IC3D Classification of Corneal Dystrophies-Edition 3

Abstract

Purpose: The International Committee for the Classification of Corneal Dystrophies (IC3D) was created in 2005 to develop a new classification system integrating current information on phenotype, histopathology, and genetic analysis. This update is the third edition of the IC3D nomenclature.

Methods: Peer-reviewed publications from 2014 to 2023 were evaluated. The new information was used to update the anatomic classification and each of the 22 standardized templates including the level of evidence for being a corneal dystrophy [from category 1 (most evidence) to category 4 (least evidence)].

Results: Epithelial recurrent erosion dystrophies now include epithelial recurrent erosion dystrophy, category 1 ( COL17A1 mutations, chromosome 10). Signs and symptoms are similar to Franceschetti corneal dystrophy, dystrophia Smolandiensis, and dystrophia Helsinglandica, category 4. Lisch epithelial corneal dystrophy, previously reported as X-linked, has been discovered to be autosomal dominant ( MCOLN1 mutations, chromosome 19). Classic lattice corneal dystrophy (LCD) results from TGFBI R124C mutation. The LCD variant group has over 80 dystrophies with non-R124C TGFBI mutations, amyloid deposition, and often similar phenotypes to classic LCD. We propose a new nomenclature for specific LCD pathogenic variants by appending the mutation using 1-letter amino acid abbreviations to LCD. Pre-Descemet corneal dystrophies include category 1, autosomal dominant, punctiform and polychromatic pre-Descemet corneal dystrophy (PPPCD) ( PRDX3 mutations, chromosome 10). Typically asymptomatic, it can be distinguished phenotypically from pre-Descemet corneal dystrophy, category 4. We include a corneal dystrophy management table.

Conclusions: The IC3D third edition provides a current summary of corneal dystrophy information. The article is available online at https://corneasociety.org/publications/ic3d .

FIGURE 1.

Epithelial basement membrane dystrophy (EBMD). A, Map-like changes. B, Intraepithelial dot opacities (Cogan cysts) underlying map-like figures. C, Fingerprint lines, best visualized with retroillumination. D, Multiple crowded blebs (Bron), only visible in retroillumination. E and F, Light microscopy shows excessive basement membrane material (arrowheads) between the distorted epithelium and the intact Bowman layer to form sheets corresponding to maps (E) and redundant folds corresponding to fingerprint lines (F) (E, Masson trichrome; F, Periodic acid–Schiff, bar = 200 μm). G, In vivo confocal microscopy demonstrates abnormal hyperreflective intraepithelial basement membrane material within suprabasal and basal epithelial cell layers (400 × 400 μm). H, Spectral domain OCT scan shows presence of hyperreflective dots (intraepithelial pseudocysts) within the epithelial layer. Figures 1A, B, C, D, E, F, and G from Figures 1A, B, C, D, E, F, and G in Weiss JS, Møller HU, Aldave AJ, et al. IC3D Classification of Corneal Dystrophies—Edition 2. Cornea. 2015;34:117–159.

FIGURE 2.

Epithelial recurrent erosion dystrophies (EREDs). A, In the first decades of life, the cornea appears normal without any dystrophy-specific signs after recurrent epithelial erosion. B, Bilateral central and paracentral opacities in the right (i) and left (ii) corneas of a 67-year-old with ERED and COL17A1 mutation. C, Light microscopy of the 67-year-old in (B) with keloid pannus visible between the basal epithelium and the locally destroyed (therefore absent) Bowman layer. PAS, bar = 100 μm. In several places, the epithelium is loosely attached (black arrowhead) to the basement membrane which also demonstrates breaks (white arrowhead) (Gly1052 COL17A1 mutation). D, Light microscopy: In advanced age, the Bowman layer (arrowhead) is partially destroyed and pannus (pan) is found between the basal epithelium and the Bowman layer (PAS, × 200 μm). E, Electron microscopy of pannus with numerous fibroblasts. Figures 2A and D from Figures 2A and C in Weiss JS, Møller HU, Aldave AJ, et al. IC3D Classification of Corneal Dystrophies—Edition 2. Cornea. 2015;34:117–159. Figure 2E from Figure 2 in Lisch W, Bron AJ, Munier FL, et al. Franceschetti hereditary recurrent corneal erosion. Am J Ophthalmol. 2012;153:1073–81.e4.

