TABLE 2.
Lattice Corneal Dystrophy Variants
| DNA Change | Protein | Exon | FAS1 | Earliest Onset (Decade) | Erosions | Depth | Lines | Reported as | Clinical Description | Countries/Ethnicity | Clinical Publications (Listed by PMID) | Experimental Publications (Listed by PMID) |
| c.370C>T | p.R124C | 4 | 1 | Early 1st | Yes | All eventually | Thin | LCDI | See LCD template (classic LCD) | Australia; Bangladesh; Brazil; Bulgaria; Canada; China; France; Greece; Germany; Hungary; India; Japan; Mexico; Singapore (Malay descent); Spain; Switzerland; Turkey; Ukraine; the United Kingdom; the United States | 9054935, 9463327, 9497262, 9559741, 9592740, 9886734, 10798644, 10832717, 10844062, 11024425, 11095060, 11262611, 11146721, 11297504, 11413412, 11741113, 11923233, 11927442, 12138697, 12072720, 12225829, 12586172, 12770961, 15013897, 15017378, 15564760, 15623763, 16008913, 16118514, 16329070, 16380889, 16809844, 16710170, 16331487, 17063427, 16440005, 17768377, 17846354, 17982422, 18470323, 18615206, 19001012, 19062536, 19350511, 20161820, 20360992, 20664689, 20680100, 20806046, 21921985, 21462384, 21887843, 21835759, 22355247, 22773977, 22876129, 24801599, 25055147, 25876897, 25785536, 25932442, 26949635, 26748743, 27348782, 27737463, 27829782, 28393022, 28358433, 29085627, 30098247, 30805211, 31555324, 33513810, 34937214, 35484844, 35985662 | 21948648, 22080335, 23861389, 25557343, 26207300, 30387319 |
| c.1486C>T | p.R496W | 11 | 3 | Late 9th | No | Mainly deep | Minor | LCDIV | Corneal haze with many isolated or fused refractile opacities, mostly dots, some lattice lines, mainly in deep stroma | Japan | 20974628 | |
| c.1501C>A | p.P501T | 11 | None | Late 7th | Yes | Mainly anterior | Thick | LCDIIIA Japanese | Asymmetric; late-developing thick ropy lattice lines; linear thick branching rod-like opacities from limbus to limbus and discrete nodular deposits; thick ropy lattice lines | China; Japan; South Korea | 9497262, 10218700, 10832717, 11004271, 11024425, 11501939, 12400061, 16809844, 21462384, 23884333, 26748743 | |
| c.1504A>G | p.M502V | 11 | 4 | Late N/A | N/A | Unclassifiable | N/A | LCD atypical | Unclassifiable phenotype because of extensive corneal opacifications, 32-year-old daughter with small round, refractive deposits predominately in the anterior stroma | Mexico | 19303004 | |
| c.1514T>A | p.V505D | 11 | 4 | Early 1st | Yes | Mainly anterior | Thin | LCDI | Symmetrical opacities more prominent in the central cornea, in younger patients a few thin lattice lines anteriorly and axially with light central stromal clouding, with increasing age opacities spread posteriorly and centrifugally, 1–2 mm clear peripheral zone | China | 15838722 | |
| c.1526T>C | p.L509P | 11 | 4 | Early 2nd | Yes | Mainly anterior | Thin | LCDI; LCDIIIA; RBCD | Cloudy and geographic primarily subepithelial opacities, small granules in anterior stroma; confluent irregular and coarse geographic subepithelial and anterior stromal opacities; diffuse subepithelial opacities in direct illumination, paracentral stromal lattice lines in retroillumination; a network of thick lattice lines and dots; diffuse grayish-white subepithelial deposits, distinct refractile lattice lines spreading to the periphery; geographic opacities at Bowman layer level, lattice lines in deeper layers | France; Germany; South Korea | 19001012, 21617751, 25055147, 26748743, 35683443 | |
| c.1526T>G | p.L509R | 11 | 4 | Early 2nd | Yes | Mainly anterior | Thin | LCD atypical; EBMD | Irregularly shaped maps, faint gray–white patches 1 to several millimeters in size, map-dot-fingerprint changes; bilateral subepithelial geographic map-like opacities, lattice lines; geographic opacities at Bowman layer level, lattice lines in deeper stroma | France | 16652336, 21617751 | |
| c.1553T>C | p.L518P | 12 | 4 | Early 2nd | Yes | Mainly anterior | Thin | LCDI; LCDI Atypical | Dense superficial opacity, fine lattice lines in superficial stroma and midstroma, age 17 years fine lattice lines in superficial stroma and midstroma; age 15 round subepithelial central opacities, later extend into peripheral and deep stroma | Japan | 10482106, 10837380, 11095060, 12138697, 21948648 | |
