Table 1.
Classification of Corneal dystrophies.
| Region | Name of Dystrophy | Gene | Gene Locus | Mode of Inheritance | IC3D Category | Age of Onset | Symptoms | Visual Acuity | Clinical Appearance of the Cornea |
|---|---|---|---|---|---|---|---|---|---|
| Epithelial and Subepithelial Dystrophies | Epithelial basement membrane dystrophy (EBMD) | TGFBI | 5q31 | Sporadic | 1 | Adult | Corneal erosion, slightly distorted vision | Mild visual reduction | Thickening of the epithelium, round or oval opacities, and lines. |
| Epithelial recurrent erosion dystrophy (ERED) | COL17E1 | 10q23 | Autosomal Dominant | 3 | 1st Decade | Stinging, burning, painful corneal erosion, photophobia | Sometimes impaired | Epithelial erosion | |
| Subepithelial mucinous corneal dystrophy (SMCD) | Unknown | unknown | Autosomal Dominant | 4 | 1st Decade | Painful incidence of recurrent corneal erosion | Progressive loss of vision | Bilateral subepithelial opacities and haze, mostly denser centrally, involving the entire cornea | |
| Meesmann corneal dystrophy (MECD) | KRT3, KRT12, | 12q13, 17q12 | Autosomal Dominant | 1 | Early childhood | Mild erosion and reduced sensation of the cornea | Rarely blurred vision | Multiple, tiny, distinct epithelial vesicles extend to the limbus and are mostly cumulated in the interpalpebral area. | |
| Lisch epithelial corneal dystrophy (LECD) | Unknown | Xp22.3 | X-linked Dominant | 2 | Childhood | symptomatic or blurred vision if the pupillary zone is involved | Sometimes impaired | Localized epithelial opacities of various patterns: whorls, bands, flame, feather shaped. | |
| Gelatinous drop-like corneal dystrophy (GDLD) | TACSTD2 (M1S1) | 1p32 | Autosomal Recessive | 1 | 1st to 2nd Decade | Distorted vision, photophobia, scratchy sensation, redness, tearing | Marked visual impairment | Appearance of subepithelial lesions, indicating extremely hyperpermeable corneal epithelium, Superficial vascularization, stromal opacification | |
| Bowman Layer Dystrophies | Reis–Buckler’s corneal dystrophy (RBCD) | TGFBI | 5q31 | Autosomal Dominant | 1 | Childhood | Painful incidence of recurrent corneal erosion | Progressive deuteriation of vision | Replacement of bowman layer by sheet like connective tissue with granular deposits, which extends to subepithelial stroma. |
| Thiel–Behnke corneal dystrophy (TBCD) | TGFBI | 5q31 | Autosomal Dominant | 2 | Childhood | Painful incidence of recurrent corneal erosion | Gradual visual impairment | Symmetrical subepithelial reticular (honeycomb) opacities in the central cornea; which can progress to deep stromal layers and corneal periphery. | |
| Stromal Dystrophies | Lattice corneal dystrophy (LCD) | TGFBI | 5q31 | Autosomal Dominant | 1 | 1st Decade | Stinging, burning, Painful incidence of recurrent corneal erosion | Progressive visual impairment | Thin branching refractile lines or subepithelial ovoid dots in the central cornea, diffuse stromal, ground-glass haze develops later |
| Granular corneal dystrophy (Type 1 and 2) | TGFBI | 5q31 | Autosomal Dominant | 1 | Childhood; early as 2 years of age | Frequent corneal erosion, photophobia, glare. | Decrease in visual acuity as opacification progresses with age. | Well-defined granular opacities are observed that don’t extend to the limbus. Type 2 can add snowflakes and lattice lines between the granules. | |
| Macular corneal dystrophy (MCD) | CHST6 | 16q22 | Autosomal Recessive | 1 | Childhood | Painful incidence of recurrent corneal erosion, reduced corneal sensitivity, photophobia | Severe visual impairment between 10–30 years. | Thinning of the cornea, in advanced stage corneal endothelium is affected and the Descemet membrane develops guttate excrescences. Limbus to limbus stromal haze, which later spreads to superficial, central, elevated white opacities. | |
