Anterior dystrophies · Epithelial and subepithelial (basement membrane) dystrophies

Cogan dystrophy

Cues: AD/AR inheritance · graft recurrence +++ high ++ intermediate + low · bold = key terms · Differential diagnosis (blue) and Treatment (amber) boxes.

The most common cause of anterior dystrophy.

Also known as map-dot-fingerprint dystrophy

Genetics: Most often sporadic. AD in hereditary forms.
Mutation: found in the collagen XVII gene, a membranous collagen involved in the basement membrane adhesion system. Cases linked to a TGFBI mutation are probably in reality stromal dystrophies.

Identification of the gene(s) involved in Cogan dystrophy is laborious because the majority of Cogan dystrophies are not truly dystrophies: most map-dot-fingerprint lesions are secondary to chronic inflammation of the ocular surface (e.g. rosacea). Moreover, because most TGFBI-related stromal dystrophies can be complicated by symptoms of recurrent corneal erosion, careful clinical semiological analysis is important to avoid any confusion.

Sex: female predominance (symptomatic forms on a background of dry eye?)
Laterality: Bilateral
Symmetry: Yes
Systemic factors: No
Age of onset: Often in adolescence
Location: Epithelial cells and basement membrane
Appearance: Characterized by reduplications of the basement membrane, which are the source of the abnormalities.

Map: broad intraepithelial reduplication of the basement membrane. The fluorescein appearance is characteristic: regions where the epithelium is thick (abnormal) are covered by a thin layer of fluorescein, even "fluo-negative", whereas normal regions are covered by a thick layer of fluorescein and are therefore brighter and fluorescein-positive (pooling in).
Dot: intraepithelial cysts containing cellular debris and pyknotic nuclei of pearly-white color, often grouped in clusters at the center of the cornea. During their maturation from the basal layers toward the surface, epithelial cells become trapped and die beneath the reduplications of the basement membrane.
To be distinguished from the cysts of Lisch or Meesmann dystrophy, which have an appearance of diffuse opacities (Meesmann) or of a limbal feather-like pattern (Lisch) that is characteristic on direct illumination.
Early Acanthamoeba keratitis presents with epithelial cysts that are sometimes very numerous
Fingerprints: linear zones of basement membrane reduplication, with projections (folds) into the epithelial layer.

Recurrent pain or erosion:

Due to an alteration of the normal mechanism of attachment of epithelial cells to Bowman's layer, induced by the aberrant basement membrane.

Examination of the contralateral eye is essential in cases of recurrent corneal erosion. Whereas "acquired" forms are most often unilateral (plant-material trauma, fingernail injury, etc.), forms secondary to ocular surface inflammation (rosacea, atopic keratoconjunctivitis) may be bilateral without any genetic abnormality being the cause.
Pain appears mainly in the second half of the night (paradoxical sleep or REM sleep) and on waking (opening of the eyelids).

Visual acuity: often preserved unless lesions are present in front of the pupil.

Ancillary investigations:

Confocal microscopy: cysts at the level of the basal layer of the epithelium, hyperreflective folds at the level of the basement membrane, and abnormal corneal nerves.
OCT: the epithelial thickness is irregular, the epithelium is globally hyperreflective, especially superficially, with fine hyperreflective punctate spots. Hyperreflective folds within Bowman's layer, with a reduplicated appearance in places.

Treatment

Medical, with lubrication (morning and night), cycloplegics and osmotic agents, and doxycycline for its anti-inflammatory (anti-metalloproteinase) effect
Contact lenses.
Mechanical debridement of the diseased epithelium (a broad debridement extending beyond the detached zones is recommended) to eliminate the areas of abnormal basement membrane.
Oral tetracycline (doxycycline 50 to 100 mg in 6-week courses, to be repeated if needed).

Tetracyclines are metalloproteinase inhibitors. They reduce the symptoms related to the induction of these enzymes (recurrent corneal erosion, fluctuating vision).

Anterior stromal micropunctures if the lesion is peripheral. This technique is effective in 80% of cases, but the lesion may sometimes extend to adjacent zones. A bent 25-gauge needle is used to avoid deep lesions.
Therapeutic keratectomy with the excimer laser acts by increasing the density of hemidesmosomes at the level of the basement membrane through an increase in anterior stromal fibrosis.