FIGURE 3.

Subepithelial mucinous corneal dystrophy (SMCD). A, Slit lamp biomicroscopy reveals that diffuse subepithelial opacities and haze are densest centrally. B, Light microscopy: a band of increased staining is present beneath the epithelium. The Bowman layer is thin (Alcian blue, ×40). Photograph courtesy of Robert Feder MD. Figures 3A and B from Figures 3A and B in Weiss JS, Møller HU, Aldave AJ, et al. IC3D Classification of Corneal Dystrophies—Edition 2. Cornea. 2015;34:117–159.

FIGURE 4.

Meesmann corneal dystrophy (MECD). A, In direct illumination, diffuse gray, superior opacity with a distinct border is apparent. B, With retroillumination, the same eye demonstrates that the opacity pattern is composed of multiple, solitary transparent microcysts. C, Multiple, solitary transparent microcysts in retroillumination. D, Light microscopy: intraepithelial cysts, sometimes extruding onto the corneal surface, contain amorphous material probably comprised of degenerated epithelial cells. The basement membrane is thickened (Alcian blue and hematoxylin and eosin stain, × 400). E, Electron microscopy: cyst containing intracytoplasmic fibrillar peculiar substance, with surrounding tangles of filaments. F, In vivo confocal microscopy shows hyporeflective areas corresponding to microcysts in the basal epithelial layer and round hyperreflective structures (400 × 400 μm). G, Spectral domain OCT shows an irregular thickness and diffuse hyperreflectivity of the epithelium. Figures 4A and B from Figure 4B in Weiss, JS, Møller HU, Lisch W, et al. The IC3D Classification of the Corneal Dystrophies. Cornea. 2008;27(suppl 2):S1–S42. Figures 4C, D, E, and F from Figures 4C, D, E, and F in Weiss JS, Møller HU, Aldave AJ, et al. IC3D Classification of Corneal Dystrophies—Edition 2. Cornea. 2015;34:117–159.

FIGURE 5.

Lisch epithelial corneal dystrophy (LECD). A and B, Diffuse grayish epithelial opacities form radial, feathery, or club-shaped patterns. C, Opacification consists of crowded, transparent microcysts in retroillumination. D, Light microscopy: pronounced vacuolization of the epithelial cells, particularly in outer layers (hematoxylin and eosin stain, ×250). E, Electron microscopy: discloses coalescent intracellular vacuolization of the wing cells. Some of these vacuoles coalesce to form empty spaces within the cytoplasm of the epithelial cells (×4000). F, In vivo confocal microscopy shows intraepithelial hyperreflective dystrophic areas containing hyporeflective round structures, sharply demarcated from normal epithelial areas (400 × 400 μm). Figures 5A, B, D, E, and F from Figures 5A, B, D, E, and F in Weiss JS, Møller HU, Aldave AJ, et al. IC3D Classification of Corneal Dystrophies—Edition 2. Cornea. 2015;34:117–159.

FIGURE 6.

Gelatinous drop-like corneal dystrophy (GDLD). A, Band keratopathy type. B, Mulberry type. C, Fluorescein staining shows an extremely hyperpermeable corneal epithelium, here without superficial punctate keratopathy or erosion. D, Kumquat-like diffuse stromal opacity. E, Light microscopy: massive amyloid in a subepithelial lesion (arrowheads) extending to the midstromal cornea, bar = 400 μm (direct fast scarlet, ×10). Figures 6A, B, and D from Figures 6B, A, and C in Weiss, JS, Møller HU, Lisch W, et al. The IC3D Classification of the Corneal Dystrophies. Cornea. 2008;27(suppl 2):S1–S42. Figures 6C and E from Figures 6C and E in Weiss JS, Møller HU, Aldave AJ, et al. IC3D Classification of Corneal Dystrophies—Edition 2. Cornea. 2015;34:117–159.

FIGURE 7.

