FECD reflects progressive dysfunction and loss of corneal endothelial cells, which normally pump fluid out of the cornea and keep it transparent. When endothelial cell density falls below a critical threshold, fluid builds up in the cornea and produces the swelling and cloudiness that drive vision loss. The underlying biology is incompletely understood and appears to involve cellular stress responses, abnormalities of the extracellular matrix that produce guttae, and accelerated endothelial cell loss with age. Most cases are sporadic, while a subset of families show an autosomal dominant pattern in which a single copy of a predisposing change can pass from an affected parent to a child. The specific genetic basis is still under investigation in this packet, and several recognized FECD subtypes have been mapped in the medical literature.

FECD is diagnosed by an ophthalmologist or cornea specialist through a combination of clinical examination and corneal imaging. Slit-lamp examination identifies the characteristic guttae on the inner cornea and any associated swelling. Specular microscopy and confocal microscopy provide direct images of the endothelial cell layer and allow clinicians to estimate cell density and the size of the guttae. Pachymetry measures corneal thickness, which tends to increase as fluid accumulates, and Scheimpflug or anterior segment optical coherence tomography can detect early changes in corneal shape and posterior surface contour. Symptoms can overlap with other causes of corneal edema, including pseudophakic bullous keratopathy, posterior polymorphous corneal dystrophy, and post-surgical endothelial decompensation, so careful clinical evaluation is needed to distinguish these conditions. In selected cases, molecular genetic testing may be considered, particularly when there is a strong family history.

There are no medicines specifically approved by the United States Food and Drug Administration to slow or reverse the underlying endothelial cell loss in FECD, so management focuses on relieving symptoms and restoring visual clarity. Foundational care for early disease typically involves hypertonic saline eye drops or ointment, which help draw fluid out of the cornea and reduce morning blurring. As the cornea fails to stay clear despite these measures, surgical options become the main avenue for restoring vision. Endothelial keratoplasty procedures, including Descemet membrane endothelial keratoplasty and Descemet stripping automated endothelial keratoplasty, replace only the diseased endothelial layer with healthy donor tissue and have largely replaced full-thickness corneal transplantation as the standard of care. In selected patients with a healthy peripheral endothelium, Descemet stripping only may allow the patient's own remaining cells to repopulate the central cornea. Regular surveillance with a cornea specialist is an essential part of long-term care, since disease progression can be slow and the timing of surgery is individualized.

The course of FECD varies widely. Many people live for years with mild guttae and minimal visual symptoms, while others progress to significant corneal swelling and vision loss that limits driving, reading, and night activities. Outcomes after modern endothelial keratoplasty are generally favorable, with most patients regaining functional vision, although graft survival, possible rejection, and the need for repeat procedures remain considerations over the long term. Because FECD is a slowly progressive condition that primarily affects the eye, it does not typically shorten life expectancy, and overall outcomes are improving with advances in surgical technique and donor tissue preparation.

Research in FECD is active, with work directed at refining endothelial transplantation, evaluating cell-based therapies that aim to regenerate the endothelium, exploring small molecules and gene-targeted approaches intended to slow endothelial cell loss, and validating imaging biomarkers. Several clinical trials are underway at academic centers and biotechnology companies. One investigational cell-based product carries an orphan drug designation from the FDA, which recognizes development for a rare condition but is not the same as marketing approval. Individuals interested in clinical trials can search ClinicalTrials.gov or consult their care team.