| Schnyder Corneal Dystrophy (SCD) | UBIAD1 | 1p36 | Autosomal Dominant | 1 | Childhood to 2nd or 3rd decade | Reduced corneal sensitivity, glare increases, disproportionate decrease of photopic vision, may have hyperlipoproteinemia (type IIa, III, or IV) | Visual acuity decreases with age | Initial signs include central corneal haze and/or subepithelial crystals (>23 years), arcus lipoids (23–38 years), mid-peripheral panstromal haze (after 38 years) | |
| Congenital Stromal Corneal Dystrophy (CSCD) | DCN | 12q21.33 | Autosomal Dominant | 1 | Congenital | Irregular and cloudy appearance of the cornea, reduced visual acuity, increased glare | Moderate to severe visual loss | Diffuse, bilateral, corneal clouding with flake-like, whitish stromal opacities throughout the stroma, pachymetry demonstrates increase in thickness. | |
| Fleck Corneal Dystrophy (FCD) | PIKFYVE | 2q34 | Autosomal Dominant | 1 | Congenital | Asymptomatic | Normal | Small, translucent, discoid opacities that are scattered sparsely throughout without affecting the central cornea. Involvement of the asymmetric or unilateral corneal. | |
| Posterior Amorphous Corneal Dystrophy (PACD) | KERA, LUM, DCN, EPYC | 12q21.33 | Autosomal Dominant | 3 | 1st Decade, early as 16 weeks, possibly congenital nature | Mildly effected visual acuity | Mild visual reduction | Diffused grayish-white sheet like opacities in the posterior part of stroma, corneal thinning (>380 µm), flat corneal topography (<41.00 D) and hyperopia in the centroperipheral form. | |
| Descemets Membrane and Endothelial Dystrophies | Fuchs Endothelial Corneal Dystrophy (FECD); early and late-onset | COL8A2 | 1p34.3–p32, 13pTel–13q12.13, 15q, 18q21.2-q21.32 | Autosomal Dominant | 1, 2 | 4th decade or later | Epiphora due to recurrent corneal erosion, photophobia, pain, epithelial/stromal edema. | Progressive visual impairment | Diffuse thickening of Descemet membrane with excrescences (guttae). Endothelial cells sparse and atrophic |
| Posterior Polymorphous Corneal Dystrophy (PPCD); Type 1, 2, 3 and 4 | OVOL2, COL8A2, ZEB1, GRHL2 | 20p11.23, 1p34.3–p32.3, 10p11.2, 8q22.3 | Autosomal Dominant | 2, 1 | Childhood | Stromal clouding, endothelial decomposition that is often asymptomatic | Rarely extensive and progressive visual impairment | Deep corneal lesions that can be nodular, vesicular or blister-like. Edema of the stromal and epithelial layer, endothelial decomposition | |
| Congenital hereditary endothelial dystrophy | SLC4A11 | 20p13 | Autosomal Recessive | 1 | Congenital | Stromal clouding, blurred vision, photophobia | Blurring vision | Corneal thickening, clouding of the cornea, elevated IOP | |
| X-linked Endothelial Corneal Dystrophy | Unknown | Xq25 | X-chromosomal Dominant | 2 | Congenital | Blurring vision | Blurred vision in males | Cloudy cornea only in males, moon crater–like endothelial changes |
TGFBI, Transforming growth factor beta-induced; KRT3, Keratin 3; COL8A2, collagen type VIII alpha 2; ZEB1, two-handed zinc-finger homeodomain transcription factor 8; SLC4A11, solute carrier family 4 member 11; PIP5K3, Phosphatidylinositol-3-phosphate/phosphatidylinositol 5-Kinase type III; DCN; Decorin, UBIAD1; UbiA prenyltransferase domain containing 1, CHST6, Carbohydrate sulfotransferase 6 gene; GSN, Gelsolin; TACSTD2, tumor associated calcium signal transducer, KERA, deletion of keratocan; LUM, lumican; EPYC, epiphycan; PIKFYVE, phosphoinositide kinase, FYVE finger containing; OVOL2, Ovo like zinc finger 2; GRHL2, Grainyhead-like transcription factor 2.