Reis–Bücklers corneal dystrophy (RBCD). A, Confluent irregular, geographic-like opacities. B, Geographic opacities extend to the limbus and deeper stroma in a more advanced case. C, Light microscopy: Masson trichrome stains keratohyalin intensely red beneath the epithelium and between superficial stromal lamellae. Note characteristic destruction of the Bowman layer. Deeper red spots (asterisk) are an artifact of lamellar keratoplasty (R124L TGFBI mutation), bar = 200 μm. D, Electron microscopy: broad band of irregularly arranged, subepithelial rod-shaped bodies (×3000). E, In vivo confocal microscopy shows a granular, highly reflective material without any shadow within the basal epithelium (R124L TGFBI mutation) (400 × 400 μm). F, Recurrent deposits within the corneal graft 15 years after penetrating keratoplasty. Figure 7A from Figure 7A in Weiss, JS, Møller HU, Lisch W, et al. The IC3D Classification of the Corneal Dystrophies. Cornea. 2008;27(suppl 2):S1–S42. Figures 7B, C, D, and E from Figures 7B, C, D, and E in Weiss JS, Møller HU, Aldave AJ, et al. IC3D Classification of Corneal Dystrophies—Edition 2. Cornea. 2015;34:117–159.

FIGURE 8.

Thiel–Behnke corneal dystrophy (TBCD). A, Initial signs of mild honeycomb appearance. B, Intensive honeycomb opacity pattern in advanced disease (R555Q TGFBI mutation). C, Corneal honeycomb opacity in a 42-year-old with genetically confirmed TBCD (R555Q TGFBI mutation). D, Light microscopy: varying thickness of the epithelium because of a thickened abnormal subepithelial fibrous layer (arrowheads) that replaces the Bowman layer and has a characteristic sawtooth-like surface. Masson trichrome, bar = 200 μm. E, Transmission electron microscopy: subepithelial curly filaments with a thickness of 10 nm (x 50,000). F, In vivo confocal microscopy shows abnormal hyperreflective material with homogeneous reflectivity, round edges, and dark shadows within the basal epithelium (400 × 400 μm). G, Anterior segment OCT from the same 42-year-old in (C) demonstrates a sawtooth pattern of hyperreflective material in the Bowman layer. Figures 8A, B, C, D, E, F, and G from Figures 8A, B, Ci, D, E, F, and Cii in Weiss JS, Møller HU, Aldave AJ, et al. IC3D Classification of Corneal Dystrophies—Edition 2. Cornea. 2015;34:117–159.

FIGURE 9.

Classic lattice corneal dystrophy (classic LCD). Direct (A) and retroillumination (B) of early lattice corneal dystrophy with dots and fine lattice lines (R124C TGFBI mutation). C, Subepithelial ground glass haze of the central and inferior cornea and diffuse lattice lines in advanced LCD (R124C TGFBI mutation). D, Dots and paracentral lattice lines in retroillumination (R124C TGFBI mutation). E, Light microscopy: Congo red prominently stains a continuous layer of amyloid (asterisk) that underlies and partially destroys the Bowman layer and intrastromal amyloid deposits (arrowheads) corresponding to lattice lines (R124C TGFBI mutation). F, Light microscopy: this same section viewed with polarized light confirms deposits are birefringent and red–green dichroic, thus amyloid, bar = 200 μm. G, In vivo confocal microscopy image shows filaments corresponding to lattice lines within the stroma (400 × 400 μm). Figure 9D from Figure 10A in Weiss, JS, Møller HU, Lisch W, et al. The IC3D Classification of the Corneal Dystrophies. Cornea. 2008;27(suppl 2):S1-S42. Figures 9A, B, C, E, F, and G from Figures 9A, B, C, E, F, and G in Weiss JS, Møller HU, Aldave AJ, et al. IC3D Classification of Corneal Dystrophies—Edition 2. Cornea. 2015;34:117–159.

FIGURE 10.

