Fuchs Endothelial Corneal Dystrophy (FECD) is a disease primarily affecting the posterior (innermost) surface of the cornea, including the single layer of corneal endothelial cells and the membrane upon which they are arrayed, known as Descemet’s membrane. Although among the most common forms of corneal dystrophy, FECD is still rare within the general population with an estimated prevalence of 4-7%. Nonetheless, FECD is the leading indication for corneal transplant in the United States.
Although FECD exists in both an early- and late-onset form, the latter predominates by far. It can be identified in a pre-symptomatic phase in the third to fourth decade of life, with symptoms becoming apparent over the next one to two decades. Symptoms are often progressive, although at variable rates among affected patients. If left untreated, in a number of patients progression can lead to corneal decompensation and visual loss. Although the reasons for the variation in symptomatic progression are unclear, it is known that FECD features a complex genetic basis. Even among patients with a known family history of FECD, its clinical “expressivity” in affected individuals can vary. Further, by some estimates as many as half of cases are non-inherited and most patients are unaware of a family history. Moreover, it is speculated that various environmental factors may contribute to its clinical severity.
The corneal endothelial cell layer is responsible for maintaining an appropriate level of hydration throughout corneal tissue. In patients with FECD, corneal endothelial cells are affected both quantitatively (accelerated cell loss) and qualitatively (diminished cell function) over time, so that the remaining layers of the cornea progressively swell, leading to visual impairment. Additionally, Descemet’s membrane is diseased in FECD, developing abnormalities known as “guttae,” or “guttata,” which also contribute to visual impairment and are often the first abnormal findings on examination of patients with FECD.
Patients with symptomatic FECD generally describe visual changes such as blurring, haloing around bright lights, and diminished contrast and color vibrancy. In early stages of FECD, these are mild and most noticeable in the morning. As the disease progresses, symptoms can worsen and become persistent throughout the day. Patients may develop a deteriorating visual quality of life and important activities of daily living such as driving, especially in the dark, and reading can become affected. Eventually, the full thickness of cornea can swell to the point of developing painful blisters and scarring. At this point, the benefit of surgical treatment becomes less predictable.
In its early stages, patients with mild FECD can take advantage of medical treatments such as concentrated saline eye drops that can help alleviate symptoms. As the disease advances, however, these become ineffective and surgery becomes the definitive treatment.
Enormous advances have been made in the surgical approaches to FECD over many decades’ time. Transplantation of donor cornea tissue, known as “keratoplasty,” has evolved from the original use of full-thickness cornea which was the standard for much of the twentieth century. This technique, known as “penetrating keratoplasty,” yielded variable results in terms of visual outcome, required a prolonged time to achieve adequate healing, and was fraught with a high incidence of complications including infection and tissue rejection. However, the past twenty-five years have witnessed a rapid evolution in keratoplasty techniques with increasingly refined focus on the specific microscopic layers of tissue involved in the disease process. In the case of FECD, this includes only the endothelial cells and the Descemet membrane, and the most recent innovation in keratoplasty, Descemet Membrane Endothelial Keratoplasty (“DMEK”), which includes only these layers, has become regarded as the current gold standard in corneal tissue transplant for FECD. It yields excellent visual outcome, with rapid healing and very low incidence of rejection, especially with ongoing use of steroid eye drops.
However, all forms of keratoplasty involve transplantation of donor tissue and carry some degree of risk, even if quite low in the case of DMEK (and its predecessor, “DSAEK”). Thus, the most recent surgical approach to the treatment of FECD, known as Descemet Stripping Only (“DSO,”) relies on the removal of diseased endothelial cells from the center, and most visually important area, of the posterior corneal surface with the expectation that cells from the periphery will migrate and repopulate the central region. DSO is thus the first technique which eliminates the need for transplantation of donor tissue and, if proven successful in terms of benefit vs risk, and given a sufficient track record over time, may eventually compete with DMEK as the standard of care in FECD. Although many patients who have undergone this procedure have had successful, satisfying results, it is estimated that, as of early 2024, fewer than one thousand patients have undergone DSO worldwide and DSO is thus considered an emerging approach. Although it has considerable promise, a proven, medically substantiated benefit of DSO will require rigorous study to generate a statistically valid volume of data for analysis as well as copious experience among surgeons and patients.