| c.1553T>G | p.L518R | 12 | 4 | N/A | N/A | N/A | N/A | LCD//IIIA | Advanced subepithelial and stromal amyloid deposits | Switzerland (Swiss, Italian, or French descent) | 11923233 | |
| c.1565T>A | p.I522N | 12 | 4 | Early 2nd | Yes | Mainly anterior | Thin | LCDI | Distinct lattice lines and diffuse opacification in subepithelial and anterior stroma, thick lattice lines, and diffuse grayish-white clouding that partly hides central lattice lines | China; Mexico | 19956413 | |
| c.1580T>G | p.L527R | 12 | 4 | Late 7th | No | Mainly deep | Thick in some eyes | LCDIII; LCDIV; LCD deep | Asymmetric; large nodular gray–white deposits from deep stroma to pre-Descemet in pupillary zone or large filiform and lattice line opacities in various parts of stroma; deep stromal nodular deposits and thick lattice lines; distinct lattice lines; lattice-shaped granular deposits in asymmetric patterns, nodulolinear deposits mainly in anterior stroma, less linear and macular opacities; bifurcating thick lattice lines in superficial stroma in midperiphery, extending to central stroma, no nodular deposits; discrete and nodular opacities in deep central stroma, no visible lattice lines; haze composed of isolated or fused refractile opacities, most dot-like, some lattice-like; several bifurcating thick lattice lines in superficial to midstroma; discrete nodular opacities in deep stroma | Japan; South Korea | 9799082, 10832717, 11024425, 11095060, 11501939, 11413411, 12138697, 15022435, 15770959, 15923518, 16453189, 17846354, 20357204, 21191728, 21835759, 22876129, 24505203, 26748743 | 21948648 |
| c.1612A>C | p.T538P | 12 | 4 | Early 1st | Yes | Mainly anterior | Thin | LCDI | Lattice lines in central stroma; numerous fine lattice lines and dots in anterior central stroma | Australia; China | 16809844, 21462384, 35985662 | 22605926 |
| c.1613C>G | p.T538R | 12 | 4 | Early 1st | Yes | Mainly anterior | N/A | LCDI/IIIA | LCDI-like | Switzerland (American descent); Ukraine | 11923233, 19062536 | |
| c.1616T>A | p.V539D | 12 | 4 | Late 6th | N/A | Mainly anterior | N/A | N/A | Lattice lines in anterior stroma; anterior and midstromal lattice lines | India | 15623763 | |
| c.1617T>A | p.F540S | 12 | 4 | Late 5th | No | Mainly deep | Thick | N/A | Thick ropy lattice lines | Germany; China | 15790870 | 25557343 |
| c.1625C>G | p.P542R | 12 | 4 | Late 5th | Yes | Anterior to deep | Thick | LCD atypical | Distinct lattice lines; relatively thick lattice lines from the limbus in superficial and deep stromal layers, stromal haze in 1 eye | South Korea | 22876129, 26748743 | |
| c.1631A>G | p.N544S | 12 | 4 | Late 7th | No | Mainly deep | Thin | LCDIV atypical | Distinct lattice lines; dots and lattice lines in midstroma to deep stroma; tiny nodular deposits and thin lattice lines in midstroma | Japan; South Korea | 11024425, 15559315, 15770959, 26748743 | |
| c.1636G>A | p.A546T | 12 | 4 | Intermediate 4th | Yes | Anterior to deep | Thick | LCDIIIA French | Age 55 years predominantly central thick ropy lattice lines, some small nodular opacities, diffuse haze between the lines, age 35 years superficial lattice lines | Brazil; China; France | 10682981, 11297504, 11927442, 16440005, 21462384 | 25910219, 34097874 |
| c.1637C>A | p.A546D | 12 | 4 | Intermediate 3rd | No | Deep to anterior | Minor to thin | LCDIIIA; PCA; GCD1/2 | Multiple polymorphic, polygonal, refractile chipped ice-like gray and white opacities, occasional deep filamentous lines without distinct lattice pattern but producing a small focal network; polymorphic chipped ice-like opacities in posterior stroma, occasional filamentous lines without distinct lattice pattern; polymorphic stromal opacities, distinct branching filamentous lattice opacities, small granular opacities in peripheral cornea; atypical GCD1-like; five predominantly GCD2-like phenotype, one GCD1-like, one LCD-like phenotype; typical IIIA phenotype with focal central and distinct relatively thick lattice lines; polymorphic opacities predominantly in central cornea; short lineal deposits, without a clear lattice pattern; polymorphic opacities in central stroma, conspicuous interdigitating branching filamentous opacities and multiple lattice lines in peripheral stroma, also small granular opacities in peripheral cornea | China; Germany; Mexico; Taiwan; the United States | 15177960, 17063427, 17893671, 19001012, 19303004, 21462384, 22355247, 28393022, 35470743, 35484844 | 23592924 |