Lattice corneal dystrophy (LCD) variants. Five broad phenotypes. A, LCD variant phenotype that recapitulates the early onset and fine lattice lines of classic LCD in a 7-year-old (LCD-L569R TGFBI mutation). B, Intermediate sometimes late-onset LCD variant phenotype demonstrating lattice lines that are thick, ropy, and more prominent than in classic LCD, as seen in direct (B) and retroillumination (C), in a 50-year-old (LCD-T621P TGFBI mutation). D and E, Same phenotype as (B and C) but with asymmetric progression between the 2 eyes of 1 patient (LCD-H626R TGFBI mutation, the second most common and geographically widespread LCD variant). F, Late-onset LCD variant phenotype demonstrating amyloid deposits primarily located in the deep stroma, thus not leading to corneal erosions, with lattice lines that are infrequent or inconspicuous in an 85-year-old (LCD-R496W TGFBI mutation). G, Intermediate-onset superficial LCD variant phenotype in which amyloid is mainly deposited at Bowman layer level resulting in a geographic pattern that may be misdiagnosed as EBMD, RBCD, or TBCD, with infrequent or indistinct lattice lines in a 40-year-old (LCD-H626P TGFBI mutation). H, Intermediate to late-onset LCD variant phenotype in which amyloid deposits are mostly dot-shaped and comma-shaped and show variation in form and depth, with lattice lines in a 74-year-old (LCD-L527R TGFBI mutation). I, Same phenotype as (H) but with infrequent and indistinct lattice lines in a 65-year-old (LCD-L565P TGFBI mutation). J and K, Same phenotype as (H and I), late stage with opacification of central cornea from white more granular-like deposits in a 60- and 82-year-old (LCD-L527R TGFBI mutation and LCD-A546D TGFBI mutation, respectively). Figure 10A reprinted from Figure 2C in Warren JF, Abbott RL, Yoon MK, et al. A new mutation (Leu569Arg) within exon 13 of the TGFBI (BIGH3) gene causes lattice corneal dystrophy type I. Am J Ophthalmol. 2003;136:872–878 with permission from Elsevier. Figures 10B and C used with permission of Slack, Inc. from Figures A(a) and A(b) in Lee J, Ji YW, Park SY, et al. Delayed onset of lattice corneal dystrophy Type IIIA due to a novel T621P mutation in TGFBI. J Refract Surg. 2016;32:356; permission conveyed through Copyright Clearance Center, Inc. Figures 10D and E reprinted from Figures 1A and B in Zenteno JC, Correa-Gomez-V, Santacruz-Valdez C, et al. Clinical and genetic features of TGFBI-linked corneal dystrophies in Mexican population: description of novel mutations and novel genotype–phenotype correlations. Exp Eye Res. 2009;89:172–177 with permission from Elsevier. Figure 10F reproduced from Figure 1B in Kawasaki S, Yagi H, Yamasaki K, et al. A novel mutation of the TGFBI gene causing a lattice corneal dystrophy with deep stromal involvement. Br J Ophthalmol. 2011;95:150–151, with permission from BMJ Publishing Group Ltd. Figure 10 G from Figure 1A in Liskova P, Klintworth GK, Bowling BL, et al. Phenotype associated with the H626P mutation and other changes in the TGFBI gene in Czech families. Ophthalmic Res. 2008;40:105–108. Copyright © 2008 Karger Publishers, Basel, Switzerland. Figure 10H and K from Figures 1A and 3A in Hirano K, Hotta Y, Nakamura M, et al. Late-onset form of lattice corneal dystrophy caused by Leu527Arg mutation of the TGFBI gene. Cornea. 2001;20:525–529. Figure 10I from Figure 1B in Ołdak M, Szaflik JP, Ścieżyńska A, et al. Late-onset lattice corneal dystrophy without typical lattice lines caused by a novel mutation in the TGFBI gene. Cornea. 2014;33:294–299. Figure 10J from Figure 3A in Irusteta L, Ramírez-Miranda A, Navas-Pérez A, et al. Detailed phenotypic description of stromal corneal dystrophy in a large pedigree carrying the uncommon TGFBI p.Ala546Asp pathogenic variant. Ophthalmic Genet. 2022;43:589–593. Reprinted by permission of Taylor & Francis Ltd.

FIGURE 11.

