ESCRS - Rethinking Fuchs' Dystrophy ;
ESCRS - Rethinking Fuchs' Dystrophy ;

Rethinking Fuchs' Dystrophy

New ideas on its aetiology, characteristic features, and relationship with POAG.

Rethinking Fuchs' Dystrophy
Cheryl Guttman Krader
Cheryl Guttman Krader
Published: Thursday, March 2, 2023
“ Fuchs’ dystrophy should not be considered an endothelial disease; instead, it may be a mucopolysaccharide disorder. “

Renowned cornea specialist Gerritt RJ Melles MD, PhD was having difficulty reconciling teachings found in textbooks with clinical observations regarding corneal perfusion and hydration mechanisms, the corneal endothelium’s role in maintaining stromal imbibition pressure, and the aetiology of primary open-angle glaucoma (POAG) development.

In the 79th Jackson Memorial Lecture delivered at the American Academy of Ophthalmology annual meeting, he proposed Fuchs’ dystrophy should not be considered an endothelial disease. Instead, he suggested it may be a mucopolysaccharide disorder.

Dr Melles also speculated similarities in the pathogenesis of POAG and Fuchs’ dystrophy, wherein both might develop as remedy responses to some factor that triggers an overreaction without inflammation. Proposing Fuchs’ dystrophy is characterised by an imbibition pressure level that is too high (too negative), he introduced the idea it may actually be a “corneal glaucoma.”

“Reframing Fuchs’ dystrophy in this different way might actually be the gateway to understanding POAG aetiology,” Dr Melles said.

He reviewed several clinical situations that are inconsistent with the concept that corneal physiology and nutrition are maintained via a localised fluid circulation over the endothelial cell layer in which there is active outflow through the endothelial cell pump that creates a negative imbibition pressure within the corneal stroma that in turn allows for passive leakage of aqueous into the cornea.

“It seems a very ineffective way to perfuse the cornea,” he noted.

As an alternative, he proffered the existence of a much more sophisticated system to explain corneal nutrition, hydration, and transparency. He suggested combined dynamic and static flow mechanisms—described respectively by horizontal perfusion from the limbal vascular arcade into the cornea—provide nutrition regardless of the endothelial condition and vertical control of imbibition pressure, maintaining transparency and involving the mucopolysaccharide rods that run throughout the cornea to its surface.

Dr Melles presented new perspectives on the interaction between the cornea and IOP and the pathomechanism for POAG, starting with a consideration of the relationship between IOP and imbibition pressure.

He offered ideas to explain what he termed “the paradox of Fuchs’ dystrophy,” i.e., imbibition pressure is normal despite an absent or compromised endothelial layer and the mechanism for guttae formation.

“If there is a link between the imbibition pressure and IOP, there must be a similar feedback loop controlling them in a similar way,” Dr Melles said, tying the new perspectives together. “It would stand to reason that if we understand how the imbibition pressure is controlled, that may open the door to understanding how IOP is controlled and why you get POAG.”

As a caveat, however, he indicated at the start and the end of his lecture that his new ideas should not be considered the definitive word. He prefaced the material by noting that his presentation would include a lot of “buts, ifs, maybes, and things that are very speculative.”

Observing Professor Fuchs seemed to have “missed” the endothelium, Dr Melles asked, “What are we missing today that we will be mocked for in 100 years when they ask, ‘Why didn’t they think of … fill in the blank?’”

He invited attendees to access his complete essay describing his new perspectives in detail and the clinical observations on which they are based by visiting his organisation’s homepage at under JML lecture.

Gerritt RJ Melles MD, PhD is Director, Netherlands Institute for Innovative Ocular Surgery, Rotterdam, Netherlands.

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