This is a classic exam-type case for the FRCOphth and similar examinations. The patient is a young adult undergoing a corneal graft.
(Click on the images to see them full-sized)
This is a low power view. Non-keratinising stratified squamous epithelium covers the convex surface. Beneath it lies Bowman’s layer (not readily visible at this power) and then the stroma. Note the ragged appearance of the (concave) posterior stromal surface. This specimen does not include Descemet’s membrane and the endothelium: the operation was a deep anterior lamellar keratoplasty (DALK), and the patient’s Descemet’s membrane/endothelium were left in place.
The epithelial thickness is a little irregular. I view this simplistically as epithelium (which proliferates relatively quickly) compensating for irregularities in the underlying stroma. Of course, the noteworthy abnormality is the deposits of eosinophilic (deep pink) material within the stroma. They are present superficially, at the level of Bowman’s layer, as well as in the deeper stroma, and quite variable in size.
In the annotated image, I’ve marked the deposits with asterisks.
A higher power view shows the deposits to have sharp outlines. Clinically, they are classically described as “crumb-like”, and I think this applies on histology as well. In areas they obliterate Bowman’s layer. There is stromal scarring, but no vascularisation or inflammation.
In the annotated image, I’ve marked the location of Bowman’s layer in blue. It is interrupted by the deposits.
This is Masson Trichrome, a histochemical stain. The deposits are positive (red), indicating the presence of “hyaline material.” The appearance is typical of granular dystrophy.
Granular dystrophy is one of the three classic corneal stromal dystrophies (the other two being lattice and macular). It is caused by mutations in a gene known variously as keratoepithelin, BIGH3 or TGFBI (that’s a capital “i” not a “1”), and it is one of the chromosome 5q31-linked corneal dystrophies. Mutations in the same gene may give rise to other dystrophies including lattice, Reis-Bücklers and Avellino. These dystrophies histologically show various combinations and distributions of amyloid and hyaline material subepithelially, within Bowman’s layer and in the stroma. While it’s good practice to provide a specific diagnosis (especially for exam purposes!), if I’m unsure precisely which dystrophy I’m looking at (ie when it doesn’t clearly fall into one of the more common categories), I may end up lumping the case into “a 5q31-linked dystrophy” with a suggestion to evaluate the patient genetically.
Here are some relevant articles:
This is the OMIM (Online Mendelian Inheritance in Man) entry on TGFBI. It includes examples of phenotypes.
Histochemistry of corneal granular dystrophy by Professor Alec Garner. It’s an old article, but comprehensive. I can’t resist including it because Professor Garner was one of my predecessors at the UCL Institute of Ophthalmology.
Mutation Hot Spots in 5q31-Linked Corneal Dystrophies by Korvatska et al. This article covers genetic investigations of a number of families with 5q31-linked dystrophies.
Extremely varied phenotypes in granular corneal dystrophy type 2 heterozygotes. This article by Han et al has a nice collection of clinical images (with, as the title suggests, considerable variation).
The above papers are free to access. My standard go-to reference when checking a corneal dystrophy is the IC3D classification of corneal dystrophies–edition 2 by Weiss et al. Unfortunately, it’s behind a paywall, but it’s worth getting if you expect to see corneal dystrophies regularly. Alternatively, The IC3D Classification of the Corneal Dystrophies (edition 1) is free to access. Just be aware it’s not the most up to date version.