Systemic amyloidosis with corneal findings (Meretoja syndrome). A, Lax, mask-like facies consequent to cranial nerve VII palsy. B, Lattice lines are less numerous than in classic and variant LCD, start peripherally and spread centrally. Figures 11A and B from Figures 11A and B in Weiss JS, Møller HU, Aldave AJ, et al. IC3D Classification of Corneal Dystrophies—Edition 2. Cornea. 2015;34:117-159.

FIGURE 12.

Granular corneal dystrophy, type 1 (GCD1). A, In a child, early subepithelial verticillate-like opacities are evident by retroillumination and direct illumination. With (B) full direct illumination, (C) slit-beam illumination, and (D) retroillumination, “snowflake” stromal deposits are both discrete and confluent and are axially distributed within the clear intervening stroma. E, After PTK, GCD1 deposits (arrows) are noted to recur in the subepithelial area on slit lamp and OCT. F and G, After DALK, GCD1 deposits (arrows) are noted to recur (F) centrally in the deep posterior graft–host interface (arrows) or (G) peripherally along suture tracks (arrows) on slit lamp and OCT. H, Light microscopy: Masson trichrome highlights full-thickness deposits of keratohyalin in the corneal stroma (R555W TGFBI mutation, bar = 240 μm). I, In vivo confocal microscopy (400 × 400 μm) shows abnormal hyperreflective opacities in snowflake and trapezoidal shapes within the stroma. J, Spectral domain OCT shows multiple hyperreflective stromal deposits, with well-defined borders, located from deep epithelium to Descemet membrane, in a 32-year-old male patient with GCD1. Figures 12A and H from Figures 12A and E in Weiss JS, Møller HU, Aldave AJ, et al. IC3D Classification of Corneal Dystrophies—Edition 2. Cornea. 2015;34:117–159.

FIGURE 13.

Granular corneal dystrophy, type 2 (GCD2). A, A 13-year-old with sparse white dots and genetic confirmation of GCD2. B, Direct illumination (i) and retroillumination (ii) demonstrate branching, star-shaped, spiny, and ring-like deposits. C, GCD2 with superficial, translucent flattened breadcrumb opacities beneath the Bowman layer. Denser icicles and disc-like and ring-like opacities are also present (R124H TGFBI mutation). D, Homozygote with denser and confluent opacities (R124H TGFBI mutation). E, Light microscopy: sub-Bowman and anterior stromal keratohyalin deposits (arrowheads) stain red with Masson trichrome (R124H TGFBI mutation). Note that the deeper stromal layers do not have keratohyalin granules (asterisk). In the deep stroma, small amyloid deposits stain with Congo red (inset) (bar = 300 μm, inset = 200 μm). F, In vivo confocal microscopy shows abnormal hyperreflective stromal deposits with a snowflake or trapezoidal shape within the corneal stroma (400 × 400 μm). G, Spectral domain OCT shows irregular hyperreflective deposits located in the Bowman layer and in the anterior stroma in a 34-year-old patient with GCD2. H, GCD2 exacerbated status post-LASIK with prominent stromal opacities. Figures 13Bi and Bii from Figure 13B in Weiss, JS, Møller HU, Lisch W, et al. The IC3D Classification of the Corneal Dystrophies. Cornea. 2008;27(suppl 2):S1–S42. Figures 13A, C, D, E, and F from Figures 13A, C, D, E, and F in Weiss JS, Møller HU, Aldave AJ, et al. IC3D Classification of Corneal Dystrophies—Edition 2. Cornea. 2015;34:117–159.

FIGURE 14.

Macular corneal dystrophy (MCD). A, Early stage with few central macular opacities. B, Slit lamp photograph demonstrates anterior deposits centrally as well as extension of the deposits to the limbus (arrow) and to the deep stroma down to Descemet membrane peripherally (arrow). C, More diffuse opacities and haze involving the entire stroma in an individual with type 2 MCD (L276P CHST6 mutation). D, Light microscopy: intracellular and extracellular accumulation of glycosaminoglycans (GAGs) at all levels of stroma and corneal endothelium. Subepithelial fibrous tissue also contains GAGs. Colloidal iron, ×20. E, In vivo confocal microscopy image (400 × 400 μm) showing hyperreflective abnormal areas within the stroma. Some dark striae can be observed within the hyperreflective material. F, Spectral domain OCT shows hyperreflective throughout the corneal stroma (at the site of the stromal deposits), associated with hyperreflective opacities in the Bowman layer and irregular stromal surface, in a 29-year-old patient with MCD. Figure 14A from Figure 14A in Weiss, JS, Møller HU, Lisch W, et al. The IC3D Classification of the Corneal Dystrophies. Cornea. 2008;27(suppl 2):S1-S42. Figures 14C, D, and E from Figures 14C, D, and E in Weiss JS, Møller HU, Aldave AJ, et al. IC3D Classification of Corneal Dystrophies—Edition 2. Cornea. 2015;34:117–159.