| c.1640T>C | p.F547S | 12 | 4 | Intermediate 4th | N/A | Deep to anterior | Minor | PCA | Snowflake-like central deposits, fine linear and chipped-ice deposits, more abundant in central cornea, extending throughout stroma, numerous pre-Descemet deposits | Hungary | 17982422 | |
| c.1643G>C | p.R548P | 12 | 4 | Late 7th | N/A | Deep to anterior | Minor | LCD variant; RBCD | Diffuse central corneal haze with edema without visible lattice lines | South Korea | 26748743 | |
| c.1649T>C | p.L550P | 12 | 4 | N/A | N/A | Deep to anterior | Thin | GCD2 | Deposits typical of GCD2 with bilateral symmetrical discrete lattice lines in peripheral cornea; fine peripheral lattice lines with powdery central lesions, another patient with lattice and granular stromal deposits | Mexico; South Korea | 19303004, 33513810 | |
| c.1673T>C | p.L558P | 12 | 4 | Intermediate 3rd | N/A | Deep to anterior | Thin | LCDIV; PCA | Initially scarce central punctiform 50–100 μm stromal deposits, later confluent, white–gray under direct illumination, typical branched filamentous opacities 0.5–3.0 μm length with no haze in some patients, in 1 patient with granular opacities arranged in irregular round shape in lower cornea; polymorphic corneal amyloidosis with deep stromal opacities | Spain; Ukraine | 19062536, 31056827 | |
| c.1673T>G | p.L558R | 12 | 4 | Late 6th | No | Deep to anterior | Minor | LCD | Fine translucent gray–white branching stromal lattice lines and dots at all depths | Czech Republic | 27028151 | |
| c.1694T>A | p.L565H | 13 | 4 | Late 5th | N/A | N/A | Minor to thin | LCDIIIA; LCD atypical | Haze and diffuse opacities in central stroma, lack of typical lattice lines, oval-shaped or short comma-shaped spots with indistinct margins within deep stroma; diffused opacities in central stroma, fine lattice lines in paracentral and peripheral stroma; small diffused translucent punctate opacities and a few chipped ice-like lattice lines; uniformly diffused punctate opacities in central stroma, fine lattice lines mostly in paracentral stroma | China | 31555324, 35484844 | |
| c.1694T>C | p.L565P | 13 | 4 | Late 6th | Yes | Deep to anterior | Minor | LCD atypical | Round, oval, and short comma-shaped opacities with indistinct margins, no visible lattice lines | Poland | 24473223 | |
| c.1706T>A | p.L569Q | 13 | 4 | Late 6th | Yes | N/A | Thick | LCDI | Large lattice lines; typical lattice lines | South Korea | 25932442, 26748743 | |
| c.1706T>G | p.L569R | 13 | 4 | Early 1st | Yes | Mainly anterior | Thin | LCDI | Diffuse subepithelial and anterior stromal clouding, typical fine branching lattice lines in midperipheral anterior stroma; age 7 years numerous fine refractile lattice lines and dots in central cornea; typical fine branching lattice lines, area of central opacification | The United States (Swiss, Italian, and Irish descent) | 14597039 | |
| c.1715A>G | p.H572R | 13 | 4 | Intermediate 3rd | Yes | Anterior to deep | Thin to thick | LCDI | Asymmetric; elevated subepithelial opacities, diffuse haze, thin to thick lattice lines, diffuse haze; elevated subepithelial opacities, thick lattice lines, diffuse haze; subepithelial and stromal white dots, thin linear irregular branching refractile lines; mild cases resemble LCDI with refractile lattice lines from central stroma to periphery with limbal sparing, in advanced cases lattice lines usually obscured by diffuse stromal opacity, difficult to distinguish from leukoma, corneal surface eventually becomes irregular because of elevated thick lattice lines; lattice lines thicker and less crowded than in LCDI, in anterior stroma yellowish discoloration | Thailand; Chile; China | 17013691, 20161820, 20806046, 31270466, 33513810 | 32637173 |
| c.1772C>T | p.S591F | 13 | 4 | Intermediate 4th | Yes | Deep to anterior | Thick | LCD asymmetric | Asymmetric; translucent subepithelial irregularity, relatively short and thick, branching central lattice lines, extending midperipherally; discrete relatively short and thin branching lattice lines in anterior and midstroma in central stroma | Finland; the United States (Spanish descent) | 33645289, 35315300 | |
