What are today’s ophthalmologists failing to notice when it comes to disease etiologies and processes? Or, as Gerrit R.J. Melles, MD, PhD, put it, “If a skilled ophthalmologist like Professor Ernst Fuchs ‘missed’ the endothelium in the early 1900s, what structure or mechanism do we fail to recognize today?”
Dr. Melles, a pioneer in corneal transplant procedures, posed that question during the Opening Session on Friday in his Jackson Memorial Lecture, “How Would Nature See Our Corneal Triumphs?” And as he referred to the potential gulf between widely accepted current clinical theories and the ever-unfolding array of clinical observations, he asked, “What is staring us in the face, but goes by unnoticed?”
Cornea conundrums. For instance, said Dr. Melles, the standard description of corneal hydration holds that active outflow occurs through the endothelial cell pump, creating a negative pressure within the corneal stroma—and, in turn, this allows for passive leakage of aqueous from the anterior chamber into the cornea. However, Dr. Melles said, clinical observation suggests the presence of a combined dynamic-static hydration pathway that consists of a horizontal flow of nutrients and depositions running parallel with the lamellae and collagen fibers.
Such an alternative mechanism would form a “more efficient and better fitting perfusion system for several reasons,” he said. “First, it would allow for all anterior to posterior corneal layers to be perfused homogeneously.” In addition, he said, “Instead of an indirect route through the anterior chamber, nutrients and other relevant factors would originate directly from the limbal vasculature, the main regenerative area of the cornea.”
Extending the hypothesis. If the “circular endothelial flow mechanism” is dismissed in favor of a horizontal pathway, then what role does the endothelium play in hydration?
One clue may be found in eyes with a partial endothelium. “Say that one-third of the endothelial surface area is missing due to inadvertent Descemet membrane detachment after phacoemulsification or a partial DMEK graft detachment,” Dr. Melles said. Theoretically, the entire cornea should go opaque because of massive influx of aqueous into the stroma. But as Dr. Melles pointed out, “Surprisingly, the edema is always confined to the area overlying the defective Descemet membrane.”
A series of additional clinical observations has led him to a working hypothesis that the endothelium may help regulate the imbibition pressure by stabilizing the hydration of the mucopolysaccharide rods that run from the posterior to the anterior cornea and are perpendicular to the corneal surface. He added that this would secure corneal transparency, “potentially depending on a single control mechanism shared by the imbibition and intraocular pressures.”
Future research directions. “Clinical observation may suggest that corneal nutrition, hydration, and transparency must stem from a far more sophisticated system than that currently described in the literature,” Dr. Melles said.
He suggested a number of hypotheses that are ripe for future research, including the possibility that Fuchs dystrophy may offer a key to the etiology of primary open-angle glaucoma (POAG). In particular, he noted that POAG and Fuchs dystrophy may be “remedy responses to a factor that triggers an overreaction without inflammation, possibly a factor that disrupts a steroid hormone balance.”
Going forward, he said, “We may have to look differently at the anterior segment of the eye, as Fuchs dystrophy could reflect ‘corneal glaucoma.’ Disorders now perceived as separate disease entities may be codependent or overlapping, originating from the same root cause in or outside the eye.
—Jean Shaw
Financial disclosures: Dr. Melles: SurgiCube International: C.
Disclosure key: C = Consultant/Advisor; E = Employee; EE = Employee, executive role; EO = Owner of company; I = Independent contractor; L = Lecture fees/Speakers bureau; P = Patents/Royalty; PS = Equity/Stock holder, private corporation; S = Grant support; SO = Stock options, public or private corporation; US = Equity/Stock holder, public corporation For definitions of each category, see
aao.org/eyenet/disclosures.
Learn more about Dr. Melles. Read the profile of Dr. Melles that was published in the Friday/Saturday edition of AAO 2022 News, the newspaper distributed at the convention center.
Read more news about Subspecialty Day and AAO 2022.