FIGURE 15.

Schnyder corneal dystrophy (SCD). A, Central stromal opacity in early SCD without crystals (UBIAD1 mutation). B, Early subepithelial central crystalline deposit (UBIAD1 mutation). C, Central corneal opacity with arcus lipoides. D, Central corneal opacity, subepithelial crystalline ring, midperipheral haze, and arcus lipoides. E, Noncrystalline central diffuse opacity pattern with clearer area centrally, midperipheral haze, and prominent arcus lipoides in 39-year-old patient (UBIAD1 mutation). F, Noncrystalline disc-like central opacity, midperipheral haze, and prominent arcus lipoides in a 72-year-old patient with SCD with UBIAD1 mutation. G, Light microscopy: Oil Red O stains innumerable tiny lipid droplets within the corneal stroma in a frozen section that has not undergone processing for paraffin embedding, which would dissolve the lipids and make the staining negative, bar = 100 μm. H, Electron microscopy: empty crystalline space within a basal cell representing cholesterol deposit dissolved during dehydration stage of embedding process (×10,000) (SCD with crystals). I, In vivo confocal microscopy (400 × 400 μm) shows abnormal hyperreflective homogeneous spindle-shaped deposits within the subepithelial zone (SCD with crystals). J, Right cornea of a 66-year-old patient with SCD (i) with nonconfluent subepithelial crystals (arrow) sparing the visual axis. OCT (ii) demonstrates corresponding areas of subepithelial lucency (arrows) representing subepithelial cholesterol crystalline deposits. K, Left cornea of a 57-year-old patient with SCD (i) with panstromal opacification (arrow) and no crystals with corresponding OCT (ii) showing panstromal hyperlucency representing panstromal lipid deposits (flanked by arrows). Figures 15B and C from Figures 15B and A in Weiss, JS, Møller HU, Lisch W, et al. The IC3D Classification of the Corneal Dystrophies. Cornea. 2008; 27(suppl 2):S1–S42. Figures 15A, D, E, F, G, H, and I from Figures 15A, D, E, F, G, H, and I in Weiss, JS, Møller HU, Aldave AJ, et al. The IC3D Classification of the Corneal Dystrophies—Edition 2. Cornea. 2015 34:117–159.

FIGURE 16.

Congenital stromal corneal dystrophy (CSCD). A, Diffuse clouding with flake-like opacities throughout the stroma in a 4-year-old patient (c.967delT DCN frameshift mutation). B, Light microscopy: The cornea is markedly thickened with stromal lamellae that are separated from each other in a regular manner with some areas of deposition, bar = 200 μm. C, Electron microscopy: Apparently normal collagen lamellae are separated by areas of amorphous substance with small filaments (arrows) characteristic for the condition (original magnification ×20). Figures 16A, B, and C from Figures 16A, B, and C in Weiss, JS, Møller HU, Aldave AJ, et al. The IC3D Classification of the Corneal Dystrophies—Edition 2. Cornea. 2015 34:117–159.

FIGURE 17.

Fleck corneal dystrophy (FCD). In 2 different patients, dandruff-like opacities are visualized throughout the stroma using (A), broad oblique illumination and indirect illumination and (B), at varying depths in the slit lamp photograph. Figures 17A and B from Figures 17A and B in Weiss, JS, Møller HU, Lisch W, et al. The IC3D Classification of the Corneal Dystrophies. Cornea. 2008;27(suppl 2):S1–S42.

FIGURE 18.

