hereditary corneal edema of Maumenee: its clinical fetures, management, and pathology. Br J Opthalmol. 1987; 71:130-44. 80. Schid E, Lisch W, Philipp W, et al. A new, X-linked endothelial corneal dystrophy. [reviewofcontactlenses.com]

• Protruding Lips

  lips, skin laxity, "hound dog" ) cranial and peripheral neuropathy -cardiac and renal failure -lattice may look like prominent corneal nerves (nerves won't show up in retroillumination ) -manifests later in life than L1 Lattice 3 and 3A Dystrophy -stromal [studyblue.com]

  lips and pendulous ears (due to amyloid deposition and secondary muscular dysfunction) Pathology Sub-Bowman layer deposits of amyloid lattice lines and intra-lamellar amyloid deposits, most prominent at the limbus. [eyewiki.aao.org]

  It presents in early adulthood with peripheral neuropathies, cranial neuropathies, hound-like facies, dry skin, blepharochalasis, protruding lips, and corneal lattice lines. [webeye.ophth.uiowa.edu]

Diagnosis is usually clinical, and combines the patient's history, such as age of onset and family history of corneal stromal dystrophy, with the observation of abnormal deposits on the cornea by a slit lamp examination. This is reinforced by molecular and biochemical analysis conducted on excised corneal tissue [7] [8] [9]. These tests include:

• Molecular genetic testing and analysis: This is not only useful in confirming a suspected diagnosis, but also in establishing the correct diagnosis in unconventional clinical presentations.
• Histopathological tissue analysis under light or electron microscopy, using dyes such as Congo red and Alcian blue [6].
• In vivo confocal microscopy: This allows real time microscopic visualization of ocular structures without tissue sampling.

Genetic counseling with a focus on expected disease progression and management options may be provided to patients and their families. Although prenatal diagnosis via amniocentesis or biopsy is theoretically possible, it is not carried out as the condition is not lethal.

1. Weiss JS, Møller HU, Lisch W, et al. The IC3D classification of the corneal dystrophies. Cornea 2008;27 Suppl 2:S1-83.
2. Pandrowala H, Bansal A, Vemuganti GK, Rao GN. Frequency, distribution, and outcome of keratoplasty for corneal dystrophies at a tertiary eye care center in South India. Cornea. 2004;23(6):541-546.
3. Shah SS, Al-Rajhi A, Brandt JD, et al. Mutation in the SLC4A11 gene associated with autosomal recessive congenital hereditary endothelial dystrophy in a large Saudi family. Ophthalmic Genet. 2008;29(1):41-45.
4. Bron AJ. Genetics of the corneal dystrophies: what we have learned in the past twenty-five years. Cornea. 2000;19(5):699-711.
5. Poulaki V, Colby K. Genetics of anterior and stromal corneal dystrophies. Semin Ophthalmol. 2008;23(1): 9-17.
6. Waring GO, 3rd, M.M. Rodrigues, Laibson PR. Corneal dystrophies. I. Dystrophies of the epithelium, Bowman's layer and stroma. Surv Ophthalmol. 1978;23(2):71-122.
7. Santo RM, Yamaguchi T, Kanai A, Okisaka S, Nakajima A. Clinical and histopathologic features of corneal dystrophies in Japan. Ophthalmology. 1995;102(4):557-567.
8. Aldave AJ. The genetics of the corneal dystrophies. Dev Ophthalmol. 2011;48:51-66.
9. Fujiki K, Nakayasu K, Kanai A. Corneal dystrophies in Japan. J Hum Genet. 2001;46(8):431-435.