| c.1781G>T | p.G594V | 13 | 4 | Late 6th | N/A | Deep | Thick | LCD atypical | Thick lattice lines in deep stroma, extending to limbus | India | 15623763 | |
| c.1828T>G | p.V613G | 14 | 4 | Late 9th | N/A | N/A | N/A | LCD | Corneal opacities, child with small dots and a star-shaped opacity | Algeria | 21617751 | |
| c.1856T>A | p.M619K | 14 | 4 | Late 5th | No | Anterior to deep | Thick | GLCD | In younger individuals, central subepithelial needle-like deposits; in older individuals, polymorphic semiconfluent anterior stromal opacities, combined granular lattice; axially distributed linear branching anterior and midstromal deposits, gray–white on direct illumination and translucent on retroillumination, additionally discrete semiconfluent anterior and midstromal polymorphic deposits; peripheral cornea with linear branching opacities similar to LCDI; dense confluent gray–white anterior and midstromal deposits in central stroma, a few linear extensions of central opacity | The United States (Hispanic) | 18332318 | 28381645 |
| c.1858G>C | p.A620P | 14 | 4 | Intermediate 4th | Yes | Mainly anterior | Thin | LCDIIIA granular | Distinct lattice lines; diffuse superficial haze and extensive lattice lines; focal superficial opacity, thick lattice lines | China; South Korea | 25321938 | |
| c.1859C>A | p.A620D | 14 | 4 | Intermediate 3rd | Yes | Mainly anterior | Thin | LCD variant | Subepithelial and anterior stromal scarring, radially oriented linear opacities in central anterior to midstroma | China; South Korea | 21835759, 26949635, 26748743, 33513810 | |
| c.1861A>C | p.T621P | 14 | 4 | Late 5th | Yes | Mainly anterior | Thick | LCDIIIA | Asymmetric; thick branching ropy lattice lines; thick ropy lattice lines extending to limbus with intervening opacities in central stroma | South Korea | 25932442, 27163623, 35484844 | |
| c.1864A>C | p.N622H | 14 | 4 | Late 5th | No | Anterior to deep | Thick | LCDIIIA; LCD late | Asymmetric; thick central ropy lattice lines | Australia; the United Kingdom | 10328397, 35985662 | 28381645 |
| c.1866T>G/A | p.N622K | 14 | 4 | Intermediate 4th | Yes | N/A | Thick | LCDIIIA | Large, ropy lattice lines in anterior stroma | Switzerland (Italian, South American descent) | 11923233 | |
| c.1867G>C | p.G623R | 14 | 4 | Intermediate 3rd | Yes | Mainly anterior | Minor to thin | LCD | In a young patient, single subtle greyish lattice line; in an older patient, subepithelial map-like opacities in central and midperipheral stroma, 2 branching lattice lines in anterior stroma, delicate thin anterior to midstromal lines in midperipheral cornea | Germany | 19001012 | 28381645 |
| c.1868G>A | p.G623D | 14 | 4 | Intermediate 3rd | Yes | Anterior | Minor to thin | LCDI/IIIA; RBCD; TBCD; EBMD | Tiny discrete linear subepithelial deposits in anterior stroma, middle, and posterior stroma free; patchy subepithelial central stromal haze, a single refractile lattice-like line; several foci of subepithelial haze, a single branching refractile anterior stromal lattice line-like deposit in 1 eye; scattered central patches of subepithelial haze without lattice lines, delicate thin anterior and midstromal lattice lines most dense axially and absent from peripheral 2 mm, a horseshoe-shaped opacification at Bowman layer level in 1 eye; central subepithelial haze, a prominent central subepithelial opacity, very fine branching lattice lines in central anterior stroma, other eye with scattered gray–white subepithelial opacities forming an arrowhead pattern, no lattice lines; subepithelial deposits resembling RBCD; diffuse or geographic superficial stromal opacity, small refractile granules or lines, diffuse axial anterior stromal haze with small lattice lines; geographic pattern of subepithelial haze and tiny granular structures; diffuse subepithelial haze and small refractile structures; subepithelial nodular opacification in a geographic pattern | Switzerland (Swiss, Italian, or French descent); the United Kingdom; the United States | 11923233, 15885785 | |
| c.1870G>A | p.V624M | 14 | 4 | Late 5th | No | Deep to anterior | Thick | LCD | Asymmetric; thick ropy linear opacities in deep stroma, fellow eye with small deep short rod-shaped stromal opacities | The United States | 18385782 | 22155582, 25557343 |