Posterior amorphous corneal dystrophy (PACD). A, Central deep stromal/pre-Descemet opacity with some degree of peripheral extension interrupted by a few clear bands in the midperipheral cornea. B, Slit beam demonstrates decreased corneal thickness and posterior stromal lamellar opacification. C, Light microscopy: colloidal iron-positive material (arrowheads) accumulates extracellularly in the posterior stroma, bar = 100 μm. D, (i), Central deep stromal/pre-Descemet opacity interrupted with 2 clearer bands (arrows) and a clear ring in the more peripheral cornea (a 3.0 Mb deletion including 12q12.32-q21.33). (ii) Spectral domain OCT in this patient reveals a continuous hyperreflective band in the posterior stroma anterior to the endothelium (arrow). Figures 18A, B, and C from Figures 18A, B, and C in Weiss JS, Møller HU, Aldave AJ, et al. IC3D Classification of Corneal Dystrophies—Edition 2. Cornea. 2015;34:117–159.

FIGURE 19.

Central cloudy dystrophy of François (CCDF) or posterior crocodile shagreen. No information about family history available. Axially distributed, polygonal gray–white stromal opacities separated by linear areas of clear cornea. Figure 19 from Figure 19A in Weiss, JS, Møller HU, Lisch W, et al. The IC3D Classification of the Corneal Dystrophies. Cornea. 2008;27(suppl 2):S1–S42.

FIGURE 20.

Pre-Descemet corneal dystrophy (PDCD). A, With broad-beam illumination, punctate opacities anterior to Descemet membrane are apparent. B, Slit-beam illumination of the same eye demonstrating punctate opacities anterior to Descemet membrane. C, Punctiform and polychromatic pre-Descemet corneal dystrophy (PPPCD, PRDX3 mutation). Slit-beam illumination demonstrates large uniform pre-Descemet opacities. D, Confocal microscopy of the same patient from (C) demonstrates hyper-reflective deposits at the level of Descemet membrane. E, OCT demonstrates hyperreflectivity posteriorly (arrow). Figures 20A and B from Figures 20A and B in Weiss, JS, Møller HU, Aldave AJ, et al. The IC3D Classification of the Corneal Dystrophies—Edition 2. Cornea. 2015 34:117–159.

FIGURE 21.

Fuchs endothelial corneal dystrophy (FECD). A, Corneal guttae in retroillumination (i) and slit lamp view (ii). B and C, Epithelial edema with bullae and stromal edema due to endothelial decompensation. D, Light microscopy: corneal guttae in the form of focal excrescences at the level of the endothelium; thickening of Descemet membrane (arrowhead); stromal and intraepithelial edema. PAS, bar = 200 μm. E, Light microscopy: Descemet membrane endothelial keratoplasty (DMEK) specimen shows (i) thickened Descemet membrane (black arrowhead) with guttae (asterisks), which are more prominent in the central portion of the DMEK specimen (cen) when compared with the peripheral (per) section, and an attenuated endothelial cell layer (white arrowhead), PAS stain. (ii), In a corneal specimen from a different eye, the original Descemet membrane (black arrowhead) is further thickened by layers of reactively secreted looser (lr) and denser (dr) basement membrane material that buries, and in this routine HE section mostly hides earlier guttae (asterisks), the latter of which are revealed in a PAS-stained section (iii). Note sparse and flattened endothelial cells (white arrowhead); bars = 50 μm. F, In vivo confocal microscopy shows polymegethism and pleomorphism of endothelial cells associated with round hyporeflective structures sometimes containing reflective material and corresponding to guttae (400 × 400 μm). Figures 21B and C from Figures 21D and B in Weiss, JS, Møller HU, Lisch W, et al. The IC3D Classification of the Corneal Dystrophies. Cornea. 2008;27(suppl 2):S1–S42. Figures 21D and F from Figures 21D and E in Weiss, JS, Møller HU, Aldave AJ, et al. The IC3D Classification of the Corneal Dystrophies—Edition 2. Cornea. 2015;43:117–159.

FIGURE 22.

