Corneal dystrophies are inherited, bilateral, slowly progressive, non-inflammatory disorders characterised by abnormal material deposition within the cornea. They are classified anatomically by the corneal layer affected a framework that directly informs clinical presentation and management. This article covers the four dystrophies most relevant to medical students and junior doctors.

Corneal Anatomy: A Brief Overview

The cornea is a transparent, avascular structure providing approximately two-thirds of the eye’s refractive power. It comprises five layers:

• Epithelium — Outermost protective layer; rapidly regenerates; acts as barrier to infection.
• Bowman’s Layer — Acellular condensed collagen layer; provides structural support.
• Stroma — ~90% of corneal thickness; regularly arranged collagen fibres responsible for transparency.
• Descemet Membrane — Basement membrane of the endothelium; thickens with age.
• Endothelium — Single cell layer lining the posterior cornea; maintains corneal dehydration via active Na⁺/K⁺-ATPase pumps.

This anatomical classification predicts clinical features: anterior dystrophies (epithelium/Bowman’s) cause recurrent erosions; stromal dystrophies cause progressive opacities; endothelial dystrophies cause oedema and visual loss.

1. Epithelial Basement Membrane Dystrophy (EBMD)

Also known as Map–Dot–Fingerprint Dystrophy. Layer affected: Epithelium / epithelial basement membrane.

Pathology

Abnormal basement membrane production leads to poor epithelial adhesion, resulting in irregular epithelial architecture and a predisposition to recurrent erosions. EBMD is the most common corneal dystrophy; it is often discovered incidentally.¹

Symptoms

• Foreign body sensation and eye pain, typically worse on waking (eyelid adheres to loosely adherent epithelium overnight)
• Photophobia and blurred or fluctuating vision
• Recurrent episodes of sharp pain

Slit-Lamp Findings

• Maps — irregular geographic subepithelial lines
• Dots — small intraepithelial microcysts
• Fingerprints — fine concentric whorl-like lines

Management

• Conservative first line: lubricating drops/ointment, hypertonic saline (5% NaCl), night-time lubricants
• Recurrent erosions: bandage contact lens, anterior stromal puncture, or phototherapeutic keratectomy (PTK)²

2. Lattice Corneal Dystrophy

Layer affected: Stroma.

Pathology

Amyloid deposition within the corneal stroma, forming branching lines. The majority of cases are caused by autosomal dominant TGFBI gene mutations (most commonly p.Arg124Cys for Type I).³ Onset is typically in the first or second decade, with progressive corneal opacification.

Symptoms

• Recurrent corneal erosions (often the presenting feature)
• Gradual visual deterioration and photophobia as the stroma hazes

Slit-Lamp Findings

• Branching refractile lines forming a lattice or network pattern
• Central distribution; intervening stroma becomes progressively hazy with time

Management

• Early: lubricating drops, management of recurrent erosions (bandage lens, PTK)
• Advanced: penetrating keratoplasty (PK); recurrence in grafts is recognised²

3. Granular Corneal Dystrophy

Layer affected: Stroma.

Pathology

Hyaline (non-amyloid) material deposits within the stroma, also due to TGFBI gene mutations (p.Arg555Trp for Type I).³ Onset is in childhood or early adulthood with slow progression.

Symptoms

• Often asymptomatic early; vision initially preserved
• Gradual visual decline, glare, and occasionally recurrent erosions in later stages

Slit-Lamp Findings

• Discrete, sharply demarcated white “breadcrumb” or “snowflake” deposits
• Clear intervening stroma — a distinguishing early feature

Management

• Early: observation and lubrication
• Advanced: PTK for superficial deposits; corneal transplantation (PK or DALK) for deeper involvement²

4. Fuchs Endothelial Dystrophy

Layer affected: Endothelium.

Pathology

Progressive, accelerating loss of endothelial cells, impairing the active dehydration mechanism and causing corneal oedema. Most commonly presents after age 50 and is more prevalent in women (approximately 2.5:1 female predominance).⁴ Genetic associations include SLC4A11 and TCF4 repeat expansions in familial cases.⁵

Symptoms

• Blurred vision on waking, improving through the day (overnight corneal swelling increases as evaporation is lost with closed lids)
• Glare and halos around lights
• Pain if epithelial bullae rupture (bullous keratopathy)

Slit-Lamp Findings

• Corneal guttae — drop-like excrescences on Descemet membrane (beaten-metal appearance)
• Stromal oedema and, in advanced disease, epithelial microcysts and bullae

Management

• Early: hypertonic saline drops (5% NaCl), hair-dryer technique to evaporate surface moisture
• Advanced: endothelial keratoplasty — DMEK (Descemet Membrane Endothelial Keratoplasty) is preferred over DSAEK for superior visual outcomes and lower rejection rates²⁶

Summary Comparison

References

1. Werblin TP, Hirst LW, Stark WJ, Maumenee IH. Prevalence of map-dot-fingerprint changes in the cornea. Br J Ophthalmol. 1981;65(6):401–409.

2. Weiss JS, Møller HU, Aldave AJ, et al. IC3D classification of corneal dystrophies — edition 2. Cornea. 2015;34(2):117–159.

3. Munier FL, Korvatska E, Djemai A, et al. Kerato-epithelin mutations in four 5q31-linked corneal dystrophies. Nat Genet. 1997;15(3):247–251.

4. Gain P, Jullienne R, He Z, et al. Global survey of corneal transplantation and eye banking. JAMA Ophthalmol. 2016;134(2):167–173.

5. Wieben ED, Aleff RA, Tosakulwong N, et al. A common trinucleotide repeat expansion within the transcription factor 4 (TCF4, E2-2) gene predicts Fuchs corneal dystrophy. PLoS One. 2012;7(11):e49083.

6. Deng SX, Sanchez PJ, Flores-Morales S, Aldave AJ. Clinical outcomes after Descemet membrane endothelial keratoplasty: a systematic review and meta-analysis. Ophthalmology. 2016;123(11):2376–2386.

Article written by Dr Ali Alseneid, FY1