Unsurprisingly, the frequency of corneal graft surgery took a dip last year, when we dealt with around 350 cases rather than our more usual numbers of 500-550. Where did that reduction come from? I’ve just had a quick peruse of our LIMS (Laboratory Information Management System), comparing 2020 with 2018 and 2019. I initially thought that non-urgent cases (such as stromal dystrophies and maybe keratoconus) would be reduced, and that we would see relatively higher numbers of keratitis/perforation and bullous keratopathy (ie sight/eye-threatening and painful conditions). Oddly, “keratitis” and even “perforation” as search terms also came up with fewer hits in 2020. Was there really less infectious keratitis in 2020? Was it treated more conservatively? Or did we simply not receive the specimens (despite RCOphth/RCPath guidance, corneal tissue from patients is sometimes still discarded). Obviously, this is just a snapshot, and I wouldn’t rush to conclusions. If you see corneal disease in your practice, I’d welcome your comments below as to your impressions.
Here’s a trio of recent cases: all failed corneal grafts.
Case 1
This is a penetrating keratoplasty (PK), ie a full thickness graft. I’ve photographed the periphery at low and medium power.
On low power, we can see that the epithelium is of irregular thickness and lifting off the underlying stroma, suggesting bullous keratopathy. There are fragments of suture material.
Annotated image:
green line = base of epithelium
yellow = suture material
On the medium power H&E, we can see a layer of retrocorneal fibrosis incorporating melanin pigment which is most likely from the iris. Endothelial cells are obliterated, which is why this graft failed.
Annotated image:
green = melanin
yellow = retrocorneal fibrosis
PAS stain shows fragmentation, folding and reduplication of Descemet’s membrane. The donor endothelium has laid down new Descemet’s membrane after the graft, but it’s rather disorganised. The peripheral portion of DM (patient’s native tissue) has small excrescences/warts. This far out, I wouldn’t make a diagnosis of Fuchs dystrophy.
Annotated image:
green = donor neo-Descemet’s membrane
yellow = host (patient) Descemet’s membrane
Case 2
This is a posterior lamella, ie a layer of posterior stroma plus Descemet’s membrane. Unsurprisingly, it’s thinner than the full thickness graft above. This graft was performed around 10 years ago, and it was a DLEK (deep lamellar endothelial keratoplasty) procedure. At that time, DLEKs were an improvement on PKs, maintaining better integrity of the globe.
Medium power shows relatively hypocellular stroma. I have an impression that posterior stroma is generally more compact than anterior stroma. Descemet’s membrane has come away from the posterior stroma, although this is probably artefactual. There are no endothelial cells.
Annotated image:
green = detached Descemet’s membrane
Case 3
And finally, here’s a folded sheet of PAS-positive basement membrane. This is Descemet’s membrane from a previous Descemet’s membrane endothelial keratoplasty (DMEK) procedure. This was a logical evolution of corneal grafts, with progressively thinner sheets being transplanted. Advantages include better integrity of the eye, less optical aberration, and less donor tissue to provoke rejection. Usual disclaimer: I am not a surgeon, so this is my simplistic take on the matter!
A higher power of the PAS stain shows the membrane to be of regular thickness.
If we look at an H&E-stained image, we can see a few endothelial cells, but not enough to maintain corneal transparency.
Annotated image:
green = the few surviving endothelial cells
yellow = if you’re new to microscopy, you might wonder what the orange blob is. This is artefactual. It’s someone’s skin squamous epithelial cell that landed on the slide while it was being prepared. It’s safe to ignore these!
These three cases are an illustration of how corneal graft surgery has evolved over the years.
Further reading
If you’re interested in reading around the topic, I’ve gathered a few open access papers here to give you a start. Papers are ordered by publication date.
Recent advances in keratoplasty by Ainslie (1974) might be of historical interest.
Endothelial Keratoplasty: From DLEK to DMEK by Fernandez and Afshari (2010) looks at the history of posterior corneal transplantaion.
A new era in corneal transplantation: paradigm shift and evolution of techniques by Young et al (2012) gives an overview of the different surgical techniques from a Hong Kong perspective. There are some nice diagrams illustrating the anatomy.
Graft Survival and Endothelial Outcomes in the New Era of Endothelial Keratoplasty by Patel (2014) addresses the following question: since endothelial keratoplasty requires more surgical manipulation of donor tissue, is there a risk of higher endothelial loss as compared to penetrating keratoplasty?
Component corneal surgery: An update by Maharana et al (2017) gives a comprehensive overview of the different surgical approaches for both anterior and posterior grafts.
Immune reactions after modern lamellar (DALK, DSAEK, DMEK) versus conventional penetrating corneal transplantation by Hos et al (2019) gives an overview of techniques as well as a review of immunological factors in graft rejection.
And on a final note, our postponed 2020 meeting of the British Association for Ophthalmic Pathology is being held online next week, on Friday 23 April. It’s free to attend. You can sign up here.
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