Corneal dystrophies are inherited disorders of the cornea, and most subtypes have an identified or suspected genetic cause, although the specific gene differs from one subtype to another. Because corneal dystrophy is an umbrella diagnosis covering many distinct conditions, the underlying biology is heterogeneous, with separate dystrophies arising from changes in genes that affect different proteins of the corneal epithelium, basement membrane, stromal extracellular matrix, or endothelium. Patterns of inheritance differ by subtype: many anterior and stromal forms follow an autosomal dominant pattern, several endothelial dystrophies show autosomal dominant or, less often, autosomal recessive inheritance, and rare X-linked forms have been reported. In some forms, particularly later-onset endothelial dystrophies, complex genetic and environmental factors are believed to contribute, and a proportion of individuals do not have a single clearly identified pathogenic variant. Identifying the specific subtype is important for understanding inheritance and recurrence risk, and genetic counseling is recommended when a familial pattern is suspected.

Diagnosis of corneal dystrophy begins with a comprehensive ophthalmic evaluation by an ophthalmologist, typically a corneal subspecialist, based on the clinical pattern of corneal findings together with family history. Slit-lamp biomicroscopy is the cornerstone examination and allows the clinician to characterize the location, depth, and shape of corneal opacities and to assign the changes to a specific layer of the cornea. Corneal imaging plays a central role and may include anterior segment optical coherence tomography to map opacity depth and corneal thickness, specular and confocal microscopy to assess endothelial cell density and morphology, and corneal topography or tomography to quantify shape and irregular astigmatism. Where the diagnosis or subtype is uncertain, targeted molecular genetic testing of corneal dystrophy genes can confirm a specific dystrophy and clarify inheritance and recurrence risk for the family. Symptoms of corneal dystrophy can overlap with other conditions, and genetic testing is required in many cases to confirm the diagnosis and distinguish it from conditions with similar presentations, including keratoconus and acquired corneal disease.

There is no therapy that prevents the underlying genetic basis of corneal dystrophy, and current management is directed at preserving vision, controlling symptoms, and addressing complications. For mild or early disease, observation with regular eye examinations may be all that is required. Recurrent corneal erosions are commonly managed with lubricating drops and ointments, hypertonic saline, bandage contact lenses, and, for refractory cases, surface procedures such as anterior stromal puncture or phototherapeutic keratectomy. For more advanced disease, partial or full-thickness corneal transplantation is the principal definitive treatment, with the choice between deep anterior lamellar keratoplasty for stromal disease, endothelial keratoplasty procedures such as Descemet membrane endothelial keratoplasty for endothelial dystrophies, and penetrating keratoplasty for full-thickness involvement. Post-transplant care includes topical corticosteroids and surveillance for graft rejection. Multidisciplinary care with a cornea specialist, optometrist, and primary eye care provider is recommended. Regular surveillance is an essential part of long-term care, helping to identify potential complications before they become serious. Several investigational therapies, including approaches under investigation for Fuchs endothelial corneal dystrophy and for prevention of corneal graft rejection, are in clinical development. Patients should discuss treatment options with their healthcare team to determine which therapies may be appropriate for their specific situation.

The outlook for individuals with corneal dystrophy depends strongly on the specific subtype, the corneal layer involved, and the rate of progression, and varies considerably from one person to another. Many forms progress slowly over years to decades, and useful vision can often be preserved with appropriate optical correction, lubrication, and management of recurrent erosions. When vision is significantly affected, modern corneal transplantation procedures, particularly endothelial keratoplasty for endothelial dystrophies, can substantially improve visual acuity, although recurrence of the underlying dystrophy in the graft has been reported in some forms over time. Coordinated care with a cornea specialist and timely intervention when symptoms progress allow most individuals to maintain functional vision and quality of life over the long term.

Research in corneal dystrophy is active, and several clinical studies are underway across the spectrum of corneal layer involvement. Ongoing research includes a Phase 2 trial of an investigational small-molecule therapy in keratoplasty patients with Fuchs endothelial corneal dystrophy sponsored by Design Therapeutics, a study evaluating reactive oxygen species as a therapeutic target in Fuchs endothelial corneal dystrophy at Massachusetts Eye and Ear, and procedural and surgical studies of endothelial keratoplasty techniques and outcomes at academic eye centers in Europe and the United States. National Eye Institute genotyping and phenotyping efforts are also enrolling individuals with rare inherited ophthalmic diseases, including the corneal dystrophies, to support gene discovery and clinical correlation. Individuals interested in clinical trials can search ClinicalTrials.gov or consult their care team about eligibility.