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.

• Orthostatic Hypotension

  hypotension, perspiration dysfunction Severe mask-like facial paresis with gradual onset of facial drooping, protruding lips and pendulous ears (due to amyloid deposition and secondary muscular dysfunction) Pathology Sub-Bowman layer deposits of amyloid [eyewiki.aao.org]

  Systemic manifestations include cranial and peripheral neuropathies, which can result in facial paresis, loss of peripheral vibration sense and touch, orthostatic hypotension, and/or cardiac conduction abnormalities. [emedicine.medscape.com]

• 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

  In posterior polymorphous corneal dystrophy small vesicles appear at the level of Descemet membrane. Most patients remain asymptomatic and corneal edema is usually absent. [en.wikipedia.org]

  In CHED (and other endothelial dystrophies like Fuchs’ dystrophy), a loss of endothelial cells results in a buildup of fluid in the corneal stroma (edema). [reviewofophthalmology.com]

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

  For this reason, it is unclear whether PDCD is a dystrophy or degeneration. 66-68 Fuchs’ endothelial corneal dystrophy (FECD) presents with corneal guttata, stromal edema and oftentimes, endothelial pigment. [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]

• Paresis

  […] dysfunction) Lagophthalmos POAG Associated systemic findings: Dry, itchy skin Laxity of the facial skin Intermittent proteinuria (nephrotic syndromes) Cardiac conduction abnormalities, orthostatic hypotension, perspiration dysfunction Severe mask-like facial paresis [eyewiki.aao.org]

  Systemic manifestations include cranial and peripheral neuropathies, which can result in facial paresis, loss of peripheral vibration sense and touch, orthostatic hypotension, and/or cardiac conduction abnormalities. [emedicine.medscape.com]

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.

• Ground Glass Appearance

  Granular Type 1 Dystrophy -stromal dystrophy - small, well demarcated hyaline deposits in the stroma -"ground glass" appearance; prominent centrally ; -will stain red with Masson trichrome dye -manifests early; rarely visual problems; can coalesce (keratoplasty [studyblue.com]

  While in the beginning stages there are clear spaces between lesions, over time these spaces opacify and take on a ground glass appearance. [eyewiki.aao.org]

  Congenital hereditary endothelial corneal dystrophy is characterized by a diffuse ground-glass appearance of both corneas and markedly thickened (2–3 times thicker than normal) corneas from birth or infancy. [en.wikipedia.org]

  With progression of the disease to the second stage, the entire stroma becomes oedematous, giving the cornea a ground-glass appearance. [aop.org.uk]

Treatment Treatment Options: Penetrating keratoplasty can be successful in restoring vision. Grafts have been reported to remain clear for up to 36 years in more than half of the patients in one series but opacities recurred in others. [disorders.eyes.arizona.edu]

[…] problems; can coalesce (keratoplasty) Granular Type 2 ( Avellino ) Dystrophy -hyaline deposits, but also linear or snow-flake like amyloid deposits - not a lattice dystrophy, but looks like it -more dense centrally ; can coalesce (keratoplasty) -laser treatment [studyblue.com]

(c) Fine subepithelial opacities recurred 1 year after the treatment (4/11/2000). (d) Diffuse subepithelial opacities 2 years after the treatment (8/7/2002). [nature.com]

Helps you make optimal use of the newest drug therapies, including Anti-VEGF treatment for wet ARMD and bevacizumab treatment for complications of diabetes. [books.google.com]

Most importantly, genetic testing provides information about prognosis in an individual patient, counseling for families of the affected patient, risk assessment for patients who are undergoing transplantation with respect to disease recurrence, and can [eyeworld.org]

Regraft is possible, but the long-term prognosis is worse than for the original graft. Keratoprosthesis (artificial cornea) can be placed if grafts fail repeatedly. [merckmanuals.com]

Prognosis Of all the stromal corneal dystrophies, macular corneal dystrophy results in the earliest visual loss. This visual loss is due to the lack of clear spaces between the denser gray-white macular opacities. [emedicine.medscape.com]

The etiology is genetic, although inheritance patterns vary. Corneal stromal dystrophy (CSD) includes a number of disorders such as macular, granular, reticular, lattice, fleck, and congenital stroma dystrophies. [symptoma.com]

Incidence/Prevalence: Macular dystrophy is much less common than BIGH3 dystrophies Etiology: Macular dystrophy exhibits an autosomal recessive pattern of inheritance. [missionforvisionusa.org]

Pathophysiology: The etiology of Terrien's marginal degeneration is poorly understood. [oogziekenhuis.me]

Etiology There has not been a specific causal etiology described to date. [eyewiki.aao.org]

Etiology Fleck corneal dystrophy is caused by a mutation in the PIKFYVE gene (2q34). Diagnostic methods Lesions are mostly minute and symmetrical. [orpha.net]

Because we only had one case of macular dystrophy, any conclusion about epidemiological data could be misleading. [scielo.br]

Summary Epidemiology Prevalence of this form of corneal dystrophy is not known. FCD affects males and females equally. Clinical description The condition may occur throughout life and has been reported in children as young as 2 years of age. [orpha.net]

Epidemiology of corneal blindness in developing countries. J Refract Corneal Surg 1991; 7: 436-39. 11. W. John Armitage. Preservatin of human cornea. Transfus Med Hemother 2011; 38: 143-7. 12. [jpma.org.pk]

Epidemiology Frequency United States Macular corneal dystrophy is uncommon, but areas with the highest prevalence include parts of the United States. [emedicine.medscape.com]

Further elaboration on the possible genetic, histopathologic, pathophysiologic and biochemical correlation is required to study the nature of the condition. [ojoonline.org]

The identification of the mutation responsible for the corneal dystrophy is a critical step toward understanding the pathophysiology of the formation of the deposits. [reviewofoptometry.com]

Pathophysiology: The etiology of Terrien's marginal degeneration is poorly understood. [oogziekenhuis.me]

Although the pathophysiology of age-related cataracts is not fully understood, the above mentioned changes are well known to be involved in this pathology. [neurohope.ro]

[…] dystrophy: A review. 61 Aggarwal S...Karcioglu ZA 29604391 2018 5 Long-term clinical outcome of femtosecond laser-assisted lamellar keratectomy with phototherapeutic keratectomy in anterior corneal stromal dystrophy. 61 Lee J...Moon NJ 28611133 2018 6 Pathophysiological [malacards.org]

After early healing of the corneal erosion preventive treatment consists of sodium chloride 5% drops (brand name Muro 128) and artificial tear lubricating drops (e.g. [mastereyeassociates.com]

Supported in part by an unrestricted departmental grant from Research to Prevent Blindness, Inc., New York, New York. The authors thank Drs. [healio.com]

Prevention There are no preventive measures for corneal dystrophies, because they are genetic in origin. Genetic counseling is available for affected families and can be very helpful for support and information. [yoursightmatters.com]

The sample was transferred at 4°C and stored in culture medium that contained Dextran to prevent swelling. During X-ray data collection the sample was wrapped in plastic membrane and was placed between Mylar windows to prevent dehydration. [journals.plos.org]

Beyond the POLARIS TGFBI test, the team in Singapore is currently working on a topical medication that will not only dissolve the aggregates in the cornea, but also prevent protein aggregation. [eyeworld.org]

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9. Fujiki K, Nakayasu K, Kanai A. Corneal dystrophies in Japan. J Hum Genet. 2001;46(8):431-435.