| c.1874T>A | p.V625D | 14 | 4 | Early 2nd | Yes | Anterior | Thin | LCD | Ridgy round pattern of opacities with uneven surface and thin lattice lines; diffuse anterior stromal haze, small granular focal opacities, lattice lines not visible | China | 17765440, 27737463 | |
| c.1877A>C | p.H626P | 14 | 4 | Early 1st | Yes | Anterior | N/A | LCDI/IIIA; early-onset superficial keratopathy | Dense haze, lattice lines; confluent subepithelial opacities; irregular corneal surface, discrete subepithelial gray–white polymorphic opacities project from Bowman layer level into epithelium, with longer duration increasing scarring, neovascularization and calcification with no visible lattice lines | Switzerland (Swiss, Italian, or French descent); Czech; New Zealand | 11923233, 18259096, 18728790 | |
| c.1877A>G | p.H626R | 14 | 4 | Intermediate 3rd | Some | Anterior to deep | Thick | LCDI/IIIA LCDIIIA LCDIIIB; LCDi; LCD asymmetric | Asymmetric; broad lattice lines; broad lattice lines, dense central scarring, initially lower cornea, initially thin lines in fellow eye; subepithelial clumps of translucent material; initial asymmetric stellate deposits in the lower central cornea; thick lattice lines in the whole stromal layer; a band-shaped deposition of amyloid close to Descemet membrane; initially subepithelial stellate deposits in lower central cornea; lattice lines and central patchy deposits; fewer but thicker and deeper lattice lines, extending more to the periphery than those of LCD1; anterior-to-midstromal lattice lines; fine GCD1-like opacities mainly in the central cornea; lattice lines in family, PCA in a sporadic patient; bilateral symmetrical fine translucent lattice lines in the superficial and middle stromal layers; thick lattice lines in peripheral and central cornea with small contralateral stellate or snowflake-like deposits; lattice lines and recurrent diffuse stromal haze; thick lattice lines in deep stroma; thick lattice lines extending toward periphery; delicate fragile rare lattice lines located centrally; thick, distinct lattice lines extending from limbus to limbus accompanied by stromal haze; radially oriented curvilinear opacities; gray–white thick lattice lines extending across the cornea; asymmetric, branching, translucent lattice lines, focally with stromal haze, a single patch peripherally in fellow eye; coarse, branching, lattice lines, with prominent stromal haze, a single patch peripherally in fellow eye; translucent focally delicate and branching, focally coarse deposits associated with stromal haze; GCD2 phenotype; numerous translucent, thick lattice lines in superficial and midstroma in central and peripheral cornea; minor lattice lines predominantly below the visual axis; lattice lines predominantly below the visual axis; gray–white thick lattice lines in deep stroma; thick, ropy lattice lines extending to periphery, superficial scar from recurrent erosions | Canada; China; Finland; France; India; Mexico; Switzerland; Ukraine; Vietnam; the United Kingdom; the United States | 10328397, 10798644, 11146721, 11297504, 11923233, 11927442, 12072720, 12770961, 15623763, 16008913, 16888689, 18728790, 19001012, 19350511, 19303004, 20664689, 21921985, 21835759, 24579556, 24589966, 24801599, 25876897, 26949635, 27348782, 27737463, 28358433, 30851800, 33513810 | 28381645, 28689406, 30387319 |
| c.1892T>A | p.V631D | 14 | 4 | N/A | N/A | Deep to anterior | N/A | LCD deep | Initially stellate pre-Descemet deposits with round Descemet indentations, later radial lattice lines in midstroma, anterior third of stroma mostly intact; opacities typically in central stroma | Switzerland (Italian descent) | 11923233, 23455751 |
EBMD, epithelial basement membrane dystrophy; GCD, granular corneal dystrophy; GLCD, granular-lattice corneal dystrophy; LCD, lattice corneal dystrophy; LCDI, previously called lattice corneal dystrophy, type 1 and now renamed classic lattice corneal dystrophy; LCDi, lattice corneal dystrophy intermediate; PCA, polymorphic corneal amyloidosis; RBCD, Reis-Bücklers corneal dystrophy; TBCD, Thiel-Behnke corneal dystrophy.