Corneal Dystrophies Made Easy: Layers, Stains and Genes
Last updated: October 2026
There are more than 20 corneal dystrophies, but you only need to know which layer each starts in and a few "odd ones out". The layer predicts the symptoms, the look at the slit lamp, the stain and the operation.
Four rules
1. The layer decides the symptomEpithelium and Bowman: recurrent erosions and pain, often in childhood. Stroma: slowly falling vision and glare. Endothelium: oedema, worse in the morning.
2. The layer decides the operationSuperficial (epithelium, Bowman, anterior stroma): PTK or superficial keratectomy. Stroma with healthy endothelium: DALK. Endothelium: DMEK or DSAEK.
3. Almost everything is autosomal dominantThe exceptions are macular and gelatinous drop-like (recessive), CHED (recessive) and X-linked endothelial dystrophy. Note: Lisch dystrophy, once called X-linked, is now classed as dominant (IC3D 2024).
4. One gene builds a whole familyTGFBI (5q31) causes Reis–Bücklers, Thiel–Behnke, granular 1 and 2, and lattice 1. The amino acid hotspots R124 and R555 decide which one.
The classic stromal trio and their stains
| Granular (type 1) | Lattice (type 1) | Macular | |
|---|---|---|---|
| Deposit | Hyaline | Amyloid | Glycosaminoglycans (keratan sulphate) |
| Stain | Masson trichrome (red) | Congo red: apple-green birefringence; thioflavin T | Alcian blue, colloidal iron |
| Look | Discrete white crumbs, clear stroma in between, periphery spared | Fine branching refractile lines, central | Grey-white hazy spots, cloudy stroma in between, reaching the limbus |
| Thickness | Normal | Normal | Thin |
| Erosions | Occasional | Frequent | Occasional |
| Inheritance | AD (TGFBI R555W) | AD (TGFBI R124C) | AR (CHST6) |
| Vision falls | Late (4th–5th decade) | Middle age | Early (1st–2nd decade) |
Memory hook: Marilyn Monroe Always Gets Her Man in L.A. City: Macular – Mucopolysaccharide – Alcian blue; Granular – Hyaline – Masson; Lattice – Amyloid – Congo red.
Memory hook: Macular is the odd one out in everything: recessive, not TGFBI, whole stroma to the limbus, cloudy in between, thin cornea, earliest loss of vision.
TGFBI hotspots at a glance
| Mutation | Dystrophy | Layer | What to remember |
|---|---|---|---|
| R124C | Lattice type 1 (classic) | Anterior–mid stroma | Amyloid lines; erosions. Over 80 other TGFBI variants give “lattice variants” (IC3D 2024) |
| R124H | Granular type 2 (Avellino) | Anterior stroma | Granular + lattice features; worsens dramatically after LASIK: screen family history before refractive surgery |
| R124L | Reis–Bücklers | Bowman | Geographic opacities; painful erosions from early childhood; recurs early in grafts |
| R555W | Granular type 1 | Anterior stroma | Breadcrumbs with clear spaces |
| R555Q | Thiel–Behnke | Bowman | Honeycomb pattern; curly fibres on electron microscopy |
Memory hook: Codon 124 gives lattice (C), Avellino (H) and Reis–Bücklers (L); codon 555 gives the two neat patterns, granular crumbs (W) and the Thiel–Behnke honeycomb (Q).
Epithelial dystrophies
| Dystrophy | Key features |
|---|---|
| Epithelial basement membrane (EBMD, map-dot-fingerprint, Cogan) | Most common; usually degenerative rather than inherited; maps, dots and fingerprint lines; recurrent erosions; irregular astigmatism that spoils keratometry before cataract surgery |
| Meesmann | Myriad tiny intraepithelial cysts in childhood; keratin genes KRT3 and KRT12; usually mild |
| Lisch | Whorled grey band-shaped epithelium seen best on retroillumination; MCOLN1; now autosomal dominant (IC3D 2024) |
| Epithelial recurrent erosion (ERED) | Erosions from childhood, often improve with age; COL17A1; Franceschetti, Smolandiensis and Helsinglandica are now grouped with it |
| Gelatinous drop-like | Mulberry-like subepithelial amyloid; recessive (TACSTD2); common in Japan; recurs after surgery |
Other stromal dystrophies
- Schnyder: central ring or disc of cholesterol crystals (only in about half), dense arcus, mid-peripheral haze; stains with Oil red O; UBIAD1. Check fasting lipids: many patients have hyperlipidaemia.
- Congenital stromal: flaky cloudy stroma at birth (DCN, decorin). Fleck: tiny asymptomatic flecks throughout (PIKFYVE).
- Posterior amorphous, central cloudy of François, pre-Descemet: mostly asymptomatic posterior haze; PPPCD (punctiform and polychromatic pre-Descemet) is linked to PRDX3.
Endothelial dystrophies
| Dystrophy | Onset | Key features | Gene |
|---|---|---|---|
| Fuchs | Usually after 40; women more often | Central guttae → stromal oedema → epithelial bullae; morning blur. Guttae + oedema → DMEK or DSAEK | TCF4 CTG repeat expansion (late onset); COL8A2 (early onset) |
| Posterior polymorphous (PPCD) | Childhood, often asymptomatic | Vesicles, bands and geographic patches at Descemet; endothelium behaves like epithelium; may cause glaucoma and corectopia | OVOL2, ZEB1, GRHL2 |
| Congenital hereditary endothelial (CHED) | Birth | Bilateral ground-glass corneas, very thick, normal IOP and corneal diameter (vs. congenital glaucoma); nystagmus in severe cases | SLC4A11, recessive |
| X-linked endothelial | Birth (males) | Moon-crater endothelial changes; clouding in males | X-linked |
- Cloudy cornea in a newborn: remember STUMPED: Sclerocornea, Tears in Descemet (birth trauma, congenital glaucoma), Ulcer, Metabolic (mucopolysaccharidoses), Peters anomaly, Endothelial dystrophy (CHED), Dermoid.
- PPCD vs ICE syndrome: both have epithelial-like endothelium. PPCD is bilateral, inherited and found in the young; ICE is unilateral, sporadic, in middle-aged women.
Treatment by layer
| Problem | Options |
|---|---|
| Recurrent erosions (EBMD, ERED, Reis–Bücklers, lattice) | Lubricants, bandage contact lens, hypertonic saline; debridement with diamond burr polishing, anterior stromal puncture, or PTK |
| Anterior stromal deposits (granular, Avellino, Reis–Bücklers, Thiel–Behnke) | PTK first; DALK if deeper; recurrences can be re-treated with PTK |
| Deeper stromal disease (lattice, macular, Schnyder) | DALK (macular may also affect the endothelium, so PK is sometimes needed) |
| Endothelial disease (Fuchs, CHED, PPCD) | DMEK or DSAEK; Descemet stripping only (DSO) with a ROCK inhibitor for selected Fuchs patients |
Where residents slip
- Mixing up the stains: use the Marilyn Monroe line.
- Calling macular dystrophy dominant: it is recessive and not a TGFBI disease.
- Doing LASIK on a patient with faint anterior stromal dots: Avellino dystrophy can explode after LASIK.
- Confusing CHED with congenital glaucoma: CHED has normal IOP and a normal-sized cornea, with no Haab striae.
- Forgetting EBMD before cataract surgery: irregular topography gives wrong K readings and toric IOL errors. Treat the surface first.
Test yourself: flip cards
Quick quiz
Related: Cornea hub, Fuchs dystrophy, Genes and eye diseases, Eye embryology made easy.
Key sources
- Weiss JS, Rapuano CJ, Seitz B, et al. IC3D Classification of Corneal Dystrophies, Edition 3. Cornea. 2024;43(4):466-527
- Weiss JS, Møller HU, Aldave AJ, et al. IC3D classification of corneal dystrophies, edition 2. Cornea. 2015;34(2):117-159
- American Academy of Ophthalmology. Basic and Clinical Science Course, Section 8: External Disease and Cornea (current edition)
📘 Want more exam-ready material? See Most Commons in Ophthalmology on Kindle, or browse all my books.
Looking for an eye specialist in Ahmedabad? Learn about our Eye Department or book a consultation with Dr. Dhaval Patel.