Corneal dystrophies

Authors: Pr Éric Gabison (lead author) and Dr Youssef Abdelmassih — ophthalmology, cornea & ocular surface. Updated 2026.

Corneal dystrophies are abnormalities that are often characterized by being:

• Hereditary (frequently autosomal dominant)
• Progressive
• Bilateral: exceptions being posterior polymorphous corneal dystrophy (PPCD) and Lisch dystrophy
• More or less symmetric
• Without neovascularization

The best-defined mutation is that of the transforming growth factor beta induced gene (TGFBI), located at 5q31 and encoding kerato-epithelin. The protein binds to corneal collagen types I, II, III and IV. It is mutated in various dystrophies extending from Bowman's layer down to the deep stroma. A single mutation in the same protein can give rise to several phenotypes:

Thiel-Behnke

Granular type 3: Reis-Bücklers

Granular type 1

Granular type 2

Lattice type 1

Lattice type 3

The deposits resulting from this mutation are either granular, amyloid, or mixed. All of these dystrophies share the characteristic of recurring after grafting.

Furthermore, mutations at the same codon can produce different appearances, as illustrated by codon 124:

• Arginine replaced by cysteine → lattice dystrophy type 1
• Arginine replaced by leucine → Reis-Bücklers
• Arginine replaced by histidine → Avellino dystrophy (granular type 2)

Patients with a dystrophy may present to the ophthalmologist for various reasons:

• Decreased visual acuity
• Ocular pain and redness
• Family history of dystrophy
• Routine examination
• Refractive problems

The corneal dystrophies that may cause recurrent erosions (pain, photophobia, blepharospasm in the second half of the night and on waking in the morning) or even clinical pictures suggestive of a corneal infection are:

• Cogan dystrophy +++
• Reis-Bücklers
• Thiel-Behnke
• Meesmann
• Lattice dystrophy
• Subepithelial mucinous dystrophy
• Gelatinous dystrophy
• Granular type 1
• Granular type 2
• Macular dystrophy

Classification

The anatomical–histological classification is often used:

• Anterior:
• Epithelium
• Meesmann dystrophy
• Lisch epithelial dystrophy
• Epithelium–basement membrane (product of the basal layer of the epithelium)
• Cogan
• Gelatinous drop-like dystrophy
• Bowman's layer and anterior stroma with TGFBI mutation
• Granular type 3: Reis-Bücklers, or in English corneal dystrophy of Bowman's layer type I (CDB-1)
• Thiel-Behnke, or CDB-2, or honeycomb dystrophy.
• Stroma:
• TGFBI mutation
• Granular:
• Type 1
• Type 2
• Lattice dystrophy
• No TGFBI mutation:
• Macular
• Schnyder crystalline dystrophy
• Congenital stromal dystrophy
• Fleck dystrophy
• Posterior amorphous corneal dystrophy
• Pre-Descemet dystrophy
• Endothelial
• Fuchs
• PPCD
• CHED

Update — international classification (IC3D)

The reference classification today is that of the International Committee for Classification of Corneal Dystrophies (IC3D), established in 2008 and then revised in 2015 (edition 2; Weiss et al., Cornea 2015;34:117-159) and in 2024 (edition 3; Weiss et al., Cornea 2024;43:466-527). Based on the cellular origin of the deposits, it divides the dystrophies into four groups: (1) epithelial and subepithelial dystrophies, (2) epithelial-stromal TGFBI dystrophies, (3) stromal dystrophies, and (4) endothelial dystrophies. This grouping notably sets apart the TGFBI dystrophies, which involve several corneal layers rather than just one.

In addition, each entity is assigned a level of evidence, ranging from category 1 (a dystrophy fully demonstrated clinically, histopathologically and genetically) to category 4 (a suspected or insufficiently defined entity). Edition 3, freely accessible, incorporates publications from 2014 to 2023 and updates 22 standardized templates, each accompanied by the gene and locus when they are known.

General notes by group

Update — the TGFBI gene and the epithelial-stromal dystrophies

Several dystrophies that were once classified separately share a single cause: mutations in the TGFBI gene (formerly BIGH3, encoding keratoepithelin), located on chromosome 5q31. The IC3D classification groups them under the term TGFBI epithelial-stromal dystrophies. The main genotype-phenotype correlations are:

• R124C → lattice dystrophy type I (LCD1);
• R555W → granular dystrophy type I (Groenouw I, GCD1);
• R124H → granular dystrophy type II or Avellino dystrophy (GCD2);
• R555Q → Thiel-Behnke dystrophy;
• R124L → Reis-Bücklers dystrophy.

A single codon (124 or 555) can thus produce distinct phenotypes depending on the substitution. Genetic diagnosis is particularly useful before refractive surgery: corneal laser surgery (LASIK, PRK) is contraindicated in TGFBI dystrophy — notably GCD2/Avellino — because it causes an abrupt worsening of the deposits, even in previously asymptomatic heterozygous carriers.

Therapeutic update — phototherapeutic keratectomy (PTK)

Excimer laser phototherapeutic keratectomy (PTK) allows photoablation of superficial deposits and treatment of recurrent erosions. It is the treatment of choice for the superficial anterior dystrophies — Reis-Bücklers and Thiel-Behnke — whose deposits are accessible. For lattice, granular, Avellino, and macular dystrophies, it provides transient visual improvement, but recurrence over the treated area is frequent (as a rough guide, about 47% at ~2 years for Reis-Bücklers dystrophy, and less for the lattice and granular forms).

PTK can be repeated without compromising the outcome and often makes it possible to delay grafting. In cases of deep stromal involvement, keratoplasty (deep anterior lamellar or penetrating) remains indicated, although the dystrophy may still recur on the graft.

The stromal dystrophies are divided into two groups, the TGFBI-positive and the TGFBI-negative. In addition, they are often due to deposits at the stromal level.

With the new 2015 classification, CHED type I (AD) was reclassified as posterior polymorphous corneal dystrophy; as a result, CHED is now an exclusively AR dystrophy.

Atlas of dystrophies