Posterior polymorphous corneal dystrophy (PPCD). A, Endothelial plaque-like lesions. B, Irregular crater-like figures on Descemet membrane viewed with specular reflection. C, Endothelial railroad track alteration (arrows). D, Verrucous lesions (arrows) of the posterior corneal surface. E, Changes in PPCD, such as vesicular lesions (arrows), are typically better detected with retroillumination. F, Light microscopy: PAS stain (i) and Masson trichrome (ii) show that the endothelium is replaced with flat epithelial-like cells which grow focally as more than 1 layer of cells (i; asterisk), forming blisters (ii; arrowheads) and occasionally elevated strands. The posterior stroma may show pits or discontinuities in Descemet membrane (i; arrowhead), bar = 100 μm. G, Light microscopy: penetrating keratoplasty specimen (i) shows an uneven, mostly thin, Descemet membrane (black arrowhead) covered by a much thicker collagenous layer (asterisk) secreted by aberrant endothelial cells (white arrowheads), some of which are located within the membrane, in a 6-year-old child with PPCD3 from a ZEB1 mutation. ii and iii, Corresponding findings at age 8 years in DMEK specimen of the fellow eye, consisting mostly of the thick collagenous layer (asterisks) with sparse endothelial cells (white arrowheads). Some endothelial cells are located within the collagenous membrane or have detached from the membrane, to which fragments of the thin Descemet membrane attach (black arrowheads) (PAS, bar = 100 µm (i); PAS (ii) and Masson trichrome stain (iii), bars = 50 µm). H, In vivo confocal microscopy showing vesicular lesions and band-like structures with irregular edges within the endothelium associated with polymegethism of endothelial cells (400 × 400 μm). I, Spectral domain OCT shows irregular hyperreflectivity within Descemet membrane and endothelial layer, corresponding to abnormal multilayer endothelial cells in a 50-year-old female patient with PPCD. Figure 22B from Figure 22B in Weiss, JS, Møller HU, Lisch W, et al. The IC3D Classification of the Corneal Dystrophies. Cornea. 2008;27(suppl 2):S1–S42. Figures 22A, Fi, Fii, and H from Figures 22A, Di, Dii, and E in Weiss, JS, Møller HU, Aldave AJ, et al. The IC3D Classification of the Corneal Dystrophies—Edition 2. Cornea. 2015;34:117–159.

FIGURE 23.

Congenital hereditary endothelial dystrophy (CHED). A and B, Right and left corneas, respectively, of a 30-year-old woman with CHED (homozygous T271M SLC4A11 mutation). Photographs courtesy of Dr. Majid Moshirfar. C, Slit-beam photograph demonstrating diffuse stromal thickening (homozygous SLC4A11 mutation). D, Light microscopy: edema of basal epithelial cells with subepithelial lacunae (open arrowhead) and breaks (arrowhead) in the Bowman layer, bar = 80 μm. E, Thickened Descemet membrane with no visible endothelial cells, bar = 50 μm. F, In vivo confocal microscopy (400 × 400 μm) shows polymegethism of endothelial cells. Cell cores are enlarged and hyperreflective with poorly defined contours. Figure 23C from Figure 23B in Weiss, JS, Møller HU, Lisch W, et al. The IC3D Classification of the Corneal Dystrophies. Cornea. 2008;27(suppl 2):S1–S42. Figures 23A, B, D, and E from Figures 23A, B, D, and E in Weiss JS, Møller HU, Aldave AJ, et al. IC3D Classification of Corneal Dystrophies—Edition 2. Cornea. 2015;34:117–159.

FIGURE 24.

X-linked endothelial dystrophy (XECD). A, Male infant with congenital corneal haze. B, The same patient at age 12 years now showing moon crater–like endothelial changes in indirect illumination. C, His mother with moon crater–like endothelial changes in retroillumination. D, Light microscopy: scarce endothelial cells (arrowheads) with an atypical appearance, bar = 100 μm. E, Electron microscopy: degenerative endothelial cell adjacent to denuded area (arrow) of Descemet membrane (DM) (×10,000). N, nucleus. Figures 24A, C, D, and E from Figures 24A, B, C, and D in Weiss JS, Møller HU, Aldave AJ, et al. IC3D Classification of Corneal Dystrophies—Edition 2. Cornea. 2015;34:117–159.