Posterior amorphous corneal dystrophy (PACD) is a rare corneal dystrophy affecting the posterior corneal stroma, Descemet’s membrane, and occasionally the iris. It is classified as a stromal corneal dystrophy in the IC3D classification 1). It follows an autosomal dominant inheritance pattern and presents bilaterally.
The characteristic finding of this disease is bilateral sheet-like posterior stromal opacities. It is accompanied by corneal flattening and thinning, and the flattening of the corneal surface shifts the refractive state toward hyperopia. Onset can occur as early as 16 weeks of age, but typically within the first 10 years of life, suggesting a congenital nature.
The disease is usually slowly progressive or non-progressive, and its impact on vision is often minimal.
ICD-10 codes: H18.593, H18.599.
QHow is PACD different from acquired corneal diseases?
A
PACD is a hereditary corneal dystrophy caused by a gene deletion on chromosome 12q21.33, leading to developmental abnormalities in the posterior corneal stroma and Descemet’s membrane. Its etiology is fundamentally different from acquired corneal diseases such as pterygium or band keratopathy, which are caused by environmental factors. See Pathophysiology and Detailed Mechanism for details.
Patients with PACD are usually asymptomatic. Hyperopia due to corneal flattening may be the only refractive error. Visual changes are mild and rarely interfere with daily life.
Sheet-like posterior stromal opacity: Large amorphous sheet-like opacities in the posterior corneal stroma and Descemet’s membrane. Bilateral, pathognomonic for PACD.
Corneal thinning: Associated with decreased corneal thickness.
Corneal flattening: Corneal curvature becomes flatter, leading to hyperopia.
Iris abnormalities: May be accompanied by extra-corneal findings such as iridocorneal adhesions, corectopia, and pseudopolycoria.
PACD follows an autosomal dominant inheritance pattern. The causative gene locus has been reported to be associated with a contiguous gene deletion on chromosome 12q21.33. This region contains four genes encoding small leucine-rich proteoglycans (SLRPs).
Gene
Encoded Protein
Associated Disease
KERA
Keratocan
Flat cornea (AR)
LUM
Lumican
—
DCN
Decorin
Congenital stromal dystrophy
EPYC
Epiphycan
—
These proteins are involved in collagen fibril formation and matrix construction, which are essential for maintaining corneal transparency. It is thought that a combination of deletions in four SLRP genes causes impairment of corneal transparency.
Family history: Since it is an autosomal dominant disorder, first-degree relatives of an affected individual have a 50% chance of carrying the mutation.
To date, no prevention strategies based on environmental factors have been studied.
Slit-lamp microscopy: Confirms sheet-like opacities in the posterior stroma and Descemet’s membrane. Evaluates the presence of corneal thinning and flattening. This is the basic examination for clinical diagnosis.
Confocal microscopy: May reveal microfolds or hyperreflective layers in the posterior stroma adjacent to the endothelial layer.
Clinical diagnosis is based on the characteristic diffuse sheet-like posterior stromal opacity observed on slit-lamp microscopy and a positive family history.
Macular corneal dystrophy: AR inheritance. Abnormal keratan sulfate synthesis. Progressive with significant visual impairment. May involve thinning but progresses unlike PACD.
Speckled corneal dystrophy: AD inheritance. PIKFYVE mutation. Small dandruff-like opacities scattered in the stroma. No sheet-like opacities or corneal flattening.
Schnyder corneal dystrophy: AD inheritance. UBIAD1 mutation. Cholesterol deposition. Unlike PACD, opacities are progressive.
Abnormalities of Posterior Stroma and Descemet's Membrane
Lattice corneal dystrophy type 1: TGFBI mutation. Linear opacities due to amyloid deposition. Localized thinning of Bowman’s layer is present, but no overall corneal thinning or flattening.
QCan PACD be definitively diagnosed by genetic testing?
A
Deletion of the SLRP gene cluster (KERA, LUM, DCN, EPYC) on chromosome 12q21.33 is associated with PACD, but it is not established which gene or combination of genes is essential for the pathology. Currently, clinical diagnosis (slit-lamp microscopy findings + family history) is the mainstay, and genetic testing is supplementary.
PACD is usually non-progressive and does not require treatment. Explain to the patient that there is no risk of malignancy and perform regular follow-up.
In some cases, the opacity progresses and spreads throughout the corneal stroma, leading to decreased vision. When visual impairment becomes significant, full-thickness corneal transplantation (penetrating keratoplasty) is indicated.
If donor cornea is not available, superficial keratectomy may be considered as a temporary measure.
QCan PACD be cured by corneal transplantation?
A
Full-thickness corneal transplantation can replace the opaque cornea, but since PACD is a hereditary disease, there is a possibility of recurrence in the graft. Corneal transplantation is indicated only for advanced cases with significant visual impairment; most patients can be managed with observation alone.
Genome-wide linkage analysis of families with a history of PACD has shown linkage to the chromosome 12q21.33 region. This region contains four SLRP genes: keratocan (KERA), lumican (LUM), decorin (DCN), and epiphycan (EPYC).
SLRPs are involved in collagen fiber formation and matrix construction. Mutations in individual SLRP genes are known to cause different corneal diseases. Mutations in KERA are associated with autosomal recessive flat cornea, and nonsense mutations in DCN are associated with congenital hereditary stromal dystrophy. In PACD, deletions of these four genes are presumed to act in combination, but which gene is essential has not been determined.
Examination of corneal buttons from PACD patients who underwent full-thickness penetrating keratoplasty has reported the following findings:
Light microscopy: Disruption of the posterior stromal collagen lamellae and focal reduction of corneal endothelial cells. No edema, inflammation, or neovascularization is present. Descemet’s membrane is uniformly thin, without irregular folds or thickening.
Electron microscopy: Disorganization of collagen fiber arrangement in the posterior stromal lamellae and loss of endothelial cells.
These findings indicate developmental abnormalities in the formation of the posterior stroma and Descemet’s membrane in PACD. Colloidal iron staining shows positive findings in the posterior stroma, suggesting abnormal accumulation of glycosaminoglycans.
American Academy of Ophthalmology Corneal/External Disease Preferred Practice Pattern Panel. Corneal Edema and Opacification Preferred Practice Pattern. San Francisco: AAO; 2024.
Copy the article text and paste it into your preferred AI assistant.
Article copied to clipboard
Open an AI assistant below and paste the copied